RARE HEMATOLOGICAL TUMORS AND SYNDROMES

Diagnosis of EBV-Associated Inflammatory Pseudotumor in the Spleen: A Case Report

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , , ,

DI Chebotarev, AM Kovrigina, SM Korzhova, KI Danishyan, KR Sabirov

National Medical Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Dmitrii Il’ich Chebotarev, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(916)091-27-09; e-mail: chebadmitry@gmail.com

For citation: Chebotarev DI, Kovrigina AM, Korzhova SM, et al. Diagnosis of EBV-Associated Inflammatory Pseudotumor in the Spleen: A Case Report. Clinical oncohematology 2019;12(4):428–33 (In Russ).

DOI: 1021320/2500-2139-2019-12-4-428-433

ABSTRACT

The paper focuses on Epstein-Barr virus (EBV)-associated inflammatory pseudotumor in the spleen, an extremely rare disease which so far remained undefined in the Russian literature. The morphology of it is not characterized by any specific features and is represented by a spindle-cell component with pronounced inflammatory infiltration which complicates differential diagnosis. Previously this nosology was regarded within a group of the so-called inflammatory pseudotumors due to the similarity of the clinical course and radiological presentation with tumor processes. Today the term “inflammatory pseudotumor” is considered obsolete, since as pathogenesis was being studied within this disease group, the individual forms with similar morphology and different histogenesis were identified. Differential diagnosis in the context of additional diagnostic techniques is based in such cases on a wide range of reactive states, benign and malignant tumors.

Keywords: inflammatory pseudotumor, inflammatory myofibroblastic pseudotumor, EBV-associated inflammatory pseudotumor in the spleen, IgG4-associated diseases, variant of follicular dendritic cell sarcoma similar to inflammatory pseudotumor.

Received: May 19, 2019

Accepted: September 15, 2019

Read in PDF

REFERENCES

  1. Bhaskar S, Levin M, Frish J. Plasma cell granuloma of periodontal tissues. Report of 45 cases. Periodontics. 1968;6(6):272–6.

  2. Mason WE, Keats TE, Baker GF. Inflammatory pseudotumor of the lung. Radiology. 1963;81(5):824–7. doi: 10.1148/81.5.824.

  3. Herczeg E, Weissberg D, Almog C, Pajewski M. Inflammatory fibrous histiocytoma of the bronchus. Chest. 1978;73(5):669–70. doi: 10.1378/chest.73.5.669.

  4. Poleksic S, Kalwaic HJ, Bialas RF. Benign atypical fibroxanthoma or a malignant tumor? A warning. Case reports. Plast Reconstr Surg. 1976;58(4):501–5. doi: 10.1097/00006534-197610000-00024.

  5. Forster R, Ruschoff J, Kleinsorge F. Retroperitoneal xanthofibrogranulomatosis. RoFo. 1989;151(12):688–91. doi: 10.1055/s-2008-1047268.

  6. Greenberg SD, Jenkins DE. Xanthomatous inflammatory pseudotumor of the lung. South Med J. 1975;68(6):754–6. doi: 10.1097/00007611-197506000-00025.

  7. Pisciotto PT, Gray GF Jr, Miller DR. Abdominal plasma cell pseudotumor. J Pediatr. 1978;93(4):628–30. doi: 10.1016/s0022-3476(78)80903-2.

  8. Sherwin RP, Kern WH, Jones JC. Solitary mast cell granuloma (histiocytoma) of the lung; a histopathologic, tissue culture and time-lapse cinematographic study. Cancer. 1965;18(5):634–41. doi: 10.1002/1097-0142(196505)18:5%3C634::aid-cncr2820180512%3E3.0.co;2-k.

  9. Coffin CM, Dehner LP, Meis-Kindblom JM. Inflammatory myofibroblastic tumor, inflammatory fibrosarcoma, and related lesions: an historical review with differential diagnostic considerations. Semin Diagn Pathol. 1998;15(2):102–10.

  10. Brunn H. Two interesting benign lung tumours of contradictory histopathology: remarks on the necessity for maintaining the chest tumour registry. J Thorac Cardiovasc. 1939;9:119–31.

  11. Umiker WO, Iverson LC. Post inflammatory tumor of the lung: report of four cases simulating xanthoma, fibroma or plasma cell granuloma. J Thorac Surg. 1954;28(1):55–63.

  12. Lakshmana DN, Beverley N, Stephanie SS, et al. Inflammatory Pseudotumor. RadioGraphics. 2003;23(3):719–29. doi: 10.1148/rg.233025073.

  13. Patnana M, Sevrukov AB, Elsayes KM, et al. Inflammatory Pseudotumor: The Great Mimicker. Am J Roentgenol. 2012;198(3):W217–W227. doi. 10.1111/j.1440-1827.2010.02556.x.

  14. Bosse K, Ott C, Biegner T, et al. 23-year-old female with an inflammatory myofibroblastic tumour of the breast: a case report and a review of the literature. Geburtshilfe Frauenheilkunde. 2014;74(02):167–70. doi: 10.1055/s-0033-1360185.

  15. Santaolalla-Montoya F, Ereno C, Zabala A, et al. Inflammatory myofibroblastic tumor of the temporal bone: a histologically nonmalignant lesion with fatal outcome. Skull Base. 2008;18(05):339–43. doi: 10.1055/s-0028-1086060.

  16. Oh JH, Yim JH, Yoon BW, et al. Inflammatory pseudotumor in the mandible. J Craniofac Surg. 2008;19(6):1552–3. doi: 10.1097/scs.0b013e318188a2e9.

  17. Williamson RA, Paueksakon P, Coker NJ. Inflammatory pseudotumor of the temporal bone. Otol Neurotol. 2003;24(5):818–82. doi: 10.1097/00129492-200309000-00021.

  18. Yuan XP, Li CX, Cao Y, et al. Inflammatory myofibroblastic tumour of the maxillary sinus: CT and MRI findings. Clin Radiol. 2012;67(12): e53–e57. doi: 10.1016/j.crad.2012.08.002.

  19. Masciocchi C, Lanni G, Conti L, et al. Soft-tissue inflammatory myofibroblastic tumors (IMTs) of the limbs: Potential and limits of diagnostic imaging. Skelet Radiol. 2012;41(6):643–9. doi: 10.1007/s00256-011-1263-7.

  20. Lin J, Liu H, Zhuang Y, et al. Inflammatory myofibroblastic tumor of the thigh without bone involvement: a case report. World J Surg Oncol. 2014;12(1):208. doi: 10.1186/1477-7819-12-208.

  21. Sanders BM, West KW, Gingalewski C, et al. Inflammatory pseudotumor of the alimentary tract: clinical and surgical experience. J Pediatr Surg. 2001;36(1):169–73. doi: 10.1053/jpsu.2001.20045.

  22. Gong S, Auer I, Duggal R, et al. Epstein-Barr virus-associated inflammatory pseudotumor presenting as a colonic mass. Hum Pathol. 2015;46(12):1956–61. doi: 10.1016/j.humpath.2015.08.011.

  23. Rosenbaum L, Fekrazad MH, Rabinowitz I, Vasef MA. Epstein-Barr virus-associated inflammatory pseudotumor of the spleen: report of two cases and review of the literature. J Hematop. 2009;2(2):127–31. doi: 10.1007/s12308-009-0030-3.

  24. Kim HJ, Kim JE, Kang GH, et al. Inflammatory Pseudotumor-like Follicular Dendritic Cell Tumor of the Spleen with Extensive Histiocytic Granulomas and Necrosis: A Case Report and Literature Review. Korean J Pathol. 2013;47(6):599–602. doi: 10.4132/KoreanJPathol.2013.47.6.599.

  25. Cook JR, Dehner LP, Collins MH, et al. Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study. Am J Surg Pathol. 2001;25(11):1364–71. doi: 10.1097/00000478-200111000-00003.

  26. Lawrence B, Perez-Atayde A, Hibbard MK, et al. TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. Am J Pathol. 2000;157(2):377–84. doi: 10.1016/S0002-9440(10)64550-6.

  27. Della-Torre E, Lanzillotta M, Doglioni C. Immunology of IgG4-related disease. Clin Exp Immunol. 2015;181(2):191–206. doi: 10.1111/cei.12641.

  28. Lu Y, Li L, Bhat R, Hou JS. IgG4-Related Lesion in Spleen: Sclerosing Angiomatoid Nodular Transformation of the Spleen. Am J Clin Pathol. 2018;150(Suppl 1):S93. doi: 10.1093/ajcp/aqy097.223.

  29. Патологическая анатомия: атлас. Под ред. О.В. Зайратьянца. М.: ГЭОТАР-Медиа, 2012. 960 с.

    [Zairat’yants OV, ed. Patologicheskaya anatomiya: atlas. (Atlas of anatomic pathology.) Moscow: GEOTAR-Media Publ.; 960 p. (In Russ)]

A Case of M-Paraprotein-Associated Polyneuropathy with Stable Response to Rituximab Therapy

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , ,

VG Potapenko1,3, VN Kiselev2

1 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

2 AM Nikiforov Russian Center of Emergency and Radiation Medicine, 4/2 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

3 IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Vsevolod Gennad’evich Potapenko, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110; Tel.: +7(905)284-51-38; e-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Kiselev VN. A Case of M-Paraprotein-Associated Polyneuropathy with Stable Response to Rituximab Therapy. Clinical oncohematology. 2019;12(4):434–7 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-434-437

ABSTRACT

Monoclonal gammopathy of undetermined significance is diagnosed on the basis of an extensive search for a diagnostic reason as paraprotein secretion occurs in different diseases. One of polyneuropathies associated with M-paraproteinemia is anti-MAG demyelinating polyneuropathy (AMDP). The first-line treatment of this disease is based on prednisolone, and intravenous immunoglobulin. The second-line therapy of treatment-resistant patients is not determined. We report a case of a female patient with AMDP who received prednisolone, azathioprine, and plasmapheresis; however, stable response was reached only after the use of rituximab.

Keywords: paraprotein, monoclonal gammopathy of undetermined significance (MGUS), myelin-associated glycoprotein (MAG), polyneuropathy, rituximab.

Received: January 22, 2019

Accepted: September 5, 2019

Read in PDF

REFERENCES

  1. Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346(8):564–9. doi: 10.1056/NEJMoa01133202.

  2. Гинзберг М.А., Варламова Е.Ю., Рыжко В.В. и др. Клинико-нейрофизиологическое исследование хронической демиелинизирующей полиневропатии, ассоциированной с моноклональной секрецией. Медицинский совет. 2015;10:93–6.

    [Ginzberg MA, Varlamova EYu, Ryzhko VV, et al. Clinical and neurophysiological study of chronic demyelinating polyneuropathy associated with monoclonal secretion. Meditsinskii sovet. 2015;10:93–6. (In Russ)]

  3. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – First Revision. J Peripher Nerv Syst. 2010;15(1):1–9. doi: 10.1111/j.1529-8027.2010.00245.x.

  4. Dalakas MC, Rakocevic G, Salajegheh M. Placebo-controlled trial of rituximab in IgM anti-myelin associated glycoprotein antibody demyelinating neuropathy. Ann Neurol. 2009;65(3):286–93. doi: 10.1002/ana.21577.

  5. Супонева Н.А., Павлов Э.В. Диагностика и базовая терапия хронических полиневропатий. Врач. 2009;4:43–4.

    [Suponeva NA, Pavlov EV. Diagnosis and basic therapy of chronic polyneuropathies. Vrach. 2009;4:43–4. (In Russ)]

  6. Яковлев А.А., Гапешин Р.А., Смочилин А.Г., Яковлева М.В. Оценка эффективности человеческого иммуноглобулина у пациентов с полинейропатией, ассоциированной с моноклональной гаммапатией неустановленной этиологии. Архивъ внутренней медицины. 2018;8(4):278–84. doi: 10.20514/2226-6704-2018-8-4-278-284.

    [Yakovlev AA, Gapeshin RA, Smochilin AG, Yakovleva MV. Evaluation of human immunoglobulin effectiveness in patients with sensorymotor polyneuropathy associated with monoclonal gammapathy of undetermined significance. The Russian Archives of Internal Medicine. 2018;8(4):278–84. doi: 10.20514/2226-6704-2018-8-4-278-284. (In Russ)]

  7. Comi G, Roveri L, Swan A, et al. A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy. J Neurol. 2002;249(10):1370–7. doi: 10.1007/s00415-002-0808-z.

  8. Lunn MP, Nobile-Orazio E. Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies. Cochrane Database Syst Rev. 2006;2:CD002827. doi: 10.1002/14651858.cd002827.pub2.

  9. Leger JM, Viala K, Nicolas G, et al. Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein neuropathy. Neurology. 2013;80(24):2217–25. doi: 10.1212/WNL.0b013e318296e92b.

  10. Gazzola S, Delmont E, Franques J, et al. Predictive factors of efficacy of rituximab in patients with anti-MAG neuropathy. J Neurol Sci. 2017;377:144–8. doi: 10.1016/j.jns.2017.04.015.

  11. Niermeijer JMF, Fischer K, Eurelings M, et al. Prognosis of polyneuropathy due to IgM monoclonal gammopathy: a prospective cohort study. Neurology. 2010;74(5):406–12. doi: 10.1212/wnl.0b013e3181ccc6b9.

  12. Nobile-Orazio E, Meucci N, Baldini L, et al. Long-term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies. Brain. 2000;123(4):710–7. doi: 10.1093/brain/123.4.710.

  13. Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350(25):2572–81. doi: 10.1056/nejmoa032534.

Paroxysmal Nocturnal Hemoglobinuria in Patients with Aplastic Anemia: Challenges, Characteristics, and Analysis of Clinical Experience

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , , , ,

ER Shilova1, TV Glazanova1, ZhV Chubukina1, OE Rozanova1, MN Zenina1, AV Seltser1, VI Rugal1, VA Balashova1, VA Kobilyanskaya1, II Krobinets1, VYu Udal’eva1, II Zotova1, LV Stelmashenko1, NA Romanenko1, TB Zamotina1, IV Khorsheva1, SV Voloshin1,2,3

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

2 SM Kirov Military Medical Academy, 6 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

3 II Mechnikov North-Western State Medical University, 41 Kirochnaya str., Saint Petersburg, Russian Federation, 191015

For correspondence: Elena Romanovna Shilova, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(981)129-09-77; e-mail: rniiht@mail.ru

For citation: Shilova ER, Glazanova TV, Chubukina ZhV, et al. Paroxysmal Nocturnal Hemoglobinuria in Patients with Aplastic Anemia: Challenges, Characteristics, and Analysis of Clinical Experience. Clinical oncohematology. 2019;12(3):319–28 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-319-328

ABSTRACT

Background & Aims. Paroxysmal nocturnal hemoglobinuria (PNH) is a disease caused by an acquired clonal disorder of hematopoietic stem cells with clone cell membrane hypersensitivity to the complement. PNH can exist as an independent disease and can also be associated with other pathological conditions characterized by bone marrow deficiency, first of all with aplastic anemia (AA). In PNH-associated AA (AA/PNH) pathological clones may be initially of different size. In some patients a gradual growth of PNH clone is observed together with occurring signs of intravascular hemolysis and transformation into classical hemolytic PNH. In this case it is important to assess the clinical situation and determine eligibility for complement inhibitor therapy. During targeted therapy it is necessary to assess the efficacy of treatment based on monitoring of complement-mediated hemolysis and to identify probable reasons for insufficient effect.

Materials & Methods. The paper deals with 1 clinical case. A female patient born in 1964, with initial diagnosis of AA was followed-up from 1989 till present at the Russian Research Institute of Hematology and Transfusiology. Her treatment included blood-component therapy, the use of antilymphocyte immunoglobulin, cyclosporine, plasmapheresis, eculizumab, and symptom-relieving drugs.

Results. The study deals with the case of transformation of non-severe AA with remission after immune-suppressive therapy into classical hemolytic PNH. The case report describes the characteristic features, AA/PNH diagnosis and treatment issues at different stages of the disease, and the reasons for incomplete effect of targeted therapy.

Conclusion. The case under discussion confirms the relevance of current methods of detecting PNH clone at early stages of AA diagnosis and dynamic follow-up with respect to a probable growth of clone with PNH phenotype, especially at the stage of hematopoietic recovery. Determination of PNH clone size and lactate dehydrogenase serum level is required for timely amendment of treatment strategy with a switch to long-term targeted monitoring of hemolysis which allows to prevent irreversible visceral changes and severe complications. In case of insufficient effect of targeted therapy with ongoing anemia Coombs test is recommended because of probability of C3-mediated extravascular hemolysis.

Keywords: aplastic anemia, paroxysmal nocturnal hemoglobinuria, PNH phenotype, PNH clone, targeted therapy, C3-mediated hemolysis.

Received: December 24, 2018

Accepted: May 29, 2019

Read in PDF 

REFERENCES

  1. Borowitz MJ, Craig FE, Digiuseppe JA, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry B Clin Cytom. 2010;78(4):211–30. doi: 10.1002/cyto.b.20525.

  2. Sutherland DR, Keeney M, Illingworth A. Practical guidelines for the high-sensitivity detection and monitoring of paroxysmal nocturnal hemoglobinuria clones by flow cytometry. Cytometry B Clin. Cytom. 2012;82(4):195–208. doi: 10.1002/cyto.b.21023.

  3. Kulagin A, Lisukov I, Ivanova M, et al. Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two-centre prospective study. Br J Haematol. 2014;164(4):546–54. doi: 10.1111/bjh.12661.

  4. Shilova ER, Glazanova TV, Chubukina ZV, et al. Aplastic anemia associated with PNH-clone – a single centre experience. Blood. 2016;128(22):5080.

  5. De Latour RP, Mary JY, Salanoubat C, et al. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood. 2008;112(8):3099–106. doi: 10.1182/blood-2008-01-133918.

  6. Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. 2013;121(25):4985–96. doi: 10.1182/blood-2012-09-311381.

  7. Shresenmeier H, Hertenstein B, Wagner B, et al. A patogenetic link between aplastic anemia and paroxysmal nocturnal haemoglobinuria is suggested by a high frequency of aplastic anaemia patients with a deficiency of phosphatidylinositol glycan anchored proteins. Exp Haematol. 1995;23(2):181.

  8. Wanachiwanawin W, Siripanyaphinyo U, Piyawattanasakul N, et al. A cohort study of the nature of paroxysmal nocturnal hemoglobinuria clones and PIG-A mutations in patients with aplastic anemia. Eur J Haematol. 2006;76(6):502–9. doi: 10.1111/j.0902-4441.2005.t01-1-EJH2467.x.

  9. Glazanova TV, Chubukina ZV, Rozanova OE, et al. Detection of PNH-clone in patients with depression of hemopoiesis. Haematologica. 2013;98(Suppl 1):579.

  10. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006;108(8):2509–19. doi: 10.1182/blood-2006-03-010777.

  11. Mortazavi Y, Merk B, McIntosh J, et al. The spectrum of PIG-A gene mutations in aplastic anaemia/paroxysmal nocturnal hemoglobinuria (AA/PNH): a high incidence of multiple mutation and evidence of mutational hot spot. Blood. 2003;101(7):2833–41. doi: 10.1182/blood-2002-07-2095.

  12. Кулагин А.Д., Лисуков И.А., Птушкин В.В. и др. Национальные клинические рекомендации по диагностике и лечению пароксизмальной ночной гемоглобинурии. Онкогематология. 2014;9(2):20–8. doi: 10.17650/1818-8346-2014-9-2-20-28.

    [Kulagin AD, Lisukov IA, Ptushkin VV, et al. National clinical guidelines for the diagnosis and treatment of paroxysmal nocturnal hemoglobinuria. 2014;9(2):20–8. doi: 10.17650/1818-8346-2014-9-2-20-28. (In Russ)]

  13. Kulagin A, Golubovskaya I, Ivanova M, et al. Incidence and risk factors for hemolytic paroxysmal nocturnal hemoglobinuria (PNH) in aplastic anemia (AA) patients. Bone Marrow Transplant. 2014;49(Suppl 1):S42–43.

  14. Lee JW, Jang JH, Kim JS, et al. Clinical signs and symptoms associated with increased risk for thrombosis in patients with paroxysmal nocturnal hemoglobinuria from a Korean Registry. Int J Hematol. 2013;97(6):749–57. doi: 10.1007/s12185-013-1346-4.

  15. Loshi M, Porcher R, Barraco F, et al. Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study. Am J Hematol. 2016;91(4):366–70. doi: 10.1002/ajh.24278.

  16. Kelly R, Hill A, Hillmen P, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011;117(25):6786–92. doi: 10.1182/blood-2011-02-333997.

  17. Nishimura J, Yamamoto M, Hayashi S, et al. Genetic variants in C5 and poor response to eculizumab. N Engl J Med. 2014;370(7):632–9. doi: 10.1056/NEJMoa1311084.

  18. Camitta BM, Rozman C, Marin P, et al. Criteria for severe aplastic anaemia. Lancet 1988;331(8580):303–4. doi: 10.1016/s0140-6736(88)90388-1.

  19. van Kamp H, van Imhoff G, de Wolf J, et al. The effect of cyclosporine on hematological parameters in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1995;89(1):79–82. doi: 10.1111/j.1365-2141.1995.tb08907.x.

  20. Лисуков И.А., Крючкова И.В., Кулагин А.Д. и др. Клинический случай пароксизмальной ночной гемоглобинурии с ответом на терапию циклоспорином А. Гематология и трансфузиология. 1998;43(5):45–6.

    [Lisukov IA, Kryuchkova IV, Kulagin AD, et al. Clinical case of paroxysmal nocturnal hemoglobinuria with response to cyclosporine A therapy. Gematologiya i transfuziologiya. 1998;43(5):45–6. (In Russ)]

  21. Подопригора Г.И., Андреев В.Н. Современные методы изучения фагоцитарной активности лейкоцитов in vitro. Журнал микробиологии, эпидемиологии и иммунологии. 1976;53(1):19–26.

    [Podoprigora GI, Andreev VN. Current methods of studying the phagocytic activity of leukocytes in vitro. Zhurnal mikrobiologii, epidemiologii i immunologii. 1976;53(1):19–26. (In Russ)]

  22. Hillmen P, Lewis SM, Bessler M, et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333(19):1253–8. doi: 10.1056/NEJM199511093331904.

  23. Hall SE, Rosse WF. The use of monoclonal antibodies and flow cytometry in the diagnosis of paroxysmal nocturnal hemoglobinuria. Blood. 1996;87(12):5332–40.

  24. Козлов Л.В. Исследование функциональной активности компонентов факторов системы комплемента человека. Вопросы медицинской химии. 2002;48(6):624–31.

    [Kozlov LV. Study of functional activity of components and factors of the human complement system. Voprosy meditsinskoi khimii. 2002;48(6):624–31. (In Russ)]

  25. Risitano A, Notaro R, Marando L, et al. Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood. 2009;113(17):4094–5100. doi: 10.1182/blood-2008-11-189944.

  26. Hill A, Rother R, Arnold L, et al. Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization. Haematologica. 2010;95(4):567–73. doi: 10.3324/haematol.2009.007229.

  27. Sugimori C, Chuhjo T, Feng H, et al. Minor population of CD55-CD59- blood cells predict response to immunosuppressive therapy and prognosis in patients with aplastic anaemia. Blood. 2006;107(4):1308–14. doi: 10.1182/blood-2005-06-2485.

  28. Sosie G, Mary J-Y, de Gramont A, et al. Paroxysmal noctural haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996;348(9027):573–7. doi: 10.1016/s0140-6736(95)12360-1.

  29. Araten D, Bessler M, McKenzie S, et al. Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): no evidence for intrinsic growth advantage of PNH clones. Leukemia. 2002;16(11):2243–8. doi: 10.1038/sj.leu.2402694.

  30. Cacciapuoti C, Terrazzano G, Barone L, et al. Glycosyl-phosphatidyl-inositol-defective granulocytes from paroxysmal nocturnal haemoglobinuria patients show increased bacterial ingestion but reduced respiratory burst induction. Am J Hematol. 2007;82(2):98–107. doi: 10.1002/ajh.20779.

  31. Вуд М.Э., Банн П.А. Секреты гематологии и онкологии. Пер. с англ. М.: Бином, 2001.

    [Wood M, Bunn P. Hematology/Oncology Secrets. ( ed.: Wood ME, Bunn PA. Sekrety gematologii i onkologii. Moscow: Binom Publ.; 2001.)]

  32. Brodsky R. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804–11. doi: 10.1182/blood-2014-02-522128.

Pure Red Cell Aplasia with M-Gradient: A Literature Review and Clinical Experience

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , ,

AV Pivnik1,2, AA Petrenko1, SV Kozhurin3, SA Mar’ina3

1 RUDN University, 6 Miklukho-Maklaya str., Moscow, Russian Federation, 117198

2 AS Loginov Moscow Clinical Scientific Center, 89 Entuziastov sh., Moscow, Russian Federation, 111123

3 National Medical Hematology Research Center, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Prof. Aleksandr Vasil’evich Pivnik, MD, PhD, 89 Entuziastov sh., Moscow, Russian Federation, 111123; Tel.: 8(495)304-30-39; e-mail: pivnikav@gmail.com

For citation: Pivnik AV, Petrenko AA, Kozhurin SV, Mar’ina SA. Pure Red Cell Aplasia with M-Gradient: A Literature Review and Clinical Experience. Clinical oncohematology. 2018;11(3):273–80.

DOI: 10.21320/2500-2139-2018-11-3-273-280

ABSTRACT

Background. Pure red cell aplasia (PRCA) is a rare syndrome characterized by a decrease of erythroid progenitor cell count in the bone marrow. M-gradient with both a light and a heavy chain types in PRCA patients is a rare phenomenon which is considered to be a specific form of the disease.

Aim. To review a clinical presentation, diagnostic capabilities, and treatment outcomes of PRCA with M-gradient.

Materials & Methods. The analysis included 10 patients. The most effective empirically established treatment program was 200–400 g of cyclophosphamide 2–3 times a week to a total dose of 6–10 g and loading courses of 100–120 mg of oral and 180–240 mg of intravenous prednisone daily within 5 days. On the 6th day prednisone injections were discontinued, and from the 7th day the oral dose of prednisone was gradually reduced to permanent discontinuation in 2–3 days. This treatment course was repeated 1–3 times at intervals of a week. Targeted enzyme immunoassay of M-gradient was performed in 4 patients in order to determine whether M-gradient is the sum of two antibody types, i.e. erythrokaryocyte antibodies and secondary anti-idiotype antibodies against primary antibodies.

Results. The total of 6 out of 10 PRCA patients reached complete remission within the period from 9 months to 22 years of follow-up, in 4 patients no remission was achieved. M-gradient contained IgG (n = 9) and IgA (n = 1) oligoclones. In typing it consisted of IgGλ (n = 4), IgGκ (n = 5) and IgAκ (n = 1). M-gradient enzyme immunoassay showed no primary and secondary anti-idiotype antibodies.

Conclusion. The obtained results allow to regard gammopathy in PRCA as an effect of oligoclonal hyper-immunoglobulin without any pathogenetic connection between M-gradient and PRCA.

Keywords: partial red cell aplasia of the bone marrow, PRCA, anemia, M-gradient, monoclonal gammopathy.

Received: February 5, 2018

Accepted: May 11, 2018

Read in PDF 

REFERENCES

  1. Japson JH, Lovenstein L. Panhypoplasia in the bone marrow. 1. Demonstration of a plasma factor with anti-erythropoietin-like activity. Can Med Assoc J. 1968;99(3):99–101.
  2. Гериатрическая гематология. Заболевания системы крови в старших возрастных группах. Под ред. Л.Д. Гриншпун, А.В. Пивника. М.: Медиум, 2012. Т. 2. С. 438–41.[Grinshpun LD, Pivnik AV, eds. Geriatricheskaya gematologiya. Zabolevaniya sistemy krovi v starshikh vozrastnykh gruppakh. (Geriatric hematology. Blood disorders in elderly patients.) Moscow: Medium Publ.; 2012, vol. 2. pp. 438–41. (In Russ)]
  3. Charles RJ, Sabo KM, Kidd PG, Abkowitz JL. The pathophysiology of pure red cell aplasia: implications for therapy. Blood. 1996;87(11):4831–8.
  4. Lacy MQ, Kurtin PJ, Tefferi A. Pure red cell aplasia: association with large granular lymphocyte leukemia and the prognostic value of cytogenetic abnormalities. Blood. 1996;87(7):3000–6.
  5. Руководство по гематологии. Под ред. А.И. Воробьева. 3-е изд. перераб. и доп. М.: Ньюдиамед, 2005. Т. 3. С. 274–85.[Vorob’ev AI, ed. Rukovodstvo po gematologii. (Guidelines on hematology.) 3rd revised edition. Moscow: Newdiamed Publ.; 2005, vol. 3. pp. 274–85. (In Russ)]
  6. Идельсон Л.И., Тер-Григоров B.C., Пивник A.B., Эткин А.Ф. Клинико-иммунологические особенности парциальной красноклеточной аплазии сочетанной с моноклональной гаммапатией. Терапевтический архив. 1983;8:75–9.[Idel’son LI, Ter-Grigorov VC, Pivnik AV, Etkin AF. Clinical and immunological profile of pure red cell aplasia together with monoclonal gammopathy. Terapevticheskii arkhiv. 1983;8:75–9. (In Russ)]
  7. Пивник А.В. Парциальная красноклеточная аплазия костного мозга: клиника, вопросы патогенеза, диагностика, лечение: Дис. … канд. мед. наук. М., 1978.[Pivnik AV. Partsial’naya krasnokletochnaya aplaziya kostnogo mozga: klinika, voprosy patogeneza, diagnostika, lechenie. (Pure red cell aplasia in bone marrow: clinical presentation, pathogenesis, diagnostics, treatment.) [dissertation] Moscow; 1978. (In Russ)]
  8. Андреева Н.Е., Чернохвостова Е.В. Иммуноглобулинопатии. М.: Медицина, 1985. 240 c.[Andreeva NE, Chernokhvostova EV. Immunoglobulinopatii. (Immunoglobulinopathy.) Moscow: Meditsina Publ.; 1985. 240 p. (In Russ)]
  9. Эткин А.Ф., Пивник А.В., Мамиляева З.Х. Олигоклональная парапротеинемия при парциальной аплазии костного мозга. Гематология и трансфузиология. 1987;4:31–4.[Etkin AF, Pivnik AV, Mamilyaeva ZKh. Oligoclonal paraproteinemia in partial red cell aplasia in the bone marrow. Gematologiya i transfuziologiya. 1987;4:31–4. (In Russ)]
  10. Kobayashi T, Hanada T, Sato Y, et al. A case of pure red cell aplasia with monoclonal gammopathy: immune-mediated inhibition of erythropoiesis. Rinsho Ketsueki. 1987;28(11):2029–33.
  11. Balducci L, Hardy C, Dreiling B, et al. Pure red blood cell aplasia associated with paraproteinemia: in vitro studies of erythropoiesis. Haematologia (Budap). 1984;17(3):353–7.
  12. Gu H, Lee WI, Jeon Y, et al. Pure Red Cell Aplasia Associated with Monoclonal Gammopathy of Undetermined Significance and Literature Review. Clin Lab. 2017;63(2):373–8. doi: 10.7754/Clin.Lab.2016.160730.
  13. Murate T, Ohashi H, Ichikawa A, et al. A case of pure red cell aplasia with monoclonal gammopathy. Nihon Naika Gakkai Zasshi. 1992;81(8):1263–5.
  14. Shimmyozu K, Tara M, Okadome T, et al. Pure red cell aplasia with monoclonal gammopathy and von Willebrand disease. Rinsho Ketsueki. 1990;31(9):1468–73.
  15. Korde N, Zhang Y, Loeliger K, et al. Monoclonal gammopathy-associated pure red cell aplasia. Br J Haematol. 2016;173(6):876–83. doi: 10.1111/bjh.14012.
  16. Идельсон Л.И., Койфман М.М., Горина Л.Г., Оловников А.М. Применение агрегат-гемагглютинационной пробы и других методов для диагностики аутоиммунной гемолитической анемии с отрицательной прямой пробой Кумбса. Проблемы гематологии. 1975;6:91–9.[Idel’son LI, Koifman MM, Gorina LG, Olovnikov AM. Application of an aggregate-hemagglutination test and other assays for the diagnosis of autoimmune hemolytic anaemia with a negative direct antiglobulin test. Problemy gematologii. 1975;6:91–9. (In Russ)]

Clinical Manifestation and Errors in the Diagnosis of Classical Paroxysmal Nocturnal Hemoglobinuria: A clinical case series of 150 patients

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , , ,

AD Kulagin, OU Klimova, AV Dobronravov, MO Ivanova, TA Rudakova, EV Babenko, VA Dobronravov, BV Afanas’ev

Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Aleksander Dmitrievich Kulagin, DSci, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Теl.: +7(812)338-62-36; e-mail: kulagingem@rambler.ru

For citation: Kulagin AD, Klimova OU, Dobronravov AV, et al. Clinical Manifestation and Errors in the Diagnosis of Classical Paroxysmal Nocturnal Hemoglobinuria: A clinical case series of 150 patient. Clinical oncohematology. 2017;10(3):333–41 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-333-341

ABSTRACT

Background. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease of the blood system, characterized by intravascular hemolysis, cytopenia and thrombosis. Diagnostic errors with delayed diagnosis of PNH are often due to the variety of the clinical presentation and the lack of awareness of the doctors of this rare disease.

Aim. The aim of the study was to characterize the options for clinical manifestation and the complexity of diagnosis of classical PNH.

Materials & Methods. The research included 150 patients with PNH. The inclusion criteria were: 1) clinical and laboratory signs of intravascular hemolysis; 2) verification of the diagnosis using standard flow cytometry; 3) absence of aplastic anemia, myelodysplastic syndrome and primary myelofibrosis. The patients were of 13 to 72 years old (median age 34 years). The study population consisted of 89 (59 %) women and 61 (41 %) men.

Results. The time before the diagnosis ranged from 0 to 455 months (median 33 months). The median size of the PNH clone among granulocytes and erythrocytes was 95 % and 41 %, respectively. The median of the lactic dehydrogenase was 7.2 times the upper limit of normal (ULN). Cytopenia occurred in 65 % of patients, including a combination of thrombocytopenia and neutropenia in 29 % of cases. Weakness and fatigue (99 %), hemoglobinuria (57 %), pain (52 %), icterus (46 %), dysphagia (37 %) and infection/fever (23 %) were the most common symptoms on the onset of the disease. Before the diagnosis of PNH, thrombosis or acute kidney injury was found in 22 % and 18 % of patients, respectively. Only 22 % of patients were initially diagnosed with PNH. In the remaining patients, the primary diagnosis was inadequate.

Conclusion. The clinical manifestation of PNH is characterised by the presence of hemoglobinuria, cytopenia and early thrombosis in 57 %, 65 % and 22 % of patients, respectively. Errors of the primary diagnosis reach 78 % and lead to inadequate treatment. The results of the research showed the need for multidisciplinary approach and strict adherence to diagnostic algorithms of PNH in the risk groups, according to current recommendations.

Keywords: paroxysmal nocturnal hemoglobinurea, PNH clone, cytopenia, clinical manifestation, diagnostic errors.

Received: February 20, 2017

Accepted: May 8, 2017

Read in PDF (RUS)pdficon

REFERENCES

  1. Takeda J, Miyata T, Kawagoe K, et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell. 1993;73(4):703–11. doi: 10.1016/0092-8674(93)90250-T.
  2. Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 2005;293(13):1653–62. doi: 10.1001/jama.293.13.1653.
  3. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699–709. doi: 10.1182/blood-2005-04-1717.
  4. Hillmen P, Lewis SM, Bessler M, et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333(19):1253–8. doi: 10.1056/NEJM199511093331904.
  5. Socie G, Mary JY, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet. 1996;348(9027):573–7. doi: 10.1016/S0140-6736(95)12360-1.
  6. Кулагин А.Д., Лисуков И.А., Птушкин В.В. и др. Национальные клинические рекомендации по диагностике и лечению пароксизмальной ночной гемоглобинурии. Онкогематология. 2014;9(2):20–8. doi: 10.17650/1818-8346-2014-9-2-20-28.
    [Kulagin AD, Lisukov IA, Ptushkin VV, et al. National clinical guidelines for the diagnosis and treatment of paroxysmal nocturnal hemoglobinuria. Oncohematology. 2014;9(2):20–8. doi: 10.17650/1818-8346-2014-9-2-20-28. (In Russ)]
  7. Dacie IV, Lewis SM. Paroxysmal nocturnal hemoglobinuria: clinical manifestation, haematology, and nature of the disease. Series Haematol. 1972;5(3):3–23.
  8. Nishimura J, Kanakura Y, Ware RE, et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine (Baltimore). 2004;83(3):193–207. doi: 10.1097/01.md.0000126763.68170.46.
  9. de Latour RP, Mary JY, Salanoubat C, et al. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood. 2008;112(8):3099–106. doi: 10.1182/blood-2008-01-133918.
  10. Ge M, Li X, Shi J, et al. Clinical features and prognostic factors of Asian patients with paroxysmal nocturnal hemoglobinuria: results from a single center in China. Ann Hematol. 2012;91(7):1121–8. doi: 10.1007/s00277-012-1413-6.
  11. Гаврилов О.К., Файнштейн Ф.Э., Турбина Н.С. Депрессии кроветворения. М.: Медицина, 1987. 256 c.
    [Gavrilov OK, Fainshtein FE, Turbina NS. Depressii krovetvorenia. (Hematopoiesis depressions.) Moscow: Meditsina Publ.; 1987. 256 p. (In Russ)]
  12. Moyo VM, Mukhina GL, Garrett ES, Brodsky RA. Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. Br J Haematol. 2004;126(1):133–8. doi: 10.1111/j.1365-2141.2004.04992.x.
  13. Schrezenmeier H, Muus P, Socie G, et al. Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry. Haematologica. 2014;99(5):922–9. doi: 10.3324/haematol.2013.093161.
  14. Kulagin A, Lisukov I, Ivanova M, et al. Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two-centre prospective study. Br J Haematol. 2014;164(4):546–54. doi: 10.1111/bjh.12661.
  15. Kulagin A, Golubovskaya I, Ivanova M, et al. Incidence and risk factors for hemolytic paroxysmal nocturnal hemoglobinuria (PNH) in aplastic anemia (AA) patients. Bone Marrow Transplant. 2014;49(Suppl 1):S42–3. doi: 10.1038/bmt.2014.43.
  16. Sipol AA, Babenko EV, Borisov VI, et al. An inter-laboratory comparison of PNH clone detection by high-sensitivity flow cytometry in a Russian cohort. Hematology. 2015;20(1):31–8. doi: 10.1179/1607845414Y.0000000162.
  17. Kim JS, Jang JH, Yoon SS, et al. Distinct subgroups of paroxysmal nocturnal hemoglobinuria (PNH) with cytopenia: results from South Korean National PNH Registry. Ann Hematol. 2016;95(1):125–33. doi: 10.1007/s00277-015-2511-z.
  18. Yu F, Du Y, Han B. A comparative analysis of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria between Asia and Europe/America. Int J Hematol. 2016;103(6):649–54. doi: 10.1007/s12185-016-1995-1.
  19. Kulagin A, Klimova O, Dobronravov A, et al. Incidence, clinical characteristics and outcome of symptomatic thromboembolic events (TE) in 276 patients with paroxysmal nocturnal hemoglobinurea (PNH). Blood (ASH Annual Meeting Abstracts). 2016;128(22):5072.
  20. Richani K, Soto E, Romero R, et al. Normal pregnancy is characterized by systemic activation of the complement system. J Mat Fet Neonat Med. 2005;17(4):239–45. doi: 10.1080/14767050500072722.
  21. de Guibert S, de Latour RP, Varoqueaux N, et al. Paroxysmal nocturnal hemoglobinuria and pregnancy before the eculizumab era: the French experience. Haematologica. 2011;96(9):1276–83. doi: 10.3324/haematol.2010.037531.
  22. Nakao S. Diagnostic problems in acquired bone marrow failure syndromes. Int J Hematol. 2016;104(2):151–2. doi: 10.1007/s12185-016-2057-4.

Secondary Hemophagocytic Syndrome in the Adult Patients. Literature Review and Authors’ Experience

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , , ,

VG Potapenko1,2, NA Potikhonova4, VV Baikov2, MB Belogurova1, IA Lisukov3, AV Klimovich1, SV Lapin2, MO Ivanova2, VM Kravtsova2, EI Podol’tseva1, NV Medvedeva1, BV Afanas’ev2

1 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

2 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

3 I.I. Mechnikov North-Western State Medical University, 41 Kirochnaya str., Saint Petersburg, Russian Federation, 197022

4 Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Vsevolod Gennad’evich Potapenko, Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110; Tel.: +7(812)230-19-33; e-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko V.G., Potikhonova N.A., Baikov V.V., Belogurova M.B., Lisukov I.A., Klimovich A.V., Lapin S.V., Ivanova M.O., Kravtsova V.M., Podol’tseva E.I., Medvedeva N.V., Afanas’ev B.V. Secondary Hemophagocytic Syndrome in the Adult Patients. Literature Review and Authors’ Experience. Klin. Onkogematol. 2015;8(2):169–84. (In Russ.).

ABSTRACT

Background & Aims. The hemophagocytic syndrome is a dangerous hyperinflammatory syndrome usually caused by an infection. It is a result of excessive cell activation in the mononuclear phagocyte system which is manifested itself through cytopenia, systemic inflammatory reaction, liver and spleen impairment. Since the disease is rare and its diagnosing is very complicated, this syndrome has not been studied thoroughly and is overlooked very often. The aim of this work is to describe authors’ experience in dealing with the secondary hemophagocytic syndrome (HPS) and to present a literature review.

Methods. Clinical and laboratory data of 15 patients aged 16 to 64 (median age 48 years) with secondary HPS observed over the period from 2009 till 2013 were analyzed. Secondary HPS was diagnosed in patients with malignant lymphoproliferative and infectious diseases. HPS signs were found in lymphoproliferative disorders (n = 5), chronic active EBV-infection (n = 3), allogeneic hematopoietic stem cell transplantation (n = 3), acute leukemia (n = 1), multiple myeloma (n = 1), pneumonia (n = 1), and glomerulonephritis (n = 1). 8 patients underwent treatment for HPS: etoposide (n = 1), glucocorticoids (n = 1), intravenous immunoglobulin (n = 2), combination of rituximab + glucocorticoids (n = 2), etoposide + cyclosporine A (n = 1), as well as combined HLH-2004 chemotherapy (n = 1). The median observation period was 42 months.

Results. Among 15 adult patients enrolled into the retrospective analysis, malignant lymphoproliferative disorders and chronic EBV-infection were most common underlying disorders in case of secondary HPS. Early diagnosing is very complicated, because diagnostic criteria accepted at present are typical for the late-phase HPS. The above factors require development of more sensitive and universal diagnostic criteria.

Conclusion. In oncohematological practice, the secondary HPS is a severe complication requiring differential diagnosing with other critical conditions and intensive care. In case of HPS associated with oncohematological disorders, patients require close monitoring throughout the antitumor treatment period and after it.

Keywords: secondary hemophagocytic syndrome, lymphoma, Epstein-Barr virus, etoposide, hematopoietic stem cells transplantation.

Received: December 9, 2014

Accepted: February 7, 2015

Read in PDF (RUS)pdficon

REFERENCES

  1. Carroll WL, Finlay JL, Sudbury MA. Cancer in children and adolescents. Jones & Bartlett; 2010. pp. 254–6.
  2. Chu T, D’Angio GJ, Favara B, et al. Histiocytosis syndromes in children. The Lancet. 1987;329(8526):208–9. doi: 10.1016/s0140-6736(87)90016-x.
  3. Favara BE, Feller AC, Pauli M, et al. Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol. 1997;29(3):157–66. doi: 10.1002/(sici)1096-911x(199709)29:3<157::aid-mpo1>3.0.co;2-c.
  4. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008.
  5. Jordan MB, Allen CE, Weitzman S, et al. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041–52. doi: 10.1182/blood-2011-03-278127.
  6. Janka GE. Hemophagocytic syndromes. Blood Rev. 2007;21(5):245–53. doi: 10.1016/j.blre.2007.05.001.
  7. Gotze KS, Hoffmann D, Schatzl HM, et al. Fatal Epstein-Barr virus-associated lymphoproliferative disorder following treatment with a novel mTOR inhibitor for relapsed chronic lymphocytic leukemia leukemia cells. Haematologica. 2007;92(9):1282–3. doi: 10.3324/haematol.11155.
  8. Emmenegger U, Schaer DJ, Larroche C, et al. Haemophagocytic syndromes in adults: current concepts and challenges ahead. Swiss Med Wkly. 2005;135(21-22):299–314.
  9. Arico M, Danesino C, Pende D, Moretta L. Pathogenesis of hemophagocytic lymphohistiocytosis. Br J Haematol. 2001;114(4):761–9. doi: 10.1046/j.1365-2141.2001.02936.x.
  10. Henter JI, Horne A, Arico M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–31. doi: 10.1002/pbc.21039.
  11. Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology. 2009;2009(1):127–31. doi: 10.1182/asheducation-2009.1.127.
  12. Trottestam H, Horne A, Arico M, et al. Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood. 2011;118(17):4577–84. doi: 10.1182/blood-2011-06-356261.
  13. Охотникова Е.Н., Меллина К.В., Усова Е.И. и др. Гемофагоцитарный синдром в педиатрической практике. Клиническая иммунология, аллергология, инфектология. 2008;2(13):61–70.
    [Okhotnikova EN, Mellina KV, Usova EI, et al. Hematophagocytic syndrome in pediatric practice. Klinicheskaya immunologiya, allergologiya, infektologiya. 2008;2(13):61–70. (In Russ)]
  14. Diaz-Guzman E, Dong B, Hobbs SB, et al. Hemophagocytic lymphohistiocytosis after lung transplant: report of 2 cases and a literature review. Exp Clin Transplant. 2011;9(3):217–22.
  15. Охотникова Е.Н., Меллина К.В., Усова Е.И. и др. Гемофагоцитарный синдром в педиатрической практике (Обзор литературы). Здоровье ребенка. 2008;4(13):131–8.
    [Okhotnikova EN, Mellina KV, Usova EI, et al. Hematophagocytic syndrome in pediatric practice (literature review). Zdorov’e rebenka. 2008;4(13):131–8. (In Russ)]
  16. Karapinar B, Yilmaz D, Balkan C, et al. An unusual cause of multiple organ dysfunction syndrome in the pediatric intensive care unit: hemophagocytic lymphohistiocytosis. Pediatr Crit Care Med. 2009;10(3):285–90. doi: 10.1097/pcc.0b013e318198868b.
  17. Schaer DJ, Schaer CA, Schoedon G, et al. Hemophagocytic macrophages constitute a major compartment of heme oxygenase expression in sepsis. Eur J Haematol. 2006;77(5):432–6. doi: 10.1111/j.1600-0609.2006.00730.x.
  18. Besset S, Schnell D, Azoulay E. Hemophagocytic lymphohistiocytosis mimicking septic shock. Chest. 2012;141(3):835; author reply 836. doi: 10.1378/chest.11-2717.
  19. Raschke RA, Garcia-Orr R. Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults. Chest. 2011;140(4):933–8. doi: 10.1378/chest.11-0619.
  20. Gupta A, Tyrrell P, Valani R, et al. The role of the initial bone marrow aspirate in the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008;51(3):402–4. doi: 10.1002/pbc.21564.
  21. Wang Z, Chen X, Wu L, et al. Significance of hemophagocytosis in diagnosis of hemophagocytic lymphohistiocytosis. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009;17(4):1064–6.
  22. Favara BE. Histopathology of the liver in histiocytosis syndromes. Pediatr Pathol Lab Med. 1996;16(3):413–33. doi: 10.3109/15513819609168681.
  23. Wang Z, Wang YN, Feng CC, et al. Diagnostic significance of NK cell activity and soluble CD25 level in serum from patients with secondary hemophagocytic lymphohistiocytosis. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008;16(5):1154–7.
  24. Wang LL, Hu YX, Chen WF, et al. Significance of soluble interleukin-2 receptor and NK cell activity in patients with hemophagocytic lymphohistiocytosis. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012;20(2):401–4.
  25. Wang Z, Wang YN, Feng CC, et al. The early diagnosis and clinical analysis of 57 cases of acquired hemophagocytic lymphohistiocytosis. Zhonghua Nei Ke Za Zhi. 2009;48(4):312–5.
  26. Gotoh Y, Okamoto Y, Uemura O, et al. Determination of age-related changes in human soluble interleukin 2 receptor in body fluids of normal subjects as a control value against disease states. Clin Chim Acta. 1999;289(1–2):89–97. doi: 10.1016/s0009-8981(99)00161-8.
  27. Rothkrantz-Kos S, Drent M, Schmitz MP, et al. Biochemical parameters in monitoring severity of sarcoidosis. Chapter 4: Analytical evaluation and determination of reference values of soluble interleukin-2-receptor and serum amyloid-A. 2004.
  28. Janka G. Hemophagocytic lymphohistiocytosis: when the immune system runs amok. Klin Padiatr. 2009;221(5):278–85. doi: 10.1055/s-0029-1237386.
  29. Crook MA. Hyperferritinaemia; laboratory implications. Ann Clin Biochem. 2012;49(Pt 3):211–3. doi: 10.1258/acb.2012.012059.
  30. Park HS, Kim DY, Lee JH, et al. Clinical features of adult patients with secondary hemophagocytic lymphohistiocytosis from causes other than lymphoma: an analysis of treatment outcome and prognostic factors. Ann Hematol. 2012;91(6):897–904. doi: 10.1007/s00277-011-1380-3.
  31. Dhote R, Simon J, Papo T, et al. Reactive hemophagocytic syndrome in adult systemic disease: report of twenty-six cases and literature review. Arthritis Rheum. 2003;49(5):633–9. doi: 10.1002/art.11368.
  32. Mayordomo-Colunga J, Rey C, Gonzalez S, Concha A. Multiorgan failure due to hemophagocytic syndrome: A case report. Cases J. 2008;1(1):209. doi: 10.1186/1757-1626-1-209.
  33. Karras A, Thervet E, Legendre C. Hemophagocytic syndrome in renal transplant recipients: report of 17 cases and review of literature. Transplantation. 2004;77(2):238–43. doi: 10.1097/01.tp.0000107285.86939.37.
  34. Han AR, Lee HR, Park BB, et al. Lymphoma-associated hemophagocytic syndrome: clinical features and treatment outcome. Ann Hematol. 2007;86(7):493–8. doi: 10.1007/s00277-007-0278-6.
  35. Wijsman CA, Roeters van Lennep JE, von dem Borne PA, Fogteloo AJ. A diagnostic difficulty: two cases of haemophagocytic syndrome in adults. Neth J Med. 2009;67(1):29–31.
  36. Machaczka M. Hemophagocytic lymphohistiocytosis–a contemporary medical problem. Pol Merkur Lekarski. 2012;32(187):59–63.
  37. Allen CE, Yu X, Kozinetz CA, McClain KL. Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008;50(6):1227–35. doi: 10.1002/pbc.21423.
  38. Henter JI, Samuelsson-Horne A, Arico M, et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002;100(7):2367–73. doi: 10.1182/blood-2002-01-0172.
  39. Shin HJ, Chung JS, Lee JJ, et al. Treatment Outcomes with CHOP Chemotherapy in Adult Patients with Hemophagocytic Lymphohistiocytosis. J Korean Med Sci. 2008;23(3):439–44. doi: 10.3346/jkms.2008.23.3.439.
  40. Goede JS, Peghini PE, Fehr J. Oral Low Dose Etoposide in the Treatment of Macrophage Activation Syndrome. Blood (ASH Annual Meeting Abstracts). 2004;104:3817.
  41. Bhattacharyya M, Ghosh MK. Hemophagoctic lymphohistiocytosis–recent concept. J Assoc Physicians India. 2008;56:453–7.
  42. Imashuku S, Hibi S, Kuriyama K, et al. Management of severe neutropenia with cyclosporin during initial treatment of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis. Leuk Lymphoma. 2000;36(3–4):339–46. doi: 10.3109/10428190009148855.
  43. Ishii E, Ohga S, Imashuku S, et al. Review of hemophagocytic lymphohistiocytosis (HLH) in children with focus on Japanese experiences. Crit Rev Oncol Hematol. 2005;53(3):209–23. doi: 10.1016/j.critrevonc.2004.11.002.
  44. Emmenegger U, Reimers A, Frey U, et al. Reactive macrophage activation syndrome: a simple screening strategy and its potential in early treatment initiation. Swiss Med Wkly. 2002;132(17–18):230–6.
  45. Imashuku S, Kuriyama K, Teramura T, et al. Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Clin Oncol. 2001;19(10):2665–73.
  46. Imashuku S, Kuriyama K, Sakai R, et al. Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: A report from the HLH study center. Med Pediatr Oncol. 2003;41(2):103–9. doi: 10.1002/mpo.10314.
  47. Bosman G, Langemeijer SM, Hebeda KM, et al. The role of rituximab in a case of EBV–related lymphoproliferative disease presenting with haemophagocytosis. Neth J Med. 2009;67(8):364–5.
  48. Kimura H. Pathogenesis of chronic active Epstein-Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency? Rev Med Virol. 2006;16(4):251–61. doi: 10.1002/rmv.505.
  49. Imashuku S, Teramura T, Tauchi H, et al. Longitudinal follow-up of patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Haematologica. 2004;89(2):183–8.
  50. Balamuth NJ, Nichols KE, Paessler M, Teachey DT. Use of rituximab in conjunction with immunosuppressive chemotherapy as a novel therapy for Epstein Barr virus-associated hemophagocytic lymphohistiocytosis. J Pediatr Hematol Oncol. 2007;29(8):569–73. doi: 10.1097/mph.0b013e3180f61be3.
  51. Bosman G, Langemeijer SM, Hebeda KM, et al. The role of rituximab in a case of EBV-related lymphoproliferative disease presenting with haemophagocytosis. Neth J Med. 2009;67(8):364–5.
  52. So MW, Koo BS, Kim YJ, et al. Successful rituximab treatment of refractory hemophagocytic lymphohistiocytosis and autoimmune hemolytic anemia associated with systemic lupus erythematosus. Mod Rheumatol. 2013 Feb 7 (abstract). doi: 10.1007/s10165-013-0838-7.
  53. Stebbing J, Ngan S, Ibrahim H, et al. The successful treatment of haemophagocytic syndrome in patients with humanimmunodeficiency virus-associated multi-centric Castleman’s disease. Clin Exp Immunol. 2008;154(3):399–405. doi: 10.1111/j.1365-2249.2008.03786.x.
  54. Масчан М. Молекулярно-генетическая диагностика и дифференциальная терапия гистиоцитарных пролиферативных заболеваний у детей: Автореф. ¼ д-ра мед. наук. М., 2011.
    [Maschan M. Molekulyarno-geneticheskaya diagnostika i differentsial’naya terapiya gistiotsitarnykh proliferativnykh zabolevanii u detei. (Molecular genetic diagnosis and differentiated therapy of histiocytic proliferative diseases in children.) [dissertation] Moscow; 2011. (In Russ)]
  55. Filipovich A, McClain K, Grom A. Histiocytic disorders: recent insights into pathophysiology and practical guidelines. Biol Blood Marrow Transplant. 2010;16(1 Suppl):S82–9. doi: 10.1016/j.bbmt.2009.11.014.
  56. Shabbir M, Lucas J, Lazarchick J, Shirai K. Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a single institution and a review of literature. Hematol Oncol. 2011;29(2):100–6. doi: 10.1002/hon.960.
  57. Ramanan AV, Schneider R. Macrophage activation syndrome–what’s in a name! Rheumatol. 2003;30(12):2513–6.
  58. Weitzman S. Approach to hemophagocytic syndromes. Hematology Am Soc Hematol Educ Program. 2011;2011(1):178–83.
  59. Sada E, Shiratsuchi M, Kiyasu J, et al. Primary mediastinal non-seminomatous germ cell tumor associated with hemophagocytic syndrome. J Clin Exp Hematol. 2009;49(2):117–20. doi: 10.3960/jslrt.49.117.
  60. Chaudary IU, Bojal SA, Attia A, et al. Mediastinal endodermal sinus tumor associated with fatal hemophagocytic syndrome. Hematol Oncol Stem Cell Ther. 2011;4(3):138–41. doi: 10.5144/1658-3876.2011.138.
  61. Kounami S, Nakayama K, Yoshiyama M, et al. Early-onset hemophagocytic lymphohistiocytosis after the start of chemotherapy for advanced neuroblastoma. Pediatr Hematol Oncol. 2012;29(1):99–103. doi: 10.3109/08880018.2011.643529.
  62. Karapinar B, Yilmaz D, Balkan C, et al. An unusual cause of multiple organ dysfunction syndrome in the pediatric intensive care unit: hemophagocytic lymphohistiocytosis. Pediatr Crit Care Med. 2009;10(3):285–90. doi: 10.1097/pcc.0b013e318198868b.
  63. Takahashi N. Lymphoma-associated hemophagocytic syndrome (LAHS). Nihon Rinsho. 2000;58(3):665–8 (abstract).
  64. Chang CS, Wang CH, Su IJ, et al. Hematophagic histiocytosis: a clinicopathologic analysis of 23 cases with special reference to the association with peripheral T-cell lymphoma. J Formos Med Assoc. 1994;93:421–8.
  65. Miyahara M, Sano M, Shibata K, et al. B-cell lymphoma-associated hemophagocytic syndrome: clinicopathological characteristics. Ann Hematol. 2000;79(7):378–88. doi: 10.1007/s002770000155.
  66. Takahashi N, Miura I, Chubachi A, et al. A clinicopathological study of 20 patients with T/natural killer (NK)-cell lymphoma-associated hemophagocytic syndrome with special reference to nasal and nasal-type NK/T-cell lymphoma. Int J Hematol. 2001;74(3):303–8. doi: 10.1007/bf02982065.
  67. Abe Y, Hara K, Shiratsuchi M, et al. Two cases of B cell lymphoma associated with hemophagocytic syndrome. Rinsho Ketsueki. 2001;42(1):35–40.
  68. Shimazaki C, Inaba T, Okano A, et al. Clinical characteristics of B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS): comparison of CD5+ with CD5- B-LAHS. Intern Med. 2001;40(9):878–82. doi: 10.2169/internalmedicine.40.878.
  69. Janka G, Imashuku S, Elinder G, et al. Infection- and malignancy-associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am. 1998;12(2):435–44. doi: 10.1016/s0889-8588(05)70521-9.
  70. Matzner Y, Behar A, Beeri E, et al. Systemic leishmaniasis mimicking malignant histiocytosis. Cancer. 1979;43(1):398–402. doi: 10.1002/1097-0142(197901)43:1<398::aid-cncr2820430156>3.0.co;2-3.
  71. Castillo L, Carcillo J. Secondary hemophagocytic lymphohistiocytosis and severe sepsis/systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med. 2009;10(3):387–92. doi: 10.1097/pcc.0b013e3181a1ae08.
  72. Karapinar B, Yilmaz D, Balkan C, et al. An unusual cause of multiple organ dysfunction syndrome in the pediatric intensive care unit: hemophagocytic lymphohistiocytosis. Pediatr Crit Care Med. 2009;10(3):285–90. doi: 10.1097/pcc.0b013e318198868b.
  73. Buyse S, Teixeira L, Galicier L, et al. Critical care management of patients with hemophagocytic lymphohistiocytosis. Intens Care Med. 2010;36(10):1695–702. doi: 10.1007/s00134-010-1936-z.
  74. Takahashi N, Chubachi A, Kume M, et al. A clinical analysis of 52 adult patients with hemophagocytic syndrome: the prognostic significance of the underlying diseases. Int J Hematol. 2001;74(2):209–13. doi: 10.1007/bf02982007.
  75. Cohen JI, Jaffe ES, Dale JK, et al. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood. 2011;117(22):5835–49. doi: 10.1182/blood-2010-11-316745.
  76. Ishii E, Ohga S, Imashuku S, et al. Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. Int J Hematol. 2007;86(1):58–65. doi: 10.1532/ijh97.07012.
  77. Xiao L, Xian Y, Dai BT, et al. Clinical features and outcome analysis of 83 childhood Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with HLH-2004 protocol. Zhonghua Xue Ye Xue Za Zhi. 2011;32(10):668–72.
  78. Maia DM, Peace-Brewer AL. Chronic, active Epstein-Barr virus infection. Curr Opin Hematol. 2000;7(1):59–63. doi: 10.1097/00062752-200001000-00011.
  79. Kunitomi A, Kimura H, Ito Y, et al. Unrelated bone marrow transplantation induced long-term remission in a patient with life-threatening Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Clin Exp Hematol. 2011;51(1):57–61. doi: 10.3960/jslrt.51.57.
  80. Ohshima K, Suzumiya J, Sugihara M, et al. Clinicopathological study of severe chronic active Epstein-Barr virus infection that developed in association with lymphoproliferative disorder and/or hemophagocytic syndrome. Pathol Int. 1998;48(12):934–43. doi: 10.1111/j.1440-1827.1998.tb03864.x.
  81. Katano H, Ali MA, Patera AC, et al. Chronic active Epstein-Barr virus infection associated with mutations in perforin that impair its maturation. Blood. 2004;103(4):1244–52. doi: 10.1182/blood-2003-06-2171.
  82. Kasahara Y, Yachie A, Takei K, et al. Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection. Blood. 2001;98(6):1882–8. doi: 10.1182/blood.v98.6.1882.
  83. Taniai N, Akimaru K, Kawano Y, et al. Hemophagocytic syndrome after living-donor liver transplantation for fulminant liver failure: a case report. Hepatogastroenterology. 2005;52(63):923–6.
  84. Yoshizumi T, Taketomi A, Kayashima H, et al. Successful treatment for a patient with hemophagocytic syndrome after a small-for-size graft liver transplantation. Hepatogastroenterology. 2008;55(82–83):359–62.
  85. Soyama A, Eguchi S, Takatsuki M, et al. Hemophagocytic syndrome after liver transplantation: report of two cases. Surg Today. 2011;41(11):1524–30. doi: 10.1007/s00595-010-4512-9.
  86. Fukunaga A, Nakamura F, Yoshinaga N, et al. Successful treatment with combined chemotherapy of two adult cases of hemophagocytic lymphohistiocytosis in recipients of umbilical cord blood cell transplantation. Int J Hematol. 2011;93(4):551–4. doi: 10.1007/s12185-011-0792-0.
  87. Asano T, Kogawa K, Morimoto A, et al. Hemophagocytic lymphohistiocytosis after hematopoietic stem cell transplantation in children: a nationwide survey in Japan. Pediatr Blood Cancer. 2012;59(1):110–4. doi: 10.1002/pbc.23384.
  88. Abdelkefi A, Ben Jamil W, Torjman L, et al. Hemophagocytic syndrome after hematopoietic stem cell transplantation: a prospective observational study. Int J Hematol. 2009;89(3):368–73. doi: 10.1007/s12185-009-0261-1.
  89. Okano M, Kawa K, Kimura H, et al. Proposed Guidelines for Diagnosing Chronic Active Epstein-Barr Virus Infection. Am J Hematol. 2005;80(1):64–9. doi: 10.1002/ajh.20398.
  90. Horne A, Trottestam H, Arico M, et al. Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis. Br J Haematol. 2008;140(3):327–35. doi: 10.1111/j.1365-2141.2007.06922.x.
  91. Gupta S, Weitzman S. Primary and secondary hemophagocytic lymphohistiocytosis: clinical features, pathogenesis and therapy. Exp Rev Clin Immunol. 2010;6(1):137–54. doi: 10.1586/eci.09.58.

Modern Approaches to Diagnosis and Treatment of Essential Thrombocythemia: Literature Review and Own Experience

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , ,

KM Abdulkadyrov, VA Shuvaev, IS Martynkevich

Russian Scientific Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Vasilii Anatol’evich Shuvaev, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel. +7 (921) 636-54-72; e-mail: shuvaev77@mail.ru

For citation: Abdulkadyrov KM, Shuvaev VA, Martynkevich IS. Modern Approaches to Diagnosis and Treatment of Essential Thrombocythemia: Literature Review and Own Experience. Clinical oncohematology. 2015;8(3):235–47 (In Russ).

ABSTRACT

Objective. The aim of our study was to present literature data and own experience about epidemiology, terminology, etiology and pathogenesis of еssential thrombocythemia.

Methods. Molecular and genetic aspects of the disease pathogenesis and its clinical manifestations are described. The article dwells on issues related to diagnostic criteria, differential diagnosis and classification of essential thrombocythemia. Results of molecular genetic and cytogenetic studies, major causes of thrombotic complications, and methods of their prevention and treatment are presented. Treatment options and monitoring, as well as evaluation of the treatment effectiveness get considerable coverage. Literature review and analysis of diagnostic and treatment results of 218 essential thrombocythemia patients are presented: of them 161 were females, 57 were males, the gender ratio was 2.8:1, and the median age was 57.2 (varied from 18.3 to 89.3 years). Chromosomal aberrations were found in 7 (9.3 %) of 65 patients who had undergone cytogenetic testing. A JAK2V617F mutation was identified in 79 (58.1 %) of 136 patients, and a MPL gene mutation in 1 (2.3 %) of 44 patients.

Results. The overall 10 year survival rate of 218 essential thrombocythemia patients was 83.9 %. Progression in the form of secondary post-essential thrombocythemia myelofibrosis was registered in 13 (6 %) patients. The treatment included hydroxyurea (n = 132), interferons-a (n = 37), anagrelide (n = 10), and acetylsalicylic acid (n = 54). The mortality rate over the whole 10 year observation period was 16.1 % (n = 35).

Conclusion. Timely and early diagnosis of essential thrombocythemia, thrombosis risk-adapted management and adequate follow-up with platelet count monitoring are cornerstones for preservation of patient’s duration and quality of life.

Keywords: essential thrombocythemia, Janus kinase 2 (JAK2) gene mutation, thrombotic complications risk, diagnostic and treatment algorithm.

Received: January 14, 2015

Accepted: May 26, 2015

Read in PDF (RUS)pdficon

REFERENCES

  1. Izaguirre-Avila R, Penia-Diaz A, De la Barinagarrementeria-Aldatz F, et al. Effect of Clopidogrel on Platelet Aggregation and Plasma Concentration of Fibrinogen in Subjects with Cerebral or Coronary Atherosclerotic Disease. Clin Applied Thromb Hemost. 2002;8(2):169–77. doi: 10.1177/107602960200800214.
  2. Абдулкадыров К.М. Клиническая гематология: справочник. СПб.: Питер Принт, 2006. 447 с.
    [Abdulkadyrov KM. Klinicheskaya gematologiya: spravochnik. (Clinical hematology: textbook.) Saint Petersburg: Piter Print Publ.; 2006. 447 p. (In Russ)]
  3. Воробьев А.И. Руководство по гематологии. М.: Ньюдиамед, 2003. Ч. 3. С. 9–15.
    [Vorob’ev AI. Rukovodstvo po gematoligii. (Guidelines in Hematology.) Moscow: NewDiamed Publ.; 2003. Vol. 3. pp. 9–15. (In Russ)]
  4. Абдулкадыров К.М., Шуваев В.А. Эссенциальная тромбоцитемия: современные представления о диагностике и лечении. СПб., 2014. 49 с.
    [Abdulkadyrov KM, Shuvaev VA. Essentialnaya trombocytemia: sovremennye predstavleniya o diagnostike i lechenii. (Essential thrombocythemia: modern concepts about diagnostics and treatment.) Saint Petersburg; 2014. 49 p. (In Russ)]
  5. Epstein E, Goedel A. Hammorhagische thrombocythamie bei vascularer schrumpfmilz. Virchow Arch. (Pathol. Anat.) 1934;292(2):233–48. doi: 10.1007/bf01891529.
  6. Dameshek W. Editorial: Some Speculations on the Myeloproliferative Syndromes. Blood. 1951;6(4):372–5.
  7. Mesa RA, Silverstein MN, Jacobsen SJ, et al. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: An Olmsted county study, 1976–1995. Am J Hematol. 1999;61(1):10–5. doi: 10.1002/(sici)1096-8652(199905)61:1<10::aid-ajh3>3.0.co;2-i.
  8. Tefferi A, Solberg LA Jr, Silverstein MN. A clinical update in polycythemia vera and essential thrombocythemia. Am J Med. 2000;109(2):141–9. doi: 10.1016/s0002-9343(00)00449-6.
  9. Shuvaev VA, Abdulkadyrova AS, Martynkevich IS, et al. Essential thrombocythemia – population analysis, a single center 10-years’ experience. ELN Inform Letter. October 2013:21.
  10. Beer PA, Erber WN, Campbell PJ, et al. How I treat essential thrombocythemia. Blood. 2011;117(5):1472–82. doi: 10.1182/blood-2010-08-270033.
  11. Levine RL, Heaney M. New advances in the pathogenesis and therapy of essential thrombocythemia. Hematology Am Soc Hematol Educ Program. 2008(1):76–82. 10.1182/asheducation-2008.1.76.
  12. Vannucchi AM, Guglielmelli P. Molecular pathophysiology of Philadelphia-negative myeloproliferative disorders: beyond JAK2 and MPL mutations. Haematologica. 2008;93(7):972–6. doi: 10.3324/haematol.13266.
  13. Tefferi A. Polycythemia vera and essential thrombocythemia: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013;88(6):507–16. doi: 10.1002/ajh.23417.
  14. Barosi G, Mesa R, Finazzi G, et al. Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project. Blood. 2013;121(23):4778–81. doi: 10.1182/blood-2013-01-478891.
  15. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms. N Engl J Med. 2013;369(25):2379–90. doi: 10.1056/nejmoa1311347.
  16. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405. doi: 10.1056/nejmoa1312542.
  17. Hofmann SR, Lam AQ, Frank S, et al. Jak3-Independent Trafficking of the Common g Chain Receptor Subunit: Chaperone Function of Jaks Revisited. Mol Cell Biol. 2004;24(11):5039–49. doi: 10.1128/mcb.24.11.5039-5049.2004.
  18. Kamakura S, Oishi K, Yoshimatsu T, et al. Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling. Nat Cell Biol. 2004;6(6):547–54. doi: 10.1038/ncb1138.
  19. Campbell PJ, Scott LM, Buck G, et al. Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. The Lancet. 2005;366(9501):1945–53. doi: 10.1016/s0140-6736(05)67785-9.
  20. Levine RL, Heaney M. New Advances in the Pathogenesis and Therapy of Essential Thrombocythemia. ASH Educ Program Book. 2008:76–82. doi: 10.1182/asheducation-2008.1.76.
  21. Tefferi A, Thiele J, Vannucchi AM, Barbui T. An overview on CALR and CSF3R mutations and a proposal for revision of WHO diagnostic criteria for myeloproliferative neoplasms. Leukemia. 2014;28(7):1407–13. doi: 10.1038/leu.2014.35.
  22. Abe M, Suzuki K, Inagaki O, et al. A novel MPL point mutation resulting in thrombopoietin-independent activation. Leukemia. 2002;16(8):1500–6. doi: 10.1038/sj.leu.2402554.
  23. Rotunno G, Mannarelli C, Guglielmelli P, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood. 2013;123(10):1552–5. doi: 10.1182/blood-2013-11-538983.
  24. Rumi E, Pietra D, Ferretti V, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2013;123(10):1544–51. doi: 10.1182/blood-2013-11-539098.
  25. Kiladjian J-J, Rain J-D, Bernard J-F, et al. Long-Term Incidence of Hematological Evolution in Three French Prospective Studies of Hydroxyurea and Pipobroman in Polycythemia Vera and Essential Thrombocythemia. Semin Thromb Hemost. 2006;32(4):417–21. doi: 10.1055/s-2006-942762.
  26. Nielsen I, Hasselbalch HC. Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan. Am J Hematol. 2003;74(1):26–31. doi: 10.1002/ajh.10375.
  27. Passamonti F, Rumi E, Arcaini L, et al. Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients. Haematologica. 2008;93(11):1645–51. doi: 10.3324/haematol.13346.
  28. Passamonti F, Rumi E, Pungolino E, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med. 2004;117(10):755–61. doi: 10.1016/j.amjmed.2004.06.032.
  29. Alvarez-Larran A, Cervantes F, Bellosillo B, et al. Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients. Leukemia. 2007;21(6):1218–23. doi: 10.1038/sj.leu.2404967.
  30. Campbell PJ, MacLean C, Beer PA, et al. Correlation of blood counts with vascular complications in essential thrombocythemia: analysis of the prospective PT1 cohort. Blood. 2012;120(7):1409–11. doi: 10.1182/blood-2012-04-424911.
  31. Ruggeri M, Tosetto A, Frezzato M, et al. The Rate of Progression to Polycythemia Vera or Essential Thrombocythemia in Patients with Erythrocytosis or Thrombocytosis. Ann Intern Med. 2003;139(6):470–5. doi: 10.7326/0003-4819-139-6-200309160-00009.
  32. Murphy S, Peterson P, Iland H, Laszlo J. Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. Semin Hematol. 1997;34(1):29–39.
  33. Panani AD. Cytogenetic Findings in Untreated Patients with Essential Thrombocythemia. In Vivo. 2006;20(3):381–4.
  34. Thiele J, Kvasnicka HM, Facchetti F, et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90(8):1128–32.
  35. Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007;110(4):1092–7. doi: 10.1182/blood-2007-04-083501.
  36. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2007;22(1):14–22. doi: 10.1038/sj.leu.2404955.
  37. Barbui T, Finazzi G, Carobbio A, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization – essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120(26):5128–33. doi: 10.1182/blood-2012-07-444067.
  38. Jensen MK, De Nully B, Hasselbach OJ, et al. Incidence, clinical features and outcome of essential thrombocythaemia in a well defined geographical area. Eur J Haematol. 2000;65(2):132–9. doi: 10.1034/j.1600-0609.2000.90236.x.
  39. Michiels JJ, Van Genderen P, Lindemans JJ, et al. Erythromelalgic, Thrombotic and Hemorrhagic Manifestations in 50 Cases of Thrombocythemia. Leuk Lymphoma. 1996;22(s1):47–56. doi: 10.3109/10428199609074360.
  40. Alvarez-Larran, A, Cervantes F, Pereira A, et al. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood. 2010;116(8):1205–10. doi: 10.1182/blood-2010-01-263319.
  41. Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for Patients with Essential Thrombocythemia and a High Risk of Thrombosis. N Engl J Med. 1995;332(17):1132–7. doi: 10.1056/nejm199504273321704.
  42. Gisslinger H, Holowiecki J, Penka M, et al. Final Results of the ANAHYDRET-Study: Non-Inferiority of Anagrelide Compared to Hydroxyurea in Newly Diagnosed WHO-Essential Thrombocythemia Patients. Blood (ASH Annual Meeting Abstracts). 2008;112:661.
  43. Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea Compared with Anagrelide in High-Risk Essential Thrombocythemia. N Engl J Med. 2005;353(1):33–45. doi: 10.1056/nejmoa043800.
  44. Fruchtman SM, Mack K, Kaplan ME, et al. From efficacy to safety: a Polycythemia Vera Study group report on hydroxyurea in patients with polycythemia vera. Semin Hematol. 1997;34(1):17–23.
  45. Kiladjian JJ, Chomienne C, Fenaux P. Interferon-[alpha] therapy in bcr-abl-negative myeloproliferative neoplasms. Leukemia. 2008;22(11):1990–8. doi: 10.1038/leu.2008.280.
  46. Lengfelder E, Griesshammer M, Hehlmann R. Interferon-alpha in the Treatment of Essential Thrombocythemia. Leuk Lymphoma. 1996;22(Suppl 1):135–42. doi: 10.3109/10428199609074371.
  47. Quintas-Cardama A, Kantarjian H, Manshouri T, et al. Pegylated Interferon Alfa-2a Yields High Rates of Hematologic and Molecular Response in Patients With Advanced Essential Thrombocythemia and Polycythemia Vera. J Clin Oncol. 2009;27(32):5418–24. doi: 10.1200/jco.2009.23.6075.
  48. Quintas-Cardama A, Abdel-Wahab O, Manshouri T, et al. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon a-2a. Blood. 2013;122(6):893–901. doi: 10.1182/blood-2012-07-442012.
  49. Cassinat B, Verger E, Kiladjian J-J. Interferon Alfa Therapy in CALR-Mutated Essential Thrombocythemia. N Engl J Med. 2014;371(2):188–9. doi: 10.1056/nejmc1401255.
  50. Sacchi S, Tabilio A, Leoni P, et al. Interferon alpha-2b in the long-term treatment of essential thrombocythemia. Ann Hematol. 1991;63(4):206–9. doi: 10.1007/bf01703444.
  51. Langer C, Lengfelder E, Thiele J, et al. Pegylated interferon for the treatment of high risk essential thrombocythemia: results of a phase II study. Haematologica. 2005;90(10):1333–8.
  52. Mascarenhas J, Mesa R, Prchal J, et al. Optimal therapy for polycythemia vera and essential thrombocythemia can only be determined by the completion of randomized clinical trials. Haematologica. 2014;99(6):945–9. doi: 10.3324/haematol.2014.106013.
  53. Alvarado Y, Cortes J, Verstovsek S, et al. Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia. Cancer Chemother Pharmacol. 2003;51(1):81–6. doi: 10.1007/s00280-002-0533-4.
  54. Quintas-Cardama A, Verstovsek S. Spleen deflation and beyond: The pros and cons of Janus kinase 2 inhibitor therapy for patients with myeloproliferative neoplasms. Cancer. 2012;118(4):870–7. doi: 10.1002/cncr.26359.
  55. Santos FP.S, Verstovsek S. JAK2 Inhibitors: Are They the Solution? Clin Lymph Myel Leuk. 2011;11(Suppl 1):S28–S36. doi: 10.1016/j.clml.2011.02.007.
  56. Tibes R, Mesa RA. Myeloproliferative neoplasms 5 years after discovery of JAK2V617F: what is the impact of JAK2 inhibitor therapy? Leuk Lymphoma. 2011;52(7):1178–87. doi: 10.3109/10428194.2011.566952.
  57. Verstovsek S, Passamonti F, Rambaldi A, et al. Durable Responses with the JAK1/JAK2 Inhibitor, INCB018424, In Patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) Refractory or Intolerant to Hydroxyurea (HU). Blood (ASH Annual Meeting Abstracts). 2010;116(21):313.
  58. Moliterno AR, Roboz GJ, Carroll M, et al. An Open-Label Study of CEP-701 in Patients with JAK2 V617F-Positive Polycythemia Vera and Essential Thrombocytosis. Blood (ASH Annual Meeting Abstracts). 2008;112(11):99.
  59. Baerlocher GM, Leibundgut EO, Ayran C, et al. Imetelstat Rapidly Induces and Maintains Substantial Hematologic and Molecular Responses in Patients with Essential Thrombocythemia (ET) Who Are Refractory or Intolerant to Prior Therapy: Preliminary Phase II Results. Blood (ASH Annual Meeting Abstracts). 2012;120(21):179.
  60. Barosi G, Birgegard G, Finazzi G, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood. 2009;113(20):4829–33. doi: 10.1182/blood-2008-09-176818.
  61. Schmitt-Graeff A. Standardization of Bone Marrow Biopsy Reporting in Ph-CMPD. LeukemiaNet. 2013; WP9.6:1.
  62. Wolanskyj AP, Schwager SM, McClure RF, et al. Essential Thrombocythemia Beyond the First Decade: Life Expectancy, Long-term Complication Rates, and Prognostic Factors. Mayo Clin Proceed. 2006;81(2):159–66. doi: 10.4065/81.2.159.
  63. Cervantes F, Alvarez-Larran A, Talarn C, et al. Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients. Br J Haematol. 2002;118(3):786–90. doi: 10.1046/j.1365-2141.2002.03688.x.
  64. Verstovsek S, Mesa RA, Gotlib J, et al. Consistent Benefit of Ruxolitinib Over Placebo in Spleen Volume Reduction and Symptom Improvement Across Subgroups and Overall Survival Advantage: Results From COMFORT-I. Blood (ASH Annual Meeting Abstracts). 2011;118(21):278.
  65. Harrison CN, Kiladijan JJ, Al-Ali HK, et al. Results of a randomized study of the JAK inhibitor INC424 compared with best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF). J Clin Oncol (ASCO Meeting Abstracts). 2011;29:LBA6501.
  66. Struve S, Finazzi G, Doehner K, et al. Pregnancies in Patients with Philadelphia Negative Chronic Myeloproliferative Disorders: Interim Report of the European LeukemiaNet Data Base. Blood (ASH Annual Meeting Abstracts). 2008;112(11):2806.
  67. Passamonti F, Randi ML, Rumi E, et al. Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation. Blood. 2007;110(2):485–9. doi: 10.1182/blood-2007-01-071068.
  68. Barbui T, Barosi G, Birgegard G, et al. Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European LeukemiaNet. J Clin Oncol. 2011;29(6):761–70. doi: 10.1200/jco.2010.31.8436.
  69. Askie LM, Duley L, Henderson-Smart DJ, Stewart LA. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. The Lancet. 2007;369(9575):1791–8. doi: 10.1016/s0140-6736(07)60712-0.
  70. Bangerter M, Guthner C, Beneke H, et al. Pregnancy in essential thrombocythaemia: treatment and outcome of 17 pregnancies. Eur J Haematol. 2000;65(3):165–9. doi: 10.1034/j.1600-0609.2000.90214.x.
  71. Greer IA, Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood. 2005;106(2):401–7. doi: 10.1182/blood-2005-02-0626.
  72. Hunt BJ, Gattens M, Khamashta M, et al. Thromboprophylaxis with unmonitored intermediate-dose low molecular weight heparin in pregnancies with a previous arterial or venous thrombotic event. Blood Coagul Fibrinol 2003;14(8):735–9. doi: 10.1097/00001721-200312000-00007.
  73. Gris J-C, Mercier E, Quere I, et al. Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood. 2004;103(10):3695–9. doi: 10.1182/blood-2003-12-4250.
  74. Liebelt EL, Balk SJ, Faber W, et al. NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea. Birth Defects Research Part B. Devel Reprod Toxicol. 2007;80(4):259–366. doi: 10.1002/bdrb.20123.
  75. Fenaux P, Simon M, Caulier MT, et al. Clinical course of essential thrombocythemia in 147 cases. Cancer. 1990;66(3):549–56. doi: 10.1002/1097-0142(19900801)66:3<549::aid-cncr2820660324>3.0.co;2-6.

Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura Developed During Gestation: Literature Review and Case Report

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , , , , , ,

V.V. Voitsekhovskii1, L.B. Filatov2, A.V. Pivnik3, P.V. Avdonin4, T.V. Esenina5, A.G. Sudakov5

1 Amur State Medical Academy, 95 Gor’kogo str., Blagoveshchensk, Amur Oblast, Russian Federation, 675000

2 Yekaterinburg Consultative and Diagnostic Centre, 5 Suvorovskii per., Yekaterinburg, Sverdlov Oblast, Russian Federation, 620039

3 D.D. Pletnev Moscow Clinical Scientific and Practical Center under the Department of Healthcare, 86 sh. Entuziastov, Moscow, Russian Federation, 111123

4 N.K. Kol’tsov Institute of Developmental Biology, 26 Vavilova str., Moscow, Russian Federation, 119334

5 Amur Regional Clinical Hospital, 26 Voronkova str., Blagoveshchensk, Amur Oblast, Russian Federation, 675028

For correspondence: V.V. Voitsekhovskii, DSci, Associate Professor, 95 Gor’kogo str., Blagoveshchensk, Amur Oblast, Russian Federation, 675000; Tel: +7(4162)42-94-97; e-mail: voitsehovsckij@yandex.ru

For citation: Voitsekhovskii V.V., Filatov L.B., Pivnik A.V., Avdonin P.V., Esenina T.V., Sudakov A.G. Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura Developed During Gestation: Literature Review and Case Report. Klin. Onkogematol. 2014; 7(4): 587–598 (In Russ.).

ABSTRACT

This paper presents a literature review on state of art in issues of etiology, pathogenesis, clinical features and diagnosis of thrombotic thrombocytopenic purpura (ТТP or Moschcowitz’s disease). Data on a rare pathology of congenital ТТP (Upshaw—Schulman syndrome) and its manifestation during pregnancy are summarized. Various aspects of differential diagnosis for microangiopathic hemolytic anemia (МАHA), complicated issues in differential diagnosis for thrombotic microangiopathies (ТТP, hemolytic uremic syndrome, HELLP syndrome) during pregnancy are discussed. Specificity of clinical manifestations and differential diagnosis for acquired and congenital TTP in pregnant patients are considered. Issues of TTP treatment during pregnancy are exposed in detail.

Keywords: thrombotic thrombocytopenic purpura, congenital thrombotic thrombocytopenic purpura, Upshaw-Schulman syndrome, thrombotic microangiopathy, microangiopathic hemolytic anemia, ADAMTS-13, HELLP syndrome, pregnancy.

Accepted: October 3, 2014

Read in PDF (RUS)pdficon

REFERENCES

  1. Ahmed S., Siddiqui R.K., Siddiqui S.A. et al. HIV-associated thrombotic microangiopathy. Postgrad. Med. J. 2002; 78(923): 520–5.
  2. Moschcowitz E. An acute febrile pleiochromic anemia with hyaline thrombosis of the terminal arterioles and capillaries: an undescribed disease. Mount Sinai J. Med. 2003; 70(5): 353–5.
  3. Шлегель Н. Тромботическая тромбоцитопеническая пурпура: пато- генез и терапевтические подходы. Гематология и трансфузиология. 1998; 3: 24–6. [Shlegel’ N. Thrombotic thrombocytopenic purpura: pathogenesis and therapeutic approaches. Gematologiya i transfuziologiya. 1998; 3: 24–6. (In Russ.)]
  4. Camous L., Veyradier A., Darmon M. et al. Macrovascular thrombosis in critically ill patients with thrombotic micro-angiopathies. Intern. Emerg. Med. 2012 Oct 7. [Epub ahead of print] PMID: 23054401.
  5. Moake J.L., Rudy C.K., Troll J.H. et al. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N. Engl. J. Med. 1982; 307(23): 1432–5.
  6. Furlan M., Robles R., Lаmmle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood. 1996; 87(10): 4223–34.
  7. Tsai H.-M. Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion. Blood. 1996; 87(10): 4235–44.
  8. Furlan M., Robles R., Galbusera M. et al. Von Willebrand factor–cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N. Engl. J. Med. 1998; 339(22): 1578–84.
  9. Tsai H.-M., Lian E.Ch.-Y. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N. Engl. J. Med. 1998; 339(22): 1585–94.
  10. Fujikawa K., Suzuki H., McMullen Br., Chung D. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood. 2000; 98(6): 1662–6.
  11. Levy G.G., Nichols W.C., Lian E.C. et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001; 413(6855): 488–94.
  12. Bianchi V., Robles R., Alberio L. et al. Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura. Blood. 2002; 100(2): 710–3.
  13. Studt J.-D., Kremer Hovinga J.A., Alberio L. et al. Von Willebrand factor– cleaving protease (ADAMTS-13) activity in thrombotic microangiopathies: diagnostic experience 2001/2002 of a single research laboratory. Swiss. Med. Wkly. 2003; 133(23–24): 325–32.
  14. Wyrick-Glatzel J. Thrombotic thrombocytopenic purpura and ADAMTS-13: New insights into pathogenesis, diagnosis, and therapy. Lab. Med. 2004; 35(12): 733–40.
  15. George J.N., Terrell D.R., Swisher K.K., Vesely S.K. Lessons learned from the Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome Registry. J. Clin. Apheresis 2008; 23(4): 129–37.
  16. Terrell D.R., Williams L.A., Vesely S.K. et al. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J. Thromb. Haemost. 2005; 3(7): 1–5.
  17. Kremer Hovinga J.A., Vesely S.K., Terrell D.R. et al. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010; 115(8): 1500–11.
  18. Lotta L.A., Wu H.M., Musallam K.M., Peyvandi F. The emerging concept of residual ADAMTS13 activity in ADAMTS13-deficient thrombotic thrombocytopenic purpura. Blood Rev. 2013; 27(2): 71–6.
  19. George J.N., Chen Q., Deford C.C., Al-Nouri Z. Ten patient stories illustrating the extraordinarily diverse clinical features of patients with thrombotic thrombocytopenic purpura and severe ADAMTS13 deficiency. J. Clin. Apher. 2012; 27(6): 302–11.
  20. Zhan H., Streiff M.B., King K.E., Segal J.B. Thrombotic thrombocytopenic purpura at the Johns Hopkins Hospital from 1992 to 2008: clinical outcomes and risk factors for relapse. Transfusion. 2010; 50(4): 868–74.
  21. Медведев П.В., Пивник А.В., Гласко Е.Н., Прасолов Н.В. Описание случая тромботической тромбоцитопенической пурпуры. Проблемы гема- тологии. 1998; 3: 46–9. [Medvedev P.V., Pivnik A.V., Glasko E.N., Prasolov N.V. Report of a case of thrombotic thrombocytopenic purpura. Problemy gematologii. 1998; 3: 46–9. (In Russ.)]
  22. Филатов Л.Б., Спирин А.В. Тромботическая тромбоцитопеническая пурпура (описание двух случаев). Терапевтический архив. 2005; 77(7): 81–3. [Filatov L.B., Spirin A.V. Thrombotic thrombocytopenic purpura (description of 2 cases). Terapevticheskii arkhiv. 2005; 77(7): 81–3. (In Russ.)]
  23. Amorosi E.L., Ultmann J.E. Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine. 1966; 45(2): 139–60.
  24. Scully M., Yarranton H., Liesner R. et al. Regional UK TTP Registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br. J. Haematol. 2008; 142(5): 819–26.
  25. George J.N. How I treat patients with thrombotic thrombocytopenic purpura. Blood. 2010; 116(20): 4060–9.
  26. Wahla A.S., Ruiz J., Noureddine N. et al. Myocardial infarction in thrombotic thrombocytopenic purpura. A single center experience and literature review. Eur. J. Haematol. 2008; 81(4): 311–6.
  27. Patschan D., Witzke O., Duhrsen U. et al. Acute myocardial infarction in thrombotic microangiopathies – clinical characteristics, risk factors and outcome. Nephrol. Dial. Transplant. 2006; 21(6): 1549–54.
  28. Sane D.C., Streer N.P., Owen J. Myocardial necrosis in patients with thrombotic thrombocytopenic purpura: pathophysiology and rationale for specific therapy. Eur. J. Haematol. 2009; 82(2): 83–92.
  29. Rock G.A., Shumak K.Н., Buskard N.A. et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian apheresis study group. N. Engl. J. Med. 1991; 325(6): 393–7.
  30. Moake J.L. Thrombotic microangiopathies. N. Engl. J Med. 2002; 347(8): 589–600.
  31. Thompson C.E., Damon L.E., Ries C.A., Linker C.A. Thrombotic microangiopathies in the 1980s: clinical features, response to treatment, and the impact of the human immunodeficiency virus epidemic. Blood. 1992; 80(8): 1890–5.
  32. Филатов Л.Б. Тромботическая тромбоцитопеническая пурпура. В кн.: Редкие гематологические болезни и синдромы. Под ред. М.А. Волковой. М.: Практическая медицина, 2011: 32–51. [Filatov L.B. Thrombotic thrombocytopenic purpura. In: Volkova M.A., ed. Redkie gematologicheskie bolezni i sindromy. (Rare hematological diseases and syndromes.) Moscow: Prakticheskaya meditsina Publ.; 2011. pр. 32–51. (In Russ.)]
  33. Sadler J.E., Poncz M. Antibody-mediated thrombotic disorders: idiopathic thrombotic thrombocytopenic purpura and heparin-induced thrombocytopenia. In: Williams Hematology, 7th edition. McGraw-Hill Medical, 2007: 2031–54.
  34. Scully M., Hunt B.J., Benjamin S. et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br. J. Haematol. 2012; 158(3): 323–35.
  35. Tsai H.M. Thrombotic thrombocytopenic purpura and the atypical hemolytic uremic syndrome: an update. Hematol. Oncol. Clin. N. Am. 2013; 27(3): 565–84.
  36. Schulman I., Pierce M., Lukens A., Currimbhoy Z. Studies on thrombopoiesis. I. A factor in normal human plasma required for platelet production; chronic thrombocytopenia due to its deficiency. Blood. 1960; 16(1): 943–57.
  37. Upshaw J.D. Jr. Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia. N. Engl. J. Med. 1978; 298(24): 1350–2.
  38. Moatti-Cohen M., Garrec C., Wolf M. et al. Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura. Blood. 2012; 119(24): 5888–97.
  39. George J.N. Forecasting the future for patients with hereditary TTP. Blood. 2012; 120(2): 243–4.
  40. Mansouri Taleghani M., von Krogh A.S., Fujimura Y. et al. Hereditary thrombotic thrombocytopenic purpura and the hereditary TTP registry. Hamostaseologie. 2013; 33(2): 138–43.
  41. Fujimura Y., Matsumoto M., Isonishi A. et al. Natural history of UpshawSchulman syndrome based on ADAMTS13 gene analysis in Japan. J. Thromb. Haemost. 2011; 1: 283–301.
  42. Lotta L.A. Pathophysiology of Thrombotic Thrombocytopenic Purpura: the “Two-Hit” paradigm. Leiden University Press, 2012.
  43. Loirat C., Girma J.P., Desconclois C. et al. Thrombotic thrombocytopenic purpura related to severe ADAMTS13 deficiency in children. Pediatr. Nephrol. 2009; 24(1): 19–29.
  44. Martin J.N. Jr., Bailey A.P., Rehberg J.F. et al. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955–2006. Am. J. Obstet. Gynecol. 2008; 199(2): 98–104.
  45. Veyradier A., Stepanian A., Coppo P. ADAMTS 13, thrombotic thrombocytopenic purpura and pregnancy. Heredit. Genet. 2012: S1-002.
  46. Gerth J., Schleussner E., Kentouche K. et al. Pregnancy-associated thrombotic thrombocytopenic purpura. Thromb. Haemost. 2009; 101(2): 248–51.
  47. Fujimura Y., Matsumoto M., Kokame K. et al. Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients. Br. J. Haematol. 2009; 144(5): 742–54.
  48. Khanna A., McCullough P.A. Malignant hypertension presenting as hemolysis, thrombocytopenia, and renal failure. Rev. Cardiovasc. Med. 2003; 4(4): 255–9.
  49. Asherson R.A., Cervera R., de Groot P.G. et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus. 2003; 12(7): 530–4.
  50. Баркаган З.С. Геморрагические заболевания и синдромы. М.: Меди- цина, 1988. 528 с. [Barkagan Z.S. Gemorragicheskie zabolevaniya i sindromy. (Hemorrhagic diseases and syndromes.) Moscow: Meditsina Publ.; 1988. 528 p.]
  51. Besbas N., Karpman D., Landau D. et al. A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int. 2006; 70(3): 423–31.
  52. George J.N. Thrombotic thrombocytopenic purpura. N. Engl. J. Med. 2006; 354(18): 1927–35.
  53. Hunt L., Li X., James J. et al. Thrombotic thrombocytopenic purpura (TTP) and systemic lupus erythematosus (SLE): distinct but potentially overlapping syndromes. Blood (ASH Annual Meeting Abstracts). 2004; 104(11): Abstract 858.
  54. Nabhan C., Kwaan H.C. Current concepts in the diagnosis and management of thrombotic thrombocytopenic purpura. Hematol. Oncol. Clin. N. Am. 2003; 17(1): 177–99.
  55. Шифман Е.М. Преэклампсия. Эклампсия. HELLP-синдром. Петроза- водск: ИнтелТек, 2002. 432 с. [Shifman E.M. Preeklampsiya. Eklampsiya. HELLP-sindrom. (Preeclampsy. Eclampsy. HELLP-syndrome.) Petrozavodsk: IntelTek Publ.; 2002. 432 p.]
  56. Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy. Am. J. Obstet. Gynecol. 1982; 142(2): 159–67.
  57. McCrae K.R. Thrombocytopenia in Pregnancy. ASH Education Program Book. 2010; 1: 397–402.
  58. George J.N. How I treat patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Blood. 2000; 96(4): 1223–9.
  59. Fakhouri F., Roumenina L., Provot F. et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J. Am. Soc. Nephrol. 2010; 21(5): 859–67.
  60. Кирсанова Т.В., Меркушева Л.И., Козловская Н.А. и др. Атипичный гемолитико-уремический синдром при беременности: особенности течения, сложности диагностики, подходы к терапии. Акушерство и гине- кология. 2013; 6: 70–5. [Kirsanova T.V., Merkusheva L.I., Kozlovskaya N.A. et al. Atypical hemolyticouremic syndrome during pregnancy: its course, difficulties in diagnosing, treatment approaches. Akusherstvo i ginekologiya. 2013; 6: 70–5. (In Russ.)]
  61. Loirat C., Fremeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet. J. Rare Dis. 2011; 6: 60.
  62. Zschiedrich S., Prager E.P., Kuehn E.W. Successful treatment of the postpartum atypical hemolytic uremic syndrome with eculizumab. Ann. Intern. Med. 2013; 159(1): 76.
  63. Delmas Y., Bordes C., Loirat C. et al. Post-partum atypical haemolyticuraemic syndrome treated with eculizumab: terminal complement activity assessment in clinical practice. Clin. Kidney J. 2013; 6(2): 243–4.
  64. Keiser S.D., Boyd K.W., Rehberg J.F. et al. A high LDH to AST ratio helps to differentiate pregnancy-associated thrombotic thrombocytopenic purpura (TTP) from HELLP syndrome. J. Matern. Fetal. Neonatal. Med. 2012; 25(7): 1059–63.
  65. Feng S., Eyler S.J., Zhang Y. et al. Partial ADAMTS13 deficiency in atypical hemolytic uremic syndrome. Blood. 2013; 122(8): 1487–93.
  66. Scully M., Starke R., Lee R. et al. Successful management of pregnancy in women with a history of thrombotic thrombocytopaenic purpura. Blood Coagul. Fibrinolysis. 2006; 17(6): 459–63.
  67. George J.N., Vesely S.K., Terrell D.R. et al. The Oklahoma thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome Registry. Hamostaseologie. 2013; 33: 105–12.
  68. Raman R., Yang S., Wu H.M., Cataland S.R. ADAMTS13 activity and the risk of thrombotic thrombocytopenic purpura relapse in pregnancy. Br. J. Haematol. 2011; 153(2): 277–9.
  69. Allford S.L., Hunt B.J., Rose P. et al. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br. J. Haematol. 2003; 120(4): 556–73.
  70. Chakravarty E.F., Murray E.R., Kelman A., Farmer P. Pregnancy outcomes after maternal exposure to rituximab. Blood. 2011; 117(5): 1499–506.
  71. Coppo P., Bussel A., Charrier S. et al. High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Medicine (Baltimore). 2003; 82(1): 27–38.
  72. George J.N. Thrombotic thrombocytopenic purpura — hemolytic uremic syndrome Newsletter. TTP-HUS 1999; 5 August. http://moon.ouhsc.edu/ jgeorge/TTPNEWS5.htm
  73. Jin M., Casper T.C., Cataland S.R. et al. Relationship between ADAMTS-13 activity in clinical remission and the risk of TTP relapse. Br. J. Haematol. 2008; 141(5): 651–8.
  74. Sadler J.E., Moake J.L., Miyata T., George J.N. Recent advances in thrombotic thrombocytopenic purpura. ASH Education Program Book. 2004: 407–23.
  75. Sarode R., Bandarenko N., Brecher M.E. et al. Thrombotic thrombocytopenic purpura: 2012 American Society for Apheresis (ASFA) consensus conference on classification, diagnosis, management, and future research. J. Clin. Apher. 2013 Oct 17. PMID: 24136342. 76. Naik S., Mahoney D.H. Successful Treatment of Congenital TTP With a Novel Approach Using Plasma-derived Factor VIII. J. Pediatr. Hematol. Oncol. 2013; 35(7): 551–3.

Interdigitating dendritic cell sarcoma: case report and literature review

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , ,

P.A. Zejnalova1, А.I. Pavlovskaya1, T.T. Valiev2, and N.V. Kokosadze1

1 Clinical Oncology Research Institute, N.N. Blokhin Cancer Research Center, RAMS, Moscow, Russian Federation

2 Pediatric Oncology and Hematology Research Institute, N.N. Blokhin Cancer Research Center, RAMS, Moscow, Russian Federation

ABSTRACT

We present the literature data and the authors’ observation of interdigitating dendritic cell sarcoma (IDCS), a very rare tumor consisting of histiocytic and dendritic cells. Due to variability in clinical presentation with nodal and/or extranodal involvement and immunomorphological characteristics of this sarcoma, differential diagnosis with non-Hodgkin’s lymphomas, melanoma, follicular dendritic cell sarcoma, and Langerhans cell histiocytosis is necessary. Here, we describe a clinical case of IDCS with cervical lymph node involvement and successful treatment with a CHOP program and subsequent irradiation. No generally accepted treatment strategy exists so far. Currently used methods include surgery, irradiation, and chemotherapy, but treatment outcomes need to be optimized.

Keywords: Interdigitating dendritic cell sarcoma, diagnosis, treatment.

Read in PDF (RUS) pdficon

 REFERENCES

  1. Takahashi K., Asagoe K., Zaishun J. et al. Heterogeneity of dendritic cells in human superficial lymph node in vitro maturation of immature dendritic cells into mature or activated interdigitating reticulum cell sarcoma. Am. J. Pathol. 1998; 153: 745–55.
  2. Pileri S.A., Grogan T.M., Harris N.L. et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 2002; 41: 1–29.
  3. Hye-Suk Han, Ok-Jun Lee, Sung-nam Lim et al. Extranodal interdigitating dendritic cell sarcoma presenting in a pleura: a case report. J. Korean Med. Sci. 2011; 26: 304–7. 4. Vasef M.A., Zaatari G.S., Chan W.C. et al. Dendritic cell tumors associated with low-grade B-cell malignances: report of three cases. Am. J. Clin. Pathol. 1995; 104: 696–701.
  4. Radovic S., Doric M., Zujo H. et al. Interdigitating dendritic cell sarcoma of the liver and lung: a case report with morphohological and immunohistochemical features of tumor. Bosn. J. Basic Med. Sci. 2012; 12: 203–6.
  5. Efune G., Sumer B.D., Sarode V.R. et al. Interdigitating dendritix cell sarcoma of the parotid gland: case report and literature review. Am. J. Otolaryngol. 2009; 30: 264–8.
  6. Kawachi K., Nakatani Y., Inayama Y. et al. Interdigitating dendritic cell sarcoma of the spleen: report of a case with a review of the literature. Am. J. Surg. Pathol. 2002; 26: 530–7.
  7. Luk I.S., Shek T.W., Tang V.W. et al. Interdigitating dendritic cell tumor of the testis: a novel testicular spindle cell neoplasm. Am. J. Surg. Pathol. 1999; 23: 1141–8.
  8. Rupar G., Beham-Schmid C., Galle G. et al. Interdigitating dendritic cell sarcoma of urinary bladder mimicking large intravesical calculus. Urology 2005; 66: 1109.
  9. Banner B., Beauchamp M.L., Liepman M. et al. Interdigitating reticulum — cell sarcoma of the intestine: a case report and review of the literature. Diagn. Cytopathol. 1997; 17: 216–22.
  10. Androulaki A., Giaslakiotis K., Lazaris A.C. Interdigitating dendritic cell sarcoma/tumour of the tonsil. Br. J. Haematol. 2005; 131: 415.
  11. Gaertner E.M., Tsokos M., Derringer G.A. et al. Interdigitating dendritic cell sarcoma. Am. J. Clin. Pathol. 2001; 115: 589–97.
  12. Zhou J., Zhou W., Bai C. et al. Interdigitating dendritic cell sarcoma: case report with review of the literature. Onkologie 2011; 34: 634–7.
  13. Barwell N., Howatson R., Jackson R. et al. Interdigitating dendritic cell sarcoma of salivary gland associated lymphoid tissue not associated with HHV-8 or EBV infection. J. Clin. Pathol. 2004; 57: 87–9.
  14. Kunihiko Maeda, Tomoko Takahashi, Chihiro Saitoh et al. Interdigitating cell sarcoma. J. Clin. Exp. Hematopathol. 2005; 45(1): 37–44.
  15. Sonoko Ishihara, Yumi Honda, Tsuguharu Asato et al. Interdigitating dendritic cell sarcoma of the ileum recurred in multiple lymph nodes and duodenum three years after operation without chemotherapy. Pathol. Res. Pract. 2010; 206: 514–8.
  16. Sun Wook Han, Zi Sun Kim, Hyuk Moon Kim et al. Interdigitating dendritic cell sarcoma occured alone in axilla. J. Korean Surg. Soc. 2012; 82: 330–4.
  17. Павловская А.И., Соколова И.Н. Саркома из интердигитирующих дендритных клеток. Арх. патол. 2010; 72(3): 30–2. [Pavlovskaya A.I., Sokolova I.N. Sarkoma iz interdigitiruyushchikh dendritnykh kletok (Interdigitating dendritic cell sarcoma. In: Arch. of Pathol.). Arkh. patol. 2010; 72(3): 30–2.]
  18. Cossu A., Deiana A., Lissia A. et al. Synchronous interdigitating dendritic cell sarcoma and B-cell small lymphocytic lymphoma in a lymph node. Arch. Pathol. Lab. Med. 2006; 130: 544–7.
  19. Pillay K., Solomon R., Daubenton J.D. et al. Interdigitating dendritic cell sarcoma: a report of four paediatric cases and review of literature. Histopathology 2004; 44: 283–91.
  20. Наssan Kanaan, Jaudah Al-Maghrabi, Ayman Linjawi et al. Interdigitating Dendritic cell sarcoma of the duodenum with rapidly fatal course. Arch. Pathol. Lab. Med. 2006; 130: 205–8.
  21. Kairouz S., Hashash J., Kabbara W. et al. Dendritic cell neoplasms: an overview. Am. J. Hematol. 2007; 82: 924–8.
  22. Fonseca R., Yamakawa M., Nakamura S. et al. Follicular dendritic cell sarcoma and interdigitating reticulum cell sarcoma: a review. Am. J. Hematol. 1998; 59: 161–7.
  23. van den Oord J.J., de Wolf-Peeters C., de Vos R. et al. Sarcoma arising from interdigitating reticulum cells: report of a case, studied with light and electron mycroscopy, and enzyme and immunohistochemistry. Histopathology 1986; 10: 509–23.
  24. Махонова Л.А., Валиев Т.Т. Интердигитирующая саркома из ден- дритных клеток. В кн.: Детская онкология. Национальное руководство. Под ред. М.Д. Алиева, В.Г. Полякова и др. М.: Практическая медицина, 2012: 419–20. [Makhonova L.A., Valiyev T.T. Interdigitiruyushchaya sarkoma iz dendritnykh kletok. V kn.: Detskaya onkologiya. Natsionalnoye rukovodstvo. Pod red. M.D. Aliyeva, V.G. Polyakova i dr. (Interdigitating dendritic cell sarcoma. In: Pediatric oncology. National manual. Ed. by M.D. Aliyev et al.). M.: Prakticheskaya meditsina, 2012: 419–20]