LYMPHOID TUMORS

Rare Disease — Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma: Literature Review and Own Data

LYMPHOID TUMORS , , , ,

E.A. Demina1, G.S. Tumyan1, A.A. Chekan1, M.Yu. Kichigina1, A.S. Antipova1, N.A. Probatova1, A.I. Pavlovskaya1, N.V. Kokosadze1, A.M. Kovrigina2, O.P. Trofimova1, E.A. Osmanov1

1 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: E.A. Demina, DSci, Professor, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-90-89; e-mail: drdemina@yandex.ru

For citation: Demina E.A., Tumyan G.S., Chekan A.A., Kichigina M.Yu., Antipova A.S., Probatova N.A., Pavlovskaya A.I., Kokosadze N.V., Kovrigina A.M., Trofimova O.P., Osmanov E.A. Rare Disease — Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma: Literature Review and Own Data. Klin. Onkogematol. 2014; 7(4): 522–532 (In Russ.).

ABSTRACT

Nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) is a rare disorder; it constitutes only 5 % of all cases of Hodgkin’s lymphoma (the morbidity rate is 1.5 per one million). The disease differs from classical Hodgkin’s lymphoma (cHL) in both immunohistochemical (marked CD20 expression in LP cells) and clinical features (prevalence of the early stage disease, indolent course with delayed relapses and trends toward transformation into diffuse large B cell lymphoma). Since the number of patients in prospective NLPHL-focused trials is limited, treatment algorithms have been based on retrospective data; these are usually obtained from cHL and indolent B cell lymphoma treatment strategies. Patients rarely die from NLPHL; in fact, secondary malignancies and other treatment related toxicities generally contribute to overall mortality. Over the past decade, there has been a series of NLPHL-related publications describing prescription of rituximab for newly diagnosed diseases and for relapses, including patients at high risk of diseases transformation. Besides, the role of the “wait and watch”, radiation treatment, and chemotherapy has been discussed. Our own experience in the use of rituximab in NLPLH patients demonstrated its efficacy at different stages and at different phases of the disease.

Keywords: nodular lymphocyte-predominant Hodgkin’s lymphoma, diagnosis, clinical characteristics, treatment, rituximab.

Accepted: September 8, 2014

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REFERENCES

  1. Jackson H., Parker F. Hodgkin’s disease II. Pathology. N. Engl. J. Med. 1944; 231: 35–44.
  2. Lukes R., Butler J., Hicks E. Natural history of Hodgkin’s disease as related to its pathological picture. Cancer. 1966; 19: 317–44.
  3. Harris N.L., Jaffe E.S., Stein H. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994; 84: 1361–92.
  4. Jaffe E.S., Harris N.L., Stein H. et al. Pathology and genetics of tumors of hematopoietic and lymphoid tissues. Lyon: IARC Press, 2001: 240–3.
  5. Swerdlow S.H., Campo E., Harris N.L. et al. (eds.) WHO classification of tumors of hematopoietic and lymphoid tissues. Lyon: IARC Press, 2008.
  6. Diehl V., Sextro M., Franclin J. et al. Clinical presentation, course, and prognostic factors in lymphocyte predominant Hodgkin’s disease: report from European Task Force on Lymphoma (ETFL) Project on lymphocyte-predominant Hodgkin’s disease. J. Clin. Oncol. 1999; 17: 776–83.
  7. Saarinen S., Pukkala E., Vahteristo P. et al. High Familial Risk in Nodular Lymphocyte-Predominant Hodgkin Lymphoma. JCO. 2013; 31(7): 938–43.
  8. Mason D.Y., Banks P.M., Chan J. et al. Nodular lymphocyte-predominant Hodgkin’s disease. A distinct clinicopathological entity. Am. J. Surg. Pathol. 1994; 18: 526–30.
  9. Engert A., Horning S.J. (eds.) Hodgkin Lymphoma: A Comprehensive Update on Diagnostics and Clinics (Hematologic Malignancies). Springer, 2011.
  10. Ковригина А.М., Пробатова Н.А. Лимфома Ходжкина и крупнокле- точные лимфомы. Медицинское информационное агентство, 2007. [Kovrigina A.M., Probatova N.A. Limfoma Khodzhkina i krupnokletochnye limfomy. (Hodgkin’s lymphoma and larg cell lymphomas.) Meditsinskoe informatsionnoe agentstvo Publ.; 2007.]
  11. Nogova L., Reineke T., Brillant C. et al. Lymphocyte-predominant and classical Hodgkin’s lymphoma: a comprehensive analysis from the German Hodgkin Study Group. J. Clin. Oncol. 2008; 26: 434–9.
  12. Лимфома Ходжкина. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. Современная онкология. Экстравыпуск. 2013: 11–5. [Poddubnaya I.V., Savchenko V.G., eds. Limfoma Khodzhkina. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. (Hodgkin’s lymphoma. Russian clinical guidelines in diagnosis and treatment of lymphoproliferative disorders.) Sovremennaya onkologiya. Additional release; 2013. pр. 11–5.]
  13. Fanale M. Lymphocyte-predominant Hodgkin lymphoma: what is the optimal treatment? Hematology (EHA 2013 Education book). 2013: 406–16.
  14. Kuppers R., Rajewsky K., Zhao M. et al. Hodgkin disease: Hodgkin and Reed–Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B-cells at various stages of development. Proc. Natl. Acad. Sci. USA. 1994; 91: 10962–6.
  15. Marafioti T., Hummel M., Anagnostopoulos I. et al. Origin of nodular lymphocyte-predominant Hodgkin’s disease from a clonal expansion of highly mutated germinal center B-cells. N. Engl. J. Med. 1997; 337(7): 453–8.
  16. Isaacson P.G. Malignant lymphomas with a follicular growth pattern. Histopathology. 1996; 28(6): 487–95.
  17. Brune V., Tiacci E., Pfeil I. et al. Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis. J. Exp. Med. 2008; 205(10): 2251–68.
  18. Mottok A., Renne C., Willenbrock K. et al. Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAC2 expression and activation of STAT6. Blood. 2007; 110(9): 3387–90.
  19. Schumacher A.M., Schmitz R., Brune V. et al. Mutations in the genes coding for den NJ-kB regulation factors IkBa and A20 are uncommon in nodular lymphocyte-predominant Hodgkin lymphoma. Haematologica. 2010; 95: 153–7.
  20. Liso A., Capello D., Marafiotti T. et al. Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma. Blood. 2006; 108(3): 1013–20.
  21. Rahemtullah A., Reichard K.K., Preffer F.I. et al. A double-positive CD4+CD8+ T-cells population is commonly found in nodular lymphocyte predominant Hodgkin lymphoma. Am. J. Clin. Pathol. 2006; 125(5): 153–7.
  22. Henry-Amar M. Second cancer after treatment for Hodgkin’s disease: a report from the International Database on Hodgkin’s disease. Ann. Oncol. 1992; 3(Suppl. 4): 117.
  23. Saad J., Sirop S.J., Habermann T.M. et al. Diffuse Large B-Cell Transformation in Nodular Lymphocyte Predominant Hodgkin Lymphoma: Incidence, Risk Factors and Outcomes After a Forty-Year Experience From a Single Institution. Blood (ASH Annual Meeting Abstracts). 2012; 120: 1525.
  24. Al-Mansour M., Connors J.M., Gascoyne R.D. et al. Transformation to Aggressive Lymphoma in Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma. J. Clin. Oncol. 2010; 28: 793–9.
  25. Bennett M.H., MacLennan K.A., Vaughan Hudson G. et al. Non-Hodgkin’s lymphoma arising in patients treated for Hodgkin’s disease in the BNLI: A 20- year experience—British National Lymphoma Investigation. Ann. Oncol. 1991; 2(Suppl. 2): 83–92.
  26. Orlandi E., Lazzarino M., Brusamolino E. et al. Nodular lymphocyte predominance Hodgkin’s disease: Long-term observation reveals a continuous pattern of recurrence. Leuk. Lymphoma. 1997; 26: 359–68.
  27. Wickert R.S., Weisenburger D.D., Tierens A. et al. Clonal relationship between lymphocytic predominance Hodgkin’s disease and concurrent or subsequent large-cell lymphoma of B lineage. Blood. 1995; 86: 2312–20.
  28. Hell K., Hansmann M.L., Pringle J.H. et al. Combination of Hodgkin’s disease and diffuse large cell lymphoma: An in situ hybridization study for immunoglobulin light chain messenger RNA. Histopathology. 1995; 27: 491–9.
  29. Greiner T.C., Gascoyne R.D., Anderson M.E. et al. Nodular lymphocytepredominant Hodgkin’s disease associated with large-cell lymphoma: Analysis of Ig gene rearrangements by V-J polymerase chain reaction. Blood. 1996; 88: 657–66.
  30. Sirop S.J., Habermann T.M., Macon W.R. et al. Diffuse Large B-Cell Transformation in Nodular Lymphocyte Predominant Hodgkin Lymphoma: Incidence, Risk Factors and Outcomes After a Forty-Year Experience From a Single Institution. Blood (ASH Annual Meeting Abstracts). 2012; 120(21): Abstract 1525.
  31. Farrell K., Mckay P., Leach M. Nodular Lymphocyte Predominant Hodgkin Lymphoma behaves as a Distinct Clinical Entity with Good Outcome: Evidence from 14 year Follow-up from the West of Scotland Cancer Network. Ann. Oncol. 2011; 22(Suppl. 4): Abstract 291.
  32. Pappa V.I., Norton A.J., Gupta R.K. et al. Nodular type of lymphocyte predominant Hodgkin’s disease. A clinical study of 50 cases. Ann. Oncol. 1995; 6(6): 559–65.
  33. Connors J.M. Lymphocyte predominant Hodgkin’s lymphoma. ASH (Education Program Book). 2001: 1: 187–90.
  34. Borg-Grech A., Radford J.A., Crowther D., Swindell R., Harris M. A comparative study of the nodular and diffuse variants of lymphocytepredominant Hodgkin’s disease. J. Clin. Oncol. 1989; 7(9): 1303–9.
  35. Regula D.P. Jr., Hoppe R.T., Weiss L.M. Nodular and diffuse types of lymphocyte predominance Hodgkin’s disease. N. Engl. J. Med. 1988; 318(4): 214–9.
  36. Crennan E., D’Costa I., Liew K.H. et al. Lymphocyte predominant Hodgkin’s disease: a clinicopathologic comparative study of histologic and immunophenotypic subtypes. Int. J. Radiat. Oncol. Biol. Phys. 1995; 31(2): 333–7.
  37. Hansmann M.L., Zwingers T., Boske A., Loffler H., Lennert K. Clinical features of nodular paragranuloma (Hodgkin’s disease, lymphocyte predominance type, nodular). J. Cancer Res. Clin. Oncol. 1984; 108(3): 321–30.
  38. Bodis S., Kraus M.D., Pinkus G. et al. Clinical presentation and outcome in lymphocyte-predominant Hodgkin’s disease. J. Clin. Oncol. 1997; 15(9): 3060–6.
  39. Pellegrino B., Terrier-Lacombe M.J., Oberlin O. et al. Lymphocytepredominant Hodgkin’s lymphoma in children: therapeutic abstention after initial lymph node resection — a study of the French Society of Pediatric Oncology. J. Clin. Oncol. 2003; 21: 2948–52.
  40. Murphy S.B., Morgan E.R., Katzenstein H.M. et al. Results of little for not treatment for lymphocyte-predominant Hodgkin disease in children and adolescents. J. Pediatr. Hematol. Oncol. 2003; 25: 684–7.
  41. Mauz-Koerholz С., Hasenclever D., Gorde-Grosjean S. et al. Surgical resection alone in children with limited stage lymphocyte predominant Hodgkin’s lymphoma — the experience of the EuroNet-PHL group [abstract]. Blood (ASH Annual Meeting Abstracts). 2006; 108(11): 2470.
  42. Appel B., Ehrich P., Chen L. et al. Treatment of pediatric stage IA lymphocyte-predominant Hodgkin’s lymphoma with surgical resection alone: A report from the Children’s Oncology Group. J. Clin. Oncol. 2012; 30: 9524.
  43. Biasoli I., Stamatoullas A., Meignin V. et al. Nodular, LymphocytePredominant Hodgkin’s Lymphoma. Cancer. 2010; 116: 631–9.
  44. Schlembach P., Wilder R., Jones D. et al. Radiotherapy alone for lymphocyte-predominant Hodgkin’s disease. Cancer J. 2002; 8(5): 377–83.
  45. Wirth A., Yuen K., Barton M. et al. Long-term outcome after radiotherapy alone for lymphocyte-predominant Hodgkin lymphoma: a retrospective multicenter study of the Australian Radiation Oncology Lymphoma Group. Cancer. 2005; 104(6): 1221–9.
  46. Chen R.C., Chin M.S., Ng A.K. et al. Early stage, lymphocyte-predominant Hodgkin’s lymphoma: patient outcomes from a large, single-institution series with long follow-up. J. Clin. Oncol. 2010; 28(1): 136–41.
  47. Nogova L., Reineke T., Eich H.T. et al. Extended field radiotherapy, combined modality treatment or involved field radiotherapy for patient with stage IA lymphocyte-predominant Hodgkin’s lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG). Ann. Oncol. 2005; 16(10): 1683–7.
  48. Eichenauer D.A., Fuchs M., Pluetschow A. et al. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2011; 118(16): 4363–5.
  49. Canellos G.P., Mauch P. What Is the Appropriate Systemic Chemotherapy for Lymphocyte-Predominant Hodgkin’s Lymphoma? J. Clin. Oncol. 2010; 28(1): е8.
  50. Fanale M.A., Lai C.M., McLaughlin P. et al. Outcomes of Nodular Lymphocyte Predominant Hodgkin’s Lymphoma (NLPHL) Patients Treated with R-CHOP. Blood (ASH Annual Meeting Abstracts). 2010; 116(21): Abstract 2812.
  51. Advani R.H., Hope R.T. How I treat lymphocyte predominant Hodgkin Lymphoma. Blood. 2013; 122(26): 4182–8.
  52. Karuturi M., Hosing C., Fanale M. et al. High-dose chemotherapy and autologous stem cell transplantation for nodular lymphocyte-predominant Hodgkin lymphoma. Biol. Blood Marrow Transplant. 2013; 19(6): 991–4.
  53. Bierman P., Naushad H., Loberiza F. et al. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) for lymphocyte predominant Hodgkin’s disease [abstract]. Blood. 2006; 108(11): Abstract 3061.
  54. Jackson C., Sirohi B., Cunningham D. et al. Lymphocyte-predominant Hodgkin lymphoma — clinical features and treatment outcomes from a 30-year experience. Ann. Oncol. 2010; 21(10): 2061–8.
  55. Eichenauer D.A., Fuchs M., Pluetschow A. et al. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2011; 118(16): 4363–5.
  56. Park H.C., Jung S.H., Ahn J.S. et al. Rituximab plus ifosfamide, carboplatin and etoposide for T-cell/histiocyte-rich B-cell lymphoma arising in nodular lymphocyte-predominant Hodgkin’s lymphoma. Case Rep. Oncol. 2012; 5(2): 413–9.
  57. Ekstrand B.C., Lucas J.B., Horwitz S.M. et al. Rituximab in lymphocytepredominant Hodgkin disease: results of a phase 2 trial. Blood. 2003; 101(11): 4285–9.
  58. Schulz H., Rehwald U., Morschhauser F. et al. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2008; 111(1): 109–11.
  59. Advani R.H., Buggy J.J., Sharman J.P. et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/ refractory B-cell malignancies. J. Clin. Oncol. 2013; 31(1): 88–94.
  60. Advani R.H., Horning S.J., Hope RT. et al. Mature results of a Phase II Study of Rituximab Therapy for Nodular Lymphocyte-Predominant Hodgkin Lymphoma. J. Clin. Oncol. 2014; 32(9): 912–8.

Association between HLA-DRB1 alleles and response to imatinib in chronic myeloid leukemia

LYMPHOID TUMORS ,

E.G. Ovsyannikova1, I.L. Davydkin2, E.A. Popov1, L.V. Zaklyakova1, and B.N. Levitan1

1 Astrakhan State Medical Academy, RF Ministry of Health, Astrakhan, Russian Federation

2 Research Institute of Hematology, Transfusiology, and Intensive Care, Samara State Medical University, RF Ministry of Health, Samara, Russian Federation

ABSTRACT

The article presents analysis of association between the HLA-DRB1 gene alleles and the response to imatinib in the patients with Ph-positive chronic myeloid leukemia (Ph+ CML). HLA class II alleles, DRB1 locus, were determined using PCR-SSP. The predictors of optimal response to imatinib in 3 to 18-months treatment of CML are HLA-DRB1*16(02), HLA-DRB1*17(03), and HLA-DRB1*08 specificities. Immunogenetic markers of imatinib treatment failure are HLA-DRB1*11(05), HLA-DRB1*12(05), and HLA-DRB1*14(06) alleles. The results obtained can be used for the development of individual long-term prognosis for chronic myeloid leukemia and optimization of the treatment choice.

Keywords: chronic myeloid leukemia, HLA-DRB1, imatinib, prognosis.

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REFERENCES

  1. Deininger M., O’Brien S.G., Guilhot F. et al. International randomized study of interferon vs STI571 (IRIS) 8-year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood 2009; 114: 1126 (abstr.).
  2. Apperley J.F. Part I: Mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 2007; 8: 1018–29.
  3. Soverini S., Hochhaus A. et al. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood 2011; 18(5): 1208–15.
  4. Li L., Wang L., Li L. et al. Activation of p53 by SIRT1 Inhibition Enhances Elimination of CML Leukemia Stem Cells in Combination with Imatinib. Cancer Cell 2012; 21: 266–81.
  5. Ferrandiz N., Caraballoa J. M., Albajara M. et al. p21(Cip1) confers resistance to imatinib in human chronic myeloid leukaemia с Cancer Lett. 2010; 292(1): 133–9.
  6. Guillem V., Amat P., Cervantes F. et al. Functional polymorphisms in SOCS1 and PTPN22 genes correlate with the response to imatinib treatment in newly diagnosed chronic-phase chronic myeloid leukemia. Res. 2012; 36(2): 174–81.
  7. Marin D., Gabriel I.H., Ahmad S. et al. KIR2DS1 genotype predicts for complete cytogenetic response and survival in newly diagnosed chronic myeloid leukemia patients treated with imatinib. Leukemia 2012; 26(2): 296–302.
  8. Хаитов P.M., Дедов И.И., Болдырева М.Н. Новые представления о функции главного комплекса генов иммунного ответа человека. Мол. мед. 2006; 3: 47–51. [Khaitov P.M., Dedov I.I., Boldyreva M.N. Novye predstavleniya o funktsii glavnogo kompleksa genov immunnogo otveta cheloveka (New concepts of function of human major immune response gene complex. In: Mol. med.). Mol. med. 2006; 3: 47–51.]
  9. Короткова И.Ю. Клиническая иммуногенетика заболеваний, злокачественных новообразований и хронических воспалительных процессов: Дис. ¼ д-ра мед. наук. Новосибирск, 2007. [Korotkova I.Yu. Klinicheskaya immunogenetika zabolevaniy, zlokachestvennykh novoobrazovaniy i khronicheskikh vospalitelnykh protsessov: Dis. ¼ d-ra med. nauk (Clinical immunogenetics of diseases, malignancies, and chronic inflammatory processes. Dissertation for the degree of DSci). Novosibirsk, 2007.]
  10. Соколова Ю.В. Роль полиморфизма генов иммуноглобулинподобных рецепторов киллерных клеток, их лигандов и генов HLA в патогенезе и прогнозе множественной миеломы: Автореф. дис. ¼ канд. биол. наук. СПб., 2012. [Sokolova Yu.V. Rol polimorfizma genov immunoglobulinpodobnykh retseptorov killernykh kletok, ikh ligandov i genov HLA v patogeneze i prognoze mnozhestvennoy miyelomy: Avtoref. dis. ¼ kand. biol. nauk (Role of Ig-like killer cell receptor gene polymorphism, their ligands, and HLA genes in pathogenesis and prognosis of multiple myeloma. Author’s summary of dissertation for the degree of PhD). Spb., 2012.]
  11. Villalobos C., Rivera S., Weir-Medina J. et al. Association of HLA class I and leukemia in mestizo patients of the state of Zulia, Venezuela. Clin. 2003; 44(4): 283–9.
  12. Wei L., Xiao L., Wu X.Y. et al. Expression and analysis of HLA-A, B and DRB1 genes in patients with chronic myelogenous leukemia in Guangdong area. Journal of experimental hematology. Chinese Assoc. Pathophysiol. 2008; 16(4): 915–8.
  13. Naugler C., Liwski R. HLA risk markers for chronic myelogenous leukemia in Eastern Canada. Lymphoma 2009; 50(2): 254–9.
  14. Хамаганова Е.Г. Активная вакцинация при хроническом миелолейкозе. Гематол. и трансфузиол. 2008; 53(2): 42–8. [Khamaganova Ye.G. Aktivnaya vaktsinatsiya pri khronicheskom miyeloleykoze [Active immunization in chronic myelogenous leukemia. In: Hematol. & transfuziol.). Gematol. i transfuziol. 2008; 53(2): 42–8.]
  15. Mannering S.I., Mckenzie J.L, Feamley D.В., Hart D.N.J. HLA-DRlrestricted bcr-abl (b3a2)-specific CD4+ T lymphocytes respond to dendritic cells pulsed with b3а2 peptide and antigen presenting cells exposed to b3a2- containing cell lysates. Blood 1997; 90: 290–7.
  16. Хамаганова Е.Г., Зарецкая Ю.М. Молекулярные механизмы ассоциаций HLA-системы с резистентностью к развитию хронического миелолейкоза. Гематол. и трансфузиол. 2006; 1: 12–7. [Khamaganova Ye.G., Zaretskaya YU.M. Molekulyarnye mekhanizmy assotsiatsiy HLA-sistemy s rezistentnostyu k razvitiyu khronicheskogo miyeloleykoza (Molecular mechanisms of associations between HLA system and resistance to development of chronic myelogenous leukemia. In: Hematol. & transfuziol.). Gematol. i transfuziol. 2006; 1: 12–7.]
  17. Bosch ten G.J., Kessler J.H., Joosten A.C. et al. A BCR-ABL oncoprotein p210 b2а2 fusion region sequence is recognized by HLA-DR2a-restricted cytotoxic T lymphocytes and presented by HLA-DR-matched cells transfected with an L-li (b2а2) construct. Blood 1999; 94: 1038–45.
  18. Максимов О.Д., Зайцев Г.А., Бутина Е.В. Распределение HLA-маркеров при хроническом лимфолейкозе. Гематол. и трансфузиол. 2003; 1: 19–22. Maksimov O.D., (Zaytsev G.A., Butina Ye.V. Raspredeleniye HLA-markerov pri khronicheskom limfoleykoze [HLA markers distribution in chronic lymphocytic leukemia. In: Hematol. & transfuziol.). Gematol. i transfuziol. 2003; 1: 19–22.]
  19. Сенькина Е.А. Клиническое значение полиморфизма HLA- специфичностей классов I, II и иммунных нарушений при множественной миеломе: Автореф. дис. ¼ канд. мед. наук. СПб., 2010. [Senkina Ye.A. Klinicheskoye znacheniye polimorfizma HLA-spetsifichnostey klassov I, II i immunnykh narusheniy pri mnozhestvennoy miyelome: Avtoref. dis. ¼ kand. med. nauk (Clinical significance of HLA class I and class II specificity polymorphism and immunological disorders in multiple myeloma]. Author’s summary of dissertation for the degree of PHD). SPb., 2010.]
  20. Shi J., Tricot G.J., Garg T.K. et al. Bortezomib down-regulates the cell surface expression of HLA-class I and enhances natural killer cell-mediated lysis of myeloma. Blood 2008; 111(3): 1309–17.
  21. Овсянникова Е.Г., Исрапилова З.М., Заклякова Л.В. Анализ распре- деления аллелей гена HLA-DRB1 у больных хроническим миелолейкозом. Науч. ведомости Белгородского гос. ун-та. 2011; 22 (117): 110–4. [Ovsyannikova Ye.G., Israpilova Z.M., Zaklyakova L.V. Analiz raspredeleniya alleley gena HLA-DRB1 u bolnykh khronicheskim miyeloleykozom (Analysis of HLA DRB1 allele distribution in patients with chronic myelogenous leukemia. In: Scientif. bulletin of Belgorod St. Univers.). Nauch. vedomosti Belgorodskogo gos. un-ta. 2011; 22 (117): 110–4.]
  22. Овсянникова Е.Г., Исрапилова З.М., Заклякова Л.В., Попов Е.А. Аллельный полиморфизм гена HLA-DRB1 при хроническом миелолейкозе. Фундамент. исслед. 2011; 10(3): 538–54. [Ovsyannikova Ye.G., Israpilova Z.M., Zaklyakova L.V., Popov Ye.A. Allelnyy polimorfizm gena HLA-DRB1 pri khronicheskom miyeloleykoze (HLA DRB1 allele polymorphism in chronic myelogenous leukemia. In: Fundament. stud.). Fundament. issled. 2011; 10(3): 538–54.]
  23. Baccarani M., Cortes J., Pane F. et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. Clin. Oncol. 2009; 27(35): 6041–51.
  24. Сароянц Л.В., Болдырева М.Н., Гуськова И.А. и др. Иммуногенетические маркеры предрасположенности к лепре у русских жителей Астрахан- ского региона. Иммунология 2005; 5: 263–7. [Saroyants L.V., Boldyreva M.N., Guskova I.A. i dr. Immunogeneticheskiye markery predraspolozhennosti k lepre u russkikh zhiteley Astrakhanskogo regiona (Immunogenetic markers of susceptibility to leprosy in Russian population of Astrakhan’ region. In: Immunology). Immunologiya 2005; 5: 263–7.]

Current therapies for AL amyloidosis: literature review and our data

LYMPHOID TUMORS , , ,

A.G. Smirnova1, S.N. Bondarenko1, A.A. Kisina2, A.V. Smirnov2, A. Tsander 3, and B.V. Afanasyev1

1 R.M. Gorbacheva Institute of Pediatric Hematology and Transplantology, I.P. Pavlov State Medical University, Saint Petersburg, Russian Federation

2 Research Institute of Nephrology, I.P. Pavlov State Medical University, Saint Petersburg, Russian Federation

3 Universitare Transplantations-Centrum, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany

ABSTRACT

AL amyloidosis is a relatively rare condition belonging to plasma cell dyscrasias with very heterogeneous clinical presentation and poor prognosis. This article presents a brief description of AL amyloidosis, current therapies, and our own statistics on new combination therapy outcomes. We included 46 patients with confirmed AL amyloidosis who received autologous stem cell transplantation and standard combination chemotherapy, including melphalan + dexamethasone or bortezomib + dexamethasone.

Keywords: AL amyloidosis, therapy, hematopoietic stem cell transplantation, melphalan, bortezomib.

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REFERENCES

  1. Falk R.H., Comenzo R.L., Skinner M. The systemic amyloidoses. N. Engl. J. Med. 1997; 337: 898–909.
  2. Kyle R.A., Gertz M.A. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin. Hematol. 1995; 32: 45–59.
  3. Dispenzieri A., Gertz M.A., Kyle R.A. et al. Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2004; 104: 1881–7.
  4. Dispenzieri A., Gertz M.A., Kyle R.A. et al. Serum cardiac troponins and N-terminal pro-brain natriureticpeptide: a staging system for primary systemic amyloidosis. J. Clin. Oncol. 2004; 22: 3751–7.
  5. Palladini G., Merlini G. Transplantation vs. conventional-dose therapy for amyloidosis. Curr. Opt. Oncol. 2011; 23: 214–20.
  6. Palladini G., Lavatelli F., Russo P. et al. Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood 2006; 107: 3854–8.
  7. Bochtler T., Hegenbart U., Heiss C. et al. Evaluation of the serum-free light chain test in untreated patients with AL amyloidosis. Haematologica 2008; 93: 459–62.
  8. Dispenzieri A., Lacy M.Q., Katzmann J.A. et al. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2006; 107: 3378–83.
  9. Kumar S., Dispenzieri A., Katzmann J.A. et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood 2010; 116(24): 5126–9.
  10. Lachmann H.J., Gallimore R., Gillmore J.D. et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br. J. Haematol. 2003; 122: 78–84.
  11. Gertz M.A. Definition of organ involvement and response to treatment in AL amyloidosis: An updated consensus opinion. Amyloid 2010; 17(Suppl. 1): 48–49, abstr. CP-B.
  12. Leung N., Dispenzieri A., Lacy M.Q. et al. Severity of Baseline Proteinuria Predicts Renal Response in Immunoglobulin Light Chain–Associated Amyloidosis after Autologous Stem Cell Transplantation. Clin. J. Am. Soc. Nephrol. 2007; 2: 440–4.
  13. Kyle R.A., Gertz M.A., Greipp Ph.R. et al. Long-term survival (10 years or more) in 30 patients with AL amyloidosis. Blood 1999; 93: 1062–6.
  14. Kyle R.A., Greipp, P.R. Primary systemic amyloidosis: comparison of melphalan and prednisone versus placebo. Blood 1978; 52: 818–27.
  15. Kyle R.A., Greipp, P.R., O’Fallon M. Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases. Blood 1986; 68: 220–4.
  16. Kyle R.A., Gertz M.A., Greipp P.R. et al. A trial of three regimen for primary amyloidosis: colchicine alone, melphalan and prednisolone, and melphalan, prednisolone, and colchicine. N. Engl. J. Med. 1997; 336: 1202–7.
  17. Skinner M., Anderson J., Simms R. et al. Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only. Am. J. Med. 1996; 100: 290–8.
  18. Dhodapkar M.V., Hussein M.A., Rasmussen E. et al. Clinical efficacy of high-dose dexamethasone with maintenance dexamethasone/alpha interferon in patients with primary systemic amyloidosis: results of United States Intergroup Trial Southwest Oncology Group (SWOG) S9628. Blood 2004; 104: 3520–6.
  19. Palladini G., Perfetti V., Obici L. et al. Association of melphalan and highdose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood 2004; 103: 2936–8.
  20. Dispenzieri A., Lacy M.Q., Rajkumar S.V. et al. Poor tolerance of thalidomide in patients with primary systemic amyloidosis. Amyloid 2003; 10: 257–61.
  21. Palladini G., Perfetti V., Perlini S. et al. The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL). Blood 2005; 105: 2949–51.
  22. Wechalekar А., Goodman H.J.B., Lachmann H.J. et al. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood 2007; 109: 457–64.
  23. Dispenzieri A., Lacy M.Q., Zeldenrust S.R. et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood 2007; 109: 465–70.
  24. Sanchorawala V., Wright D.G., Rosenzweig M. et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood 2007; 109: 492–6.
  25. Dispenzieri A., Gertz M.A., Hayman S.R. et al. Pomalidomide and dexamethasone for previously treated AL: a phase 2 study. Amyloid J. Protein Folding Dis. 2010; 17: 87.
  26. Dispenzieri A., Buadi F., Laumann K. et al. The activity of pomalidomide in patients with immunoglobulin light chain amyloidosis. Blood 2012; 119: 5397–404.
  27. Wechalekar A., Lachmann H.J., Offer M. et al. Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal disease. Haematologica 2008; 93(2): 295–8.
  28. Kastritis E., Anagnostopoulos A., Roussou M. et al. Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone. Haematologica 2007; 92: 1351–8.
  29. Zonder J.A., Sanchorawala V., Snyder R.M. et al. Melphalan and Dexamethasone Plus Bortezomib Induces Hematologic and Organ Responses in AL-Amyloidosis with Tolerable Neurotoxicity. Blood 2009; 114: 310–1.
  30. Zonder J., Sanchorawala V., Snyder R. et al. Rapid haematologic and organ responses in patients with AL amyloid treated with bortezomib plus melphalan and dexamethasone. Amyloid J. Protein Folding Dis. 2010; 17: 86–7.
  31. Mikhael J.R., Schuster S.R., Jimenez-Zepeda V.H. et al. The Combination of Cyclophosphamide-Bortezomib-Dexamethasone (CYBOR-D) Is a Highly Effective and Well Tolerated Regimen that Produces Rapid and Complete Hematological Response In Patients with AL Amyloidosis. ASH Annual Meeting Abstracts 2010; 116: 3063.
  32. Comenzo R.L., Vosburgh E., Simms R.W. et al. Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: One-year follow-up in five patients. Blood 1996; 88: 2801–6.
  33. Comenzo R.L., Vosburgh E., Falk R.H. et al. Dose intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients. Blood 1998; 91: 3662–70.
  34. Moreau P., Leblond V., Bourquelot P. et al. Prognostic factors for survival and response after high-dose therapy and autologous stem cell transplantation in systemic AL amyloidosis: a report on 21 patients. Br. J. Haematol. 1998; 101: 766–9.
  35. Gillmore J.D. High-dose melphalan and stem cell rescue for AL amyloidosis. In: Amyloid and Amyloidosis. Ed. by R.A. Kyle, M.A. Gertz). Pearl River: Parthenon Publishing, 1999: 102–4.
  36. Gertz M.A., Lacy M.Q., Gastineau D.A. et al. Blood stem cell transplantation as therapy for primary systemic amyloidosis (AL). Bone Marrow Transplant. 2000; 26: 963–9.
  37. Sanchorawala V. An overview of the use of high dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplant. 2001; 28: 637–42.
  38. Skinner M., Sanchorawala V., Seldin D.C. et al. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann. Intern. Med. 2004; 140: 85–93.
  39. Dispenzieri A., Kyle R.A., Lacy M.Q. et al. Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study. Blood 2004; 103: 3960–3.
  40. Schonland S.O. Current status of hematopoietic cell transplantation in the treatment of systemic amyloid light-chain amyloidosis. Bone Marrow Transplant. 2011 Jul 25: 1–11.
  41. Gertz M.A., Lacy M.Q., Dispenzieri A. et al. Stem cell transplantation for the management of primary systemic amyloidosis. Am. J. Med. 2002; 113: 549–55.
  42. Comenzo R.L., Gertz M.A. Autologous stem cell transplantation for primary systemic amyloidosis. Blood 2002; 99: 4276–82.
  43. Cibeira M.T., Sanchorawala V., Seldin D.C. et al. Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients. Blood 2011; 118(16): 4346–52.
  44. Sanchorawala V., Wright D.G., Quillen K. et al. Tandem cycles of high-dose melphalan and autologous stem cell transplantation increases the response rate in AL amyloidosis. Bone Marrow Transplant. 2007; 40: 557–62.
  45. Quillen K., Seldin D.C., Finn K.T., Sanchorawala V. A second course of high-dose melphalan and auto-SCT for the treatment of relapsed AL amyloidosis. Bone Marrow Transplant. 2011; 46: 976–80.
  46. Cohen A.D., Zhou P., Reich L. et al. Adjuvant dexamethasone (D) ± thalidomide (T) improves hematologic and organ responses after risk-adapted high-dose melphalan with autologous stem cell transplant (SCT) for patients with systemic AL amyloidosis (AL) [abstract]. Blood 2005; 106: 340a, abstr. 1163.
  47. Landau H., Hassoun H., Rosenzweig M.A. et al. Maintained Hematologic and Organ Responses at Two Years Following Stem Cell Transplant In Systemic Light-Chain Amyloidosis (AL) Using Short-Course Bortezomib and Dexamethasone Consolidation Therapy. ASH Annual Meeting Abstracts 2010; 116: 2391.
  48. Sanchorawala V., Wright D.G., Seldin D.C. et al. High-dose intravenous melphalan and autologous stem cell transplantation as initial therapy or following two cycles of oral chemotherapy for the treatment of AL amyloidosis: results of a prospective randomized trial. Bone Marrow Transplant. 2004; 33: 381–8.
  49. Perz J.B., Schonland S.O., Hundemer M. et al. High-dose melphalan with autologous stem cell transplantation after VAD induction chemotherapy for treatment of amyloid light chain amyloidosis: a single centre prospective phase II study. Br. J. Haematol. 2004; 127: 543–51.
  50. Schonland S.O., Lokhorst H., Buzyn A. et al. Allogeneic and syngeneic hematopoietic cell transplantation in patients with amyloid light-chain amyloidosis: a report from the European Group for Blood and Marrow Transplantation. Blood 2006; 107: 2578–84.
  51. Lewis W.D., Skinner M., Simms R.W. et al. Orthotopic liver transplantation for familial amyloidotic polyneuropathy. Clin. Transplant. 1994; 8: 107–10.
  52. Holmgren G., Ericzon B.G., Groth C.G. et al. Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis. Lancet 1993; 341: 1113–6.
  53. Gillmore J.D., Goodman H.J., Lachmann H.J. et al. Sequential heart and autologous stem cell transplantation for systemic AL amyloidosis. Blood 2006; 107: 1227–9.
  54. Isoniemi H., Kyllonen L., Ahonen J. et al. Improved outcome of renal transplantation in amyloidosis. Transpl. Int. 1994; 7(Suppl. 1): S298–300.
  55. Hrncic R., Wall J., Wolfenbarger D.A. et al. Antibody-mediated resolution of light chain-associated amyloid deposits. Am. J. Pathol. 2000; 157: 1239–46.
  56. Zhou P., Comenzo R.L. CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy. Blood 2008; 111: 3403–6.
  57. Palladini G. Dispenzieri A., Gertz M.A. et al. Validation of the criteria of response to treatment in AL amyloidosis. Blood 2010; 116: 1364a.

International prognostic score in advanced Hodgkin’s lymphoma

LYMPHOID TUMORS , , , ,

K.D. Kaplanov1, A.L. Shipaeva1, V.A. Vasil’yeva1, E.G. Gemdjian2, I.V. Matveeva1, L.S. Tregubova1, T.U. Klitochenko1, K.V. Demidenko1, O.B. Kalashnikova1, G.U. Vyskub1, O.E. Golubeva1, O.V. Levina1, V.A. Orlov1, and E.A. Demina3

1 Volgograd Regional Oncology Clinic #1, Volgograd, Russian Federation

2 Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation

3 N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

ABSTRACT

Since chemotherapy of Hodkgin’s lymphoma was introduced in early 60s, it has undergone fundamental changes that were associated with dramatic improvement in the disease prognosis. Currently, the various intensive modifications of original BEACOPP, such as BEACOPP-14 and escalate BEACOPP, are among the most widely used for treatment of advanced Hodkgin’s lymphoma.

Initially, the International Prognostic Score (IPS) was developed for patients treated with MOPP and MOPP-ABVD protocols. We suggest that due to the well-known changing value of the various prognostic signs with protocols of different intensity, the significance of IPS for BEACOPP-based therapy should be reconsidered.

One hundred seventy two patients with advanced Hodgkin’s lymphoma were included in our trial. All these patients were treated at the Hematology department of Volgograd Regional Oncology Clinic #1. Treatment options were as follows: 64 (37%), 84 (49%), and 24 (14%) patients received intensive BEACOPP-based, standard BEACOPP, or ABVD therapy, respectively. The final data presented are related to the period up to June 30, 2012.

We retrospectively evaluated the treatment outcomes for each IPS group. To distinguish the most significant prognostic signs from all six IPS factors, we studied the impact of each factor on treatment efficacy.

The greatest difference in overall 3- and 4-year survival was observed between the groups of patients with IPS 0–1 and ³ 2; for IPS 0–1, 3- and 4-year overall survival rate was 93%; for IPS ³ 2, 3- and 4-year overall survival rate was 81% and 75%, respectively (p = 0.05). 3-year overall survival was significantly negatively affected by such factors as age over 45 (70% versus 87%, relative risk (RR) = 3.95% CI: 1.7–7, p = 0.01) and albumin level < 40 g/L (79% versus 88%, RR= 2.8, 95% CI: 1.2–6.8, p = 0.02). Overall 3-year survival rate in males (n = 91) and females (n = 81) was 80% and 88%, respectively (p = 0.09). We found no effect on overall and freedom-from-treatment-failure survival (FFTF) of such factors as hemoglobin levels, lymphocyte count, leukocytes count, and IV stage disease. With respect to overall survival, multivariate analysis showed the greatest significance of age (relative risk, RR =3.6, 95% CI: 1.8–7, p = 0.001) and albumin level (OR = 2.6, 95% CI: 1.1–6, p = 0.036).

Keywords: Hodgkin’s lymphoma, international prognostic score (IPS), advanced stages, overall survival (OS), freedom-from-treatment-failure survival (FFTFS), BEACOPP, ABVD

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REFERENCES

  1. Richardson S.E., McNamara C. The management of classical Hodgkin’s lymphoma: past, present, and future. Advant. Hematol. 2011; 2011: 1–17.
  2. Kuruvilla J. Standard therapy of advanced Hodgkin lymphoma. Hematol. Am. Soc. Hematol. Educ. 2009: 497–506.
  3. Federico M., Luminari S., Iannitto E. et al. ABVD compared with BEACOPP compared with CEC for initial treatment of patients with advanced Hodgkin’s lymphoma: Results from the HD2000 Gruppo Italiani perlo Studio dei Linfomi Trial. Clin. Oncol. 2009; 27: 805–11.
  4. Gianni A.M., Rambaldi A., Zinzani P. Comparable 3-year outcome following ABVD or BEACOPP first-line chemotherapy, plus pre-planned high-dose salvage, in advanced Hodgkin lymphoma: a randomized trial of the Michelagelo, GITIL and IIL cooperative groups. ASCO meeting Chicago, 2008. Abstract 8506.
  5. Byar D.P. Identification of prognostic factors. In: Cancer clinical trials. Methods and practice. Ed. by M.E. Buyse, M.J. Staquet, R.J. Sylvester. Oxford: Oxford University Press, 1988.
  6. Hasenclever D., Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s disease. N. Engl. J. Med. 1998; 339(21): 1506–14.
  7. R. Optimal Therapy of Advanced Hodgkin Lymphoma. ASH Education book. 2011: 310–316.
  8. Diehl V., Franklin J., Pfreundschuh M. et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. Engl. J. Med. 2003; 348(24): 2386–95.
  9. Wagstaff J., Gregory W.M., Swindell R. et al. Prognostic factors for survival in stage IIIB and IV Hodgkin’s disease: a multivariate analyses comparing two specialist treatment centers. J. Cancer. 1988; 58: 487–92.
  10. Wagstaff J., Steward W., Jones M. et al. Factors affecting remission and survival in patients with advanced Hodgkin’s disease treated with MVPP. Oncol. 1986; 4: 135–47.
  11. Straus D.J., Gaynor J.J., Myers J. et al. Prognostic factors among 185 adults with newly diagnosed advanced Hodgkin’s disease treated alternating potentially noncross-resistant chemotherapy and intermediate-dose radiation therapy. Clin. Oncol. 1990; 8: 1173–86.
  12. Proctor S.J., Taylor P., Mackie M.J. et al. A numerical prognostic index for clinical use in identification of poor-risk patients with Hodgkin’s disease at diagnosis. The Scotland and Newcastle Lymphoma Group (SNLG) Therapy Working Party. Lymphoma 1992; 7 (Suppl.): 17–20.
  13. Low S.E., Horsman J.M., Walters S.J. et al. Risk-adjusted prognostic models for Hodgkin’s disease (HD) and grade II non- Hodgkin’s lymphoma (NHL II): validation on 6728 British National Lymphoma Investigation patients. J. Hematol. 2003; 120: 277–80.
  14. Gobbi P.G., Comelli M., Grignani G.E. et al. Estimate of expected survival at diagnosis in Hodgkin’s disease: a means of weighting prognostic factors and a tool for treatment choice and clinical research. A report from the International Database on Hodgkin’s Disease (IDHD). Hematologica 1994; 79: 241–55.
  15. Moccia A.A., Donaldson J., Chhanabhai M. et al. International Prognostic Score in Advanced- Stage Hodgkin’s Lymphoma: Altered Utility in the Modern Era. J. Clin. 2012; 30: 3383–8.
  16. Капланов К.Д., Шипаева А.Л., Васильева В.А. и др. Эффективность программ химиотерапии первой линии при различных стадиях лимфомы Ходжкина. Клин. онкогематол. 2012; 1: 22–9. [Kaplanov K.D., Shipayeva A.L., Vasilyeva V.A. i dr. Effektivnost programm khimioterapii pervoy linii pri razlichnykh stadiyakh limfomy Khodzhkina (Efficacy of first-line chemotherapy programs at various stages of Hodgkin’s disease). onkogematol. 2012; 1: 22–9.]

 

Immunophenotypical and cytogenetic features of tumor cells in a patient with chronic lymphocytic leukemia associated with prolonged exposure to irradiation

LYMPHOID TUMORS , , , ,

S.N. Kolyubaeva1, I.A. Sukhina1, V.Yu. Nikitin1, T.V. Isakova1, A.S. Polyakov1, S.N. Malakhova1, N.V. Il’yin2, J.N. Vinogradova2, and L.А. Myakoshina2

1 Military Medical Aсademy, Saint Petersburg, Russian Federation

2 Russian Research Centre for Radiology and Surgical Technologies, RF Ministry of Health, Saint Petersburg, Russian Federation

ABSTRACT

In this article, we describe immunoрhenotypical and cytogenetic features of tumor cells in the patient with chronic lymphocytic leukemia (CLL) and prolonged exposure to irradiation in the history. Finding of 0.67% to 0.73% of metaphases with dicentric chromosomes confirmed the effect of radiation in this patient. Chromosome banding with mitogen stimulation of peripheral lymphocytes revealed 2% of cells with 47,XY, +12 karyotype, while FISH detected the greater number of cells with trisomy 12 in interphase bone marrow cells and peripheral lymphocytes. Immunophenotyping of bone marrow cells revealed the difference from “classic” CCL, i.e. simultaneous low-positive CD22 and CD79b expression as well as CD38 expression on the surface of tumor cells.

Keywords: chronic lymphocytic leukemia, fluorescence in situ hybridization, trisomy 12, irradiation, radiation-specific damage.

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REFERENCES

  1. Новик А.А. Классификация злокачественных лимфом. СПб.: ЭЛБИ, 2000. [Novik A.A. Klassifikatsiya zlokachestvennykh limfom (Classification of malignant lymphomas). SPb.: ELBI, 2000.]
  2. O’Brien S. Diagnosis and treatment of chronic lymphocytic leukemia. In: Neoplastic Diseases of the Blood, 3rd ed. Ed. by P.H. Wiernk, S. O’Brien, M.J. Keating. New York, Edinburgh, 2001: 151–9.
  3. Austen B., Skowronska A., Baker C. et al. Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion. Clin. Oncol. 2007; 25: 5448–7.
  4. Bea S., Lopez-Guellermo A., Ribas M. et al. Genetics imbalances in progressed B-cell chronic lymphocytic leukemia and transformed large-cell lymphoma (Richter’s syndrome). J. Pathol. 2002; 161: 957–8.
  5. Del Giudice I., Rossi D., Chiaretti S. et al. NOTCH1 mutations in +12 chronic lymphocytic leukemia (CLL) conferan unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of +12 CLL. Haematologica 2012; 97(3): 437–41.
  6. Rossi D., Rasi S., Fabbri G. et al. Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood 2012; 119(2): 521–6.
  7. Chumak V.V., Romanenko A.Y, Voillegue P.G. et al. The UkrainianAmerican study of leukemia and related disorders among Chernobyl cleanup workers from Ukraine: II. Estimation of bone marrow doses. Rad. Res. 2008; 170(6): 691–7.
  8. Romanenko A.Y., Finch S.C., Hatch M. et al. The Ukrainian-American study of leukemia and related desorders among Chernobyl cleanup workers from Ukraine: III. Radiation risk. Rad. Res. 2008; 170: 711–20.
  9. Krestinina L.Y., Preston D.L. Ostroumova E.V. et al. Protracted radiation exposure and cancer mortality in the Techa river cohort. Res. 2005; 164: 602–11.
  10. Zent C.S., Kyasa M.J., Evans R., Schichman S.A. Chronic lymphocytic leukemia incidence is substantially higher than estimated from tumor registry date. Cancer 2001; 92: 1325–30.
  11. Богданов А.Н., Саржевский В.О., Колюбаева С.Н. и др. Случай острого лимфобластного лейкоза с t(9;22) и несколькими дополнитель- ными перестройками. Гематол. и трансфузиол. 2008; 53(30): 35–8. [Bogdanov A.N., Sarzhevskiy V.O., Kolyubayeva S.N. i dr. Sluchay ostrogo limfoblastnogo leykoza s t(9;22) i neskolkimi dopolnitelnymi perestroykami (Case of acute lymphoblastic leukemia with t(9;22) and several additional rearrangements). i transfuziol. 2008; 53(30): 35–8.]
  12. Аn International System for human Cytogenetic Nomenclature. Recommendations of the International Standing Committee on the Human Cytogenetic Nomenclature. by L. Shaffer, N. Tommerup. Basel: S. Karger, 2009.
  13. Zucchetto A. Surface-antigen expression profiling (SEP) in B-cell chronic lymphocytic leukemia (B-CLL): Identification of markers with prognostic relevance. Immunol. Meth. 2005; 305: 20–32.
  14. Escudier S.M., Pereira-Leahy J.M., Drach J.M. et al. Fluorescent in situ hybridization and cytogenetic studies of trisomy 12 in chronic lymphocytic leukemia. Blood 1993; 81: 2702–7.
  15. Schlette E. CD79b expression in chronic lymphocytic leukemia. Association with trisomy 12 and atypical immunophenotype E. Arch. Lab. Med. 2003; 123: 561–6.

 

Pulmonary MALT-lymphoma: case report and literature review

LYMPHOID TUMORS , ,

A.K. Morozova, N.G. Gabeeva, and E.E. Zvonkov

Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation

ABSTRACT

This article presents a rare case of pulmonary MALT-lymphoma and literature review. An elderly patient with pulmonary MALT lymphoma was successfully treated according to R-B (rituximab + bendamustine) chemotherapy program. After 6 R-B courses, sustained remission with minimal toxicity and good tolerability was achieved.

Keywords: pulmonary MALT-lymphoma, chemotherapy, bendamustine

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REFERENCES

  1. Cadranel J., Wislez M., Antoine M. et al. Primary pulmonary lymphoma. Eur. Respir. 2002; 20: 750–62.
  2. Isaacson P., Wright D.H. Malignant lymphoma of mucosa associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 1983; 52: 1410–6.
  3. Zinzani P.L., Vittorio Stefoni V., Musuraca G. et al. Fludarabine-Containing Chemotherapy as Frontline Treatment of Nongastrointestinal Mucosa-Associated Lymphoid Tissue Lymphoma. Cancer 2004; 100(10): 2190–4.
  4. Hui H., Zhi-wei L., Chun-guo J. et al. Clinical and prognostic characteristics of pulmonary mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of 23 cases in a Chinese population. Med. J. 2011; 124(7): 1026–30.
  5. Воробьев А.И. Руководство по гематологии. Т. 2. М.: Ньюдиамед, 2003: 92–100. [Vorobyev A.I. Rukovodstvo po gematologii. T. 2 (Manual of hematology, Vol. 2). M.: Nyudiamed, 2003: 92–100.]
  6. Программное лечение заболеваний системы крови. Под ред. В.Г. Сав- ченко. Т. 2. М.: Практика, 2012: 579–93. [Programmnoye lecheniye zabolevaniy sistemy krovi. Pod red. V.G. Savchenko. T. 2 (Program therapy for hematological disorders. Ed. by V.G. Savchenko. 2). M.: Praktika, 2012: 579–93.]
  7. Zvonkov E., Krasilnikova B., Magomedova A. et al. FMC/FMC-R regimens efficiency in treatment primary extragastric MALT-lymphomas. Abstract book 2007; 92(1): 444.
  8. Красильникова Б.Б., Звонков Е.Е., Кравченко С.К. и др. Первый опыт применения программ FNC и FNC-R в лечении первичной лимфоцитомы орбиты. Гематол. и трансфузиол. 2008; 6: 3–7. [Krasilnikova B.B., Zvonkov Ye.Ye., Kravchenko S.K. i dr. Pervyy opyt primeneniya programm FNC i FNC-R v lechenii pervichnoy limfotsitomy orbity (Initial experience with FNC and FNC-R programs usage in therapy for primary orbital lymphocytoma. In: Hematol. & transfuziol.). Gematol. i transfuziol. 2008; 6: 3–7.]
  9. Yoon R.G., Kim M.Y., Songb J.W. Primary Endobronchial Marginal Zone B-Cell Lymphoma of Bronchus-Associated Lymphoid Tissue: CT Findings in 7 Patients. Korean J. Radiol. 2013; 14(2): 366–74.
  10. Zucca E., Conconi A., Laszlo D. Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 Randomized Study. Clin. Oncol. 2013; 31(5): 565–72.
  11. Domingo S., Canales M., Nicolas C. et al. Bendamustine and rituximab as first line treatment for patients with MALT lymphoma. An interim report of a phase 2 trial in Spain (MALT-2008–10). 11th International Conference on Malignant Lymphoma. Lugano, 2011. Abstract 299.
  12. Cordier J.F., Chailleux E., Lauque D. Primary pulmonary lymphomas. A clinical study of 70 cases in nonimmunocompromised patients. Chest 1993; 103(1): 201–8.
  13. Imai Н., Sunaga N., Kaira K. et al. Clinicopathological Features of Patients with Bronchial-Associated Lymphoid Tissue Lymphoma. Med. 2009; 48: 301–6.
  14. Thieblemont C., Berger F., Dumontet C. et al. Mucosa-associated lymphoid tissue lymphoma is a disseminated disease in one third of 158 patients analyzed. Blood 2013; 2000(95): 802–6.
  15. Borie R., Wislez M., Thabut G. Clinical characteristics and prognostic factors of pulmonary MALT lymphoma. Respir. J. 2009; 34: 1408–16.
  16. Troch M., Streubel B., Petkov V. et al. Does MALT Lymphoma of the Lung Require Immediate Treatment? An Analysis of 11 Untreated Cases with Longterm Follow-up. Anticancer Res. 2007; 27: 3633–8.
  17. Zinzani P.L., Magagnoli M., Galieni P. et al. Nongastrointestinal LowGrade Mucosa-Associated Lymphoid Tissue Lymphoma: Analysis of 75 Patients. Clin. Oncol. 1999; 17: 1254–8.
  18. Kocaturk C.I., Seyhan E.C., Zeki M. et al. Primary pulmonary nonHodgkin’s lymphoma: ten cases with a review of the literature. Toraks. 2012; 60(3): 246–53.
  19. Zinzani P.L., Pellegrini C., Gandolfi L. et al. Extranodal marginal zone B-cell lymphoma of the lung: experience with fludarabine and mitoxantronecontaining regimens. Oncol. 2012 Dec 5. doi: 10.1002/hon.2039.
  20. Brown J.R., Friedberg J.W., Feng Y. et al. A phase 2 study of concurrent fludarabine and rituximab for the treatment of marginal zone lymphomas. J. Haematol. 2009; 145(6): 741–8.
  21. Prabhash K., Vikram G.S., Nair R. et al. Fludarabine in lymphoproliferative malignancies: a single-centre experience. Med. J. India 2008; 21(4): 171–4.
  22. Rummel M.J., Kaiser U., Balser C. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas — Final Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting Abstracts 2010; 116: 856.
  23. Rummel M.J., Niederle N., Maschmeyer G. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 noninferiority trial. Lancet, Early Online Publication, 20 February 2013. doi: 10.1016/ S0140-6736(12)61763.

Mantle cell lymphoma: program therapy for untreated patients under 65 years

LYMPHOID TUMORS , , ,

V.I. Vorobyev1, S.K. Kravchenko1, E.G. Gemdjian1, Yu. Yu. Lorie 2, A.U. Magomedova1, A.L. Melikyan1, J.K. Mangasarova1, D.S. Mar’yin1, E.I. Dubrovin1, T.N. Obukhova1, S.A. Makhinya, V.A. Zherebtsova3, M.A. Vernyuk4, N.G. Tyurina4, and V.G. Savchenko1

1 Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation

2 Moscow Oncology Clinic #3, Russian Federation

3 Central Clinical Hospital with Polyclinic, RF Presidential Executive Office, Moscow, Russian Federation

4 P.A. Hertzen Moscow Oncology Research Institute, Moscow, Russian Federation

ABSTRACT

Background: Mantle cell lymphoma (MCL) is aggressive B-cell neoplasm which is diagnosed predominantly among older men. The use of high-dose Ara-C (12 g/m2 per course), autoSCT, and rituximab at all stages of therapy is the most effective approach but it is feasible only in patients under 60–65 years. High efficacy of gemcitabine and oxaliplatin-based regimens and irinotecan in relapsed or refractory MCL justifies their use in first-line therapy.

Objective: Assessment of toxicity and efficacy of R-DA-EPOCH/R-GIDIOX- and R-DA-EPOCH/R-HD-Met-Ara-C-regimens in primary MCL patients selected for autoSCT.

Patients and Methods: Since May 2008, 41 untreated MCL pts (median age: 54 years [29–64], M/F: 73%/27%, MIPIb: 29.3% low, 36.6% intermediate, 34.1% high risk) have been enrolled. After first R-EPOCH course (W. Wilson, 2003) completed, the patients were stratified according to toxicity emerged into 2 therapeutic groups: R-DA-EPOCH/R-HD-Met-AraC or R-DA-EPOCH/R-GIDIOX. In absence of grade 4 hematological toxicity for more than 3 days, serious infectious complications, or signs of renal failure, the pts received the R-HD-Met-Ara-C (R, 375 mg/m2 on Day 0; methotrexate, 1000 mg/m2 for 24 hours, Day 1; cytarabine, 3000 mg/m2 q 12 hrs on Days 2–3) regimen. When any of the above complications was present, the pts received the R-GIDIOX (R, 375 mg/m2 on Day 0; gemcitabine, 800 mg/m2 on Days 1 and 4; oxaliplatin, 120 mg/m2 on Day 2; irinotecan, 100 mg/m2 on Day 3; dexamethasone, 10 mg/m2 IV on Days 1–5; ifosfamide, 1000 mg/m2 on Days 1–5) regimen. Then, these regimens were reversed into either R-DA-EPOCH/R-HD-Met-Ara-C or R-DA-EPOCH/R-GIDIOX. Depending on the time until the complete response was achieved, pts received 6 to 8 therapeutic courses and autoSCT (BEAM-R) with in vivo purging using rituximab. Pts with residual tumor after autoSCT underwent local irradiation. R-maintenance was performed every 3 months for 3 years. Since Nov. 2011, all pts had received intrathecal CNS prophylaxis (including the patients who had undergone autoSCT during the year preceding Nov. 2011). The protocol was approved by the local ethics committee. Pts were analyzed using the intention-to-treat model. Toxicity assessment was performed for 124 R-DA-EPOCH, 87 R-HD-Met-Ara-C, and 51 R-GIDIOX courses.

Results: The median follow-up was 22 months (range 4–60). By April 2013, 35 patients had undergone autoSCT: 21 and 14 from R-HD-Met-Ara-C- and R-GIDIOX arm, respectively. One patient died from acute renal failure and septic shock at the induction stage after first HD-Met-AraC course. R-maintenance therapy was completed in 5 patients. In all patients who had received R-HD-Met-Ara-C, CR was achieved. In the R-GIDIOX arm, OR rate was 93%: 12 CR, 2 PR, and 1 case of disease progression after 5 courses. The most common non-hematological R-GIDIOX toxicity was related to the liver with elevated aminotransferases up to Grades 1–2 and 3–4 in 64.7% and 7.8% of cases, respectively, with no clinical manifestations. The sources of stem cells was PB in 27 out of 31 patients, and in 4 cases of harvest failure after 3 R-GIDIOX and 1 HD-Met-AraC BM was used. Hematological toxicity of R-GIDIOX course included grade 4 leukopenia in 74.5% (medium duration: 5 days, range: 1–13) and grade 4 thrombocytopenia in 39.2%. The estimated 5-years OS for the R-GIDIOX and R-HD-Met-AraC groups was 93 ± 7% and 79 ± 12%, respectively. The estimated 5-years EFS for the R-GIDIOX and R-HD-Met-AraC groups was 59 ± 19% and 74 ± 12%, respectively.

Conclusions: The HD-Met-Ara-C regimen is highly toxic, and it can be used only in 2/3 of patients under 65 years. The R-GIDIOX regimen is less toxic than HD-Met-Ara-C and equally effective with regard to the response induction and mobilizing necessary amount of autologous stem cells, so it can be recommended for the patients in whom Ara-C and methotrexate in high doses carry the high risk of life-threatening consequences.

Keywords: Mantle cell lymphoma, treatment, autoSCT, maintenance therapy.

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REFERNCES

  1. Лорие Ю.Ю. Лимфома из клеток мантийной зоны: клинические формы, морфологические варианты, диагностика и лечение: Автореф. дис. … канд. мед. наук. М., 2005. [Loriye Yu.Yu. Limfoma iz kletok mantiynoy zony: klinicheskiye formy,  kand. med.¼morfologicheskiye varianty, diagnostika i lecheniye: Avtoref. dis.  nauk (Mantle cell lymphoma: clinical forms, morphological variants, diagnosis, and management. Author’s summary of dissertation for the degree of PHD). M., 2005.]
  2. Argatoff L.H., Connors J.M., Klasa R.J. et al. Mantle cell lymphoma: a clinicopathologic study of 80 cases. Blood 1997; 89: 2067–78.
  3. Yatabe Y., Suzuki R., Tobinai K. et al. Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma. Blood 2000; 95: 2253–61.
  4. Wlodarska I., Meeus P., Stul M. et al. Variant t(2;11)(p11;q13) associated with the IgK-CCND1 rearrangement is a recurrent translocation in leukemic small-cell B-non-Hodgkin lymphoma. Leukemia 2004; 18: 1705–10.
  5. Komatsu H., Iida S., Yamamoto K. et al. A variant chromosome translocation at 11q13 identifying PRAD1/Cyclin Dl as the BCL-1 Gene. Blood 1994; 84: 1226–31.
  6. Vose J.M. Mantle cell lymphoma: 2012 update on diagnosis, risk-stratification, and clinical management. J. Hematol. 2012; 87(6): 604–9.
  7. Vegliante M.C., Palomero J., Perez-Galen P. et al. SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma. Blood 2013; 121(12): 2175–85.
  8. Mozos A., Royo A., Hartmann E. et al. SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype. Haematologica 2009; 94(11): 1555–62.
  9. Fernandez V., Salamero O., Espinet B. et al. Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res. 2010; 70(4): 1408–18.
  10. Zhou Y., Wang H., Fang W. et al. Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer 2008; 113: 791–8.
  11. Howard O.M., Gribben J.G., Neuberg D.S. et al. Rituximab and CHOP induction therapy for newly diagnosed mantle cell lymphoma: molecular complete responses are not predictive of progression-free survival. Clin. Oncol. 2002; 20: 1288–94.
  12. Lenz G., Dreyling M., Hoster E. et al. Immunochemotherapy With Rituximab and Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Significantly Improves Response and Time to Treatment Failure, But Not Long-Term Outcome in Patients With Previously Untreated Mantle Cell Lymphoma: Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG). Clin. Oncol. 2005; 23: 1984–92.
  13. Romaguera J., Fayad L., Feng L. et al. Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximabhigh dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma. J. Haematol. 2010; 150(2): 200–8.
  14. Geisler C.H., Kolstad A., Laurell A. et al. Nordic MCL2 trial update: sixyear follow-up after intensive immunochemotherapy for untreated mantle celllymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur. J. Haematol. 2012; 158(3): 355–62.
  15. Hermine O., Hoster E., Walewski J. et al. Alternating Courses of 3x CHOP and 3x DHAP Plus Rituximab Followed by a High Dose ARA-C Containing Myeloablative Regimen and Autologous Stem Cell Transplantation (ASCT) Is Superior to 6 Courses CHOP Plus Rituximab Followed by Myeloablative Radiochemotherapy and ASCT In Mantle Cell Lymphoma: Results of the MCL Younger Trial of the European Mantle Cell Lymphoma Network (MCL net). Blood 2010; 116: Abstract 110.
  16. Pott C., Hoster E., Beldjord K. et al. R-CHOP/R-DHAP Compared to RCHOP Induction Followed by High Dose Therapy with Autologous Stem Cell Transplantation Induces Higher Rates of Molecular Remission In MCL: Results of the MCL Younger Intergroup Trial of the European MCL Network. Blood 2010; 116: Abstract 965.
  17. Tam C., Bassett R., Ledesma C. et al. Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell Lymphoma. Blood 2009; 113(1): 8.
  18. Bernstein S.H., Epner E., Unger J.M. et al. A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Oncol. 2013 Mar 15.
  19. Delarue R., Haioun C., Ribrag V. et al. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d’Etude des Lymphomes de l’Adulte. Blood 2013; 121(1): 48–53.
  20. Hoster E., Dreyling M., Klapper W. et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 2008; 111: 558–65.
  21. Tiemann M., Schrader C., Klapper W. et al. Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network. J. Haematol. 2005; 131: 29–38.
  22. Geisler C., Kolstad A., Laurell A. et al. The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT). Blood 2010; 115: 1530–3.
  23. Geisler C. Front-line therapy of MCL. Hematologica 2010; 95: 1241–3.
  24. Damon L.E., Johnson J.L., Niedzwiecki D. et al. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. Clin. Oncol. 2009; 27(36): 6101–8.
  25. Fayad L., Thomas D., Romaguera J. Update of the M. D. Anderson Cancer Center experience with hyper-CVAD and rituximab for the treatment of mantle cell and Burkitt-type lymphomas. Lymph. Myeloma 2007; 8(Suppl. 2): S57–62.
  26. Vigouroux S., Gaillard F., Moreau P. et al. High-dose therapy with autologous stem cell transplantation in first response in mantle cell lymphoma. Haematologica 2005; 90(11): 1580–2.
  27. Rodriguez J., Gutierrez A., Palacios A. et al. Rituximab, gemcitabine and oxaliplatin: An effective regimen in patients with refractory and relapsing mantle cell lymphoma. Lymphoma 2007; 48: 2172–8.
  28. Corazzelli G., Capobianco G., Arcamone M. et al. Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. Cancer Chemother. Pharmacol. 2009; 64: 907–16.
  29. Corazzelli G., Russo F., Capobianco G. et al. Gemcitabine, ifosfamide, oxaliplatin and rituximab (R-GIFOX), a new effective cytoreductive/mobilizing salvage regimen for relapsed and refractory aggressive non-Hodgkin’s lymphoma: results of a pilot study. Oncol. 2006; 17(Suppl. 4): iv18–24.
  30. Park B.B., Kim W.S., Eom H.S. et al. Salvage therapy with gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for B-cell non-Hodgkin’s lymphoma: a consortium for improving survival of lymphoma (CISL) trial. New Drugs 2011; 29: 154–60.
  31. Suzumiya J., Suzushima H., Maeda K. et al. Phase I study of the combination of irinotecan hydrochloride, carboplatin, and dexamethasone for the treatment of relapsed or refractory malignant lymphoma. J. Hematol. 2004; 79(3): 266–70.
  32. Hara S., Yokote T., Akioka T. et al. Successful treatment of refractory mantle cell lymphoma with irinotecan. Rinsho Ketsueki. 2005; 46(5): 358–62.
  33. Wilson W., Dunleavy K., Pittaluga S. et al. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. Clin. Oncol. 2008; 26: 2717–24.
  34. Cheson B., Pfistner B., Juweid M. et al. Revised response criteria for malignant lymphoma. Clin. Oncol. 2007; 25: 579–86.