Hodgkin’s lymphoma

The Use of Brentuximab Vedotin in Relapsed/Refractory Hodgkin’s Lymphoma in the Kransnodar Region

NOVEL DRUGS , , ,

OD Serdyuk, DA Yaskul’skii

Clinical Oncology Dispensary No. 1 of the Krasnodar region, 146 Dimitrova str., Krasnodar, Russian Federation, 350040

For correspondence: Ol’ga Dmitrievna Serdyuk, 146 Dimitrova str., Krasnodar, Russian Federation, 350040; Tel.: +7(918)441-08-33; e-mail: 7-18@mail.ru

For citation: Serdyuk OD, Yaskul’skii DA. The Use of Brentuximab Vedotin in Relapsed/Refractory Hodgkin’s Lymphoma in the Kransnodar Region. Clinical oncohematology. 2018;11(1):50-3.

DOI: 10.21320/2500-2139-2018-11-1-50-53

ABSTRACT

The treatment of relapsed/refractory Hodgkin’s lymphoma (HL) remains to be a challenging issue. The morbidity of HL is reported to increase in the Krasnodar region. While considerable progress in the treatment of HL has been achieved, the relapse rate still remains high. The standard second-line treatment allows for the disease control in only half of cases of relapsed HL. Until recently, however, relapses after autologous hematopoietic stem cell transplantation (autoHSCT) could be treated only by polychemotherapy aimed at slowing the tumor growth. The use of anti-CD30 conjugated monoclonal antibodies and cytotoxic agent was shown to control the relapsed disease after high dose chemotherapy followed by autoHSCT. The present study provides pharmacological characteristics of brentuximab vedotin, its antineoplastic mechanism as well as the author’s own clinical experience in the management of a female patient with HL after autoHSCT.

Keywords: Hodgkin’s lymphoma, brentuximab vedotin, targeted therapy, relapse.

Received: November 25, 2017

Accepted: January 8, 2018

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REFERENCES

  1. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. М.: Буки Веди, 2016. С. 9, 22. [Poddubnaya IV, Savchenko VG, eds. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. (Russian clinical guidelines in diagnosis and treatment of lymphoproliferative disorders.) Moscow: Buki Vedi Publ.; 2016. pp. 9, 22. (In Russ)]
  2. Злокачественные новообразования в России в 2013 г. (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Стравинского, Г.В. Петровой. М., 2017. С. 113, 212. [Kaprina AD, Stravinskii VV, Petrova GV, eds. Zlokachestvennye novoobrazovaniya v Rossii v 2013 godu (zabolevaemost’ i smertnost’). (Malignant Tumors in Russia 2013 (Morbidity and Mortality.) Moscow; 2015. pp. 113, 212. (In Russ)]
  3. Казанцева М.В., Тесленко Л.Г., Бондарева И.С. и др. Злокачественные новообразования в Краснодарском крае (2010–2014 годы). Состояние онкологической помощи населению. Краснодар, 2015. С. 262. [Kazantseva MV, Teslenko LG, Bondareva IS, et al. Zlokachestvennye novoobrazovaniya v Krasnodarskom krae (2010–2014 gody). Sostoyanie onkologicheskoi pomoshchi naseleniyu. (Malignant tumors in the Krasnodar region (2010–2014). The state of cancer care.) Krasnodar; 2015. pp. 262. (In Russ)]
  4. Ferrero S, Drandi D, Mantoan B, et al. Minimal residual disease detection in lymphoma and multiple myeloma: impact on therapeutic paradigms. Hematol Oncol. 2011;29(4):167–76. doi: 10.1002/hon.989.
  5. Демина Е.А. Брентуксимаб ведотин: новые возможности лечения рецидивов и рефрактерных форм лимфомы Ходжкина. Клиническая онкогематология. 2016;9(4):398–405. doi: 10.21320/2500-2139-2016-9-4-398-405. [Demina EA. Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas. Clinical oncohematology. 2016;9(4):398–405. doi: 10.21320/2500-2139-2016-9-4-398-405. (In Russ)]
  6. Katz J, Janik JA, Yones A. Brentuximab vedotin (SGN-35). Clin Cancer Res. 2011;17(20):6428–36. doi: 10.1158/1078-0432.CCR-11-0488.
  7. Chen R, Gopal AK, Smith SE, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016;128(12):1562–6. doi: 10.1182/blood-2016-02-699850.
  8. Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30(18):2183–9. doi: 10.1200/jco.2011.38.0410.
  9. Gopal AK, Chen R, Smith SE, et al. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015;125(8):1236–43. doi: 10.1182/blood-2014-08-595801.

Classification of Conditioning Regimens for Bone Marrow Transplantation: Historical Background and Current Perspectives

BONE MARROW TRANSPLANTATION , , , , , ,

KN Melkova, GD Petrova, NV Gorbunova, TZ Chernyavskaya, OP Trofimova

NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Kapitolina Nikolaevna Melkova, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: frolov63@bk.ru

For citation: Melkova KN, Petrova GD, Gorbunova NV, et al. Classification of Conditioning Regimens for Bone Marrow Transplantation: Historical Background and Current Perspectives. Clinical oncohematology. 2017;10(4):494–500 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-494-500

ABSTRACT

Hematopoietic stem cells transplantation is a current standard treatment for many oncohematological diseases. The milestone of any type of transplantation is the choice of conditioning regimen. This article presents the principles of classification of conditioning regimens in terms of myeloablativity and discusses the concepts of “autologous transplantation”, “high-dose chemotherapy supported by hematopoietic stem cells”, “allogeneic transplantation” and “immunotherapy”. Up-to-date uniform classification of conditioning regimens may serve an important prognostic component in assessing both the risks and efficacy of hematopoietic stem cells transplantation.

Keywords: conditioning regimens, allogeneic hematopoietic stem cell transplantation, autologous hematopoietic stem cell transplantation, total therapeutic exposure, acute leukemia, Hodgkin’s lymphoma, multiple myeloma.

Received: March 29, 2017

Accepted: July 8, 2017

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REFERENCES

  1. Passweg JR, Baldomero H, Bader P, et al. Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants. Bone Marrow Transplant. 2015;50(4):476–82. doi: 10.1038/bmt.2014.312.
  2. Мелкова К.Н., Абдусаламов С.Н., Горбунова Н.В. и др. Трансплантация костного мозга при острых лейкозах. Клиническая онкогематология. 2010;3(4):395–9.[Melkova KN, Abdusalamov SN, Gorbunova NV, et al. Bone Marrow Transplantation in Case of Acute Leukemia. Klinicheskaya onkogematologiya. 2010;3(4):395–9. (In Russ)]
  3. Петрова Г.Д., Мелкова К.Н., Чернявская Т.З. и др. Петрова Г.Д., Мелкова К.Н., Чернявская Т.З. и др. Аутологичная трансплантация гемопоэтических стволовых клеток при первично-рефрактерном течении лимфомы Ходжкина: мнимый цугцванг или промежуточный ход? Клиническая онкогематология. 2015;8(3):321–30. doi: 10.21320/2500-2139-2015-8-3-321-330.[Petrova GD, Melkova KN, Chernyavskaya TZ, et al. Autologous Stem Cell Transplantation in Primary Refractory Hodgkin’s Lymphoma: Supposed Zugzwang or Zwischenzug? Clinical oncohematology. 2015;8(3):321–30. doi: 10.21320/2500-2139-2015-8-3-321-330. (In Russ)]
  4. Петрова Г.Д., Мелкова К.Н., Чернявская Т.З. и др. Первично-рефрактерное течение лимфомы Ходжкина и аутологичная трансплантация гемопоэтических стволовых клеток. Результаты одноцентрового проспективного исследования. Российский онкологический журнал. 2015;20(3):4–11.[Petrova GD, Melkova KN, Chernyavskaya TZ, et al. Primary-Refractory Course of Hodgkin’s Lymphoma and Autologous Hematopoietic Stem Cell Transplantation. Results of Single Center Prospective Study. Rossiiskii onkologicheskii zhurnal. 2015;20(3):4–11. (In Russ)]
  5. Петрова Г.Д., Мелкова К.Н., Горбунова Н.В. и др. Аутологичная трансплантация гемопоэтических стволовых клеток для консолидации ремиссии острого миелобластного лейкоза с факторами неблагоприятного прогноза в дебюте заболевания. Онкогематология. 2016;11(1):52–61. doi: 10.17650/1818-8346-2016-11-1-52-61.[Petrova GD, Melkova KN, Gorbunova NV, et al. Autologous Hematopoietic Stem Cell Transplantation for Remission Consolidation of Acute Myeloblastic Leukemia with Factors of Poor Prognosis in Disease Onset. Oncohematology. 2016;11(1):52–61. doi: 10.17650/1818-8346-2016-11-1-52-61. (In Russ)]
  6. Мелкова К.Н., Петрова Г.Д., Чернявская Т.З. Заготовка гемопоэтических стволовых клеток для проведения аутологичной трансплантации у пациентов с лимфомой Ходжкина неблагоприятного прогноза. Вестник ФГБНУ «РОНЦ им. Н.Н. Блохина». 2015;26(3):51–6.[Melkova KN, Petrova GD, Chernyavskaya TZ. Hematopoietic Stem Cells Preparation for Autologous Transplantation in Patients with Hodgkin’s Lymphoma of Poor Prognosis. Vestnik FGBNU «RONTs im. N.N. Blokhina». 2015;26(3):51–6. (In Russ)]
  7. Чернявская Т.З., Мелкова К.Н., Горбунова Н.В. и др. Использование стимулированного костного мозга для трансплантации в онкологии. Онкология. 2012;(2, приложение):28–33.[Chernyavskaya TZ, Melkova KN, Gorbunova NV, et al. Usage of Stimulated Bone Marrow for Oncology Transplantation. Onkologiya. 2012;(2 Suppl):28–33. (In Russ)]
  8. Melkova K, Chernyavskaya T, Abdusalamov S, et al. Application of autologous stimulated bone marrow as a source of hematopoietic material for transplantation. Cell Ther Transplant. 2011;3(12):33.
  9. Melkova K, Chernyavskaya T, Abdusalamov S, et al. Using stimulated bone marrow as a source of hematopoietic stem cells for allogenic transplantation. Cell Ther Transplant. 2011;3(12):34.
  10. Мелкова К.Н., Абдусаламов С.Н., Горбунова Н.В. и др. Интенсивная сопроводительная терапия в онкологии и гематологии. Вестник московского онкологического общества. 2011;2:3–4.[Melkova KN, Abdusalamov SN, Gorbunova NV, et al. Intensive Supportive Therapy in Oncology and Hematology. Vestnik moskovskogo onkologicheskogo obshchestva. 2011;2:3–4. (In Russ)]
  11. Мелкова К.Н., Абдусаламов С.Н., Горбунова Н.В. и др. Интенсивная сопроводительная терапия в гематологии. Клиническая онкогематология. 2011;4(1):70–4.[Melkova KN, Abdusalamov SN, Gorbunova NV, et al. Intensive Supportive Therapy in Hematology. Klinicheskaya onkogematologiya. 2011;4(1):70–4. (In Russ)]
  12. Мелкова К.Н. Аллогенная трансплантация костного мозга. Клиническая онкогематология. 2012;5(1):1–12.[Melkova KN. Allogeneic Bone Marrow Transplantation. Klinicheskaya onkogematologiya. 2012;5(1):1–12. (In Russ)]
  13. Vriesendorp HM. Aims of the conditioning. Exp Hematol. 2003;31(10):844–54. doi: 10.1016/s0301-472x(03)00229-7.
  14. Bacigalupo A, Sormani MP, Lamparelli T, et al. Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation. Haematologica. 2004;89(10):1238–47.
  15. Мелкова К.Н., Горбунова Н.В., Чернявская Т.З. и др. Тотальное облучение организма человека при трансплантации костного мозга. Клиническая онкогематология. 2012;5(2):96–114.[Melkova KN, Gorbunova NV, Chernyavskaya TZ, et al. Total Human Body Irradiation at Bone Marrow Transplantation. Klinicheskaya onkogematologiya. 2012;5(2):96–114. (In Russ)]
  16.  Gratwohl A, Carreras E. Principles of conditioning. In: Apperley J, Carreras E, Gluckman E, Masszi T, eds. Hematopoietic Stem Cell Transplantation, 6th edition. Genoa: Forum service editore; 2012. pp. 122–37.
  17. Bensinger WI. High-dose preparatory regimens. In: Forman SJ, Negrin RS, Antin JH, eds. Thomas’ Hematopoietic Cell Transplantation, 5th edition. Willey Blackwell; 2016. Vol. 1. pp. 223–31.
  18. Лебеденко И.М., Ратнер Т.Г., Водяник В.В. и др. Проведение тотального облучения пациента перед трансплантацией костного мозга. Радиационная онкология и ядерная медицина. 2012;2:30–6.[Lebedenko IM, Ratner TG, Vodyanik VV, et al. Performance of Total Patient Irradiation before Bone Marrow Transplantation. Radiatsionnaya onkologiya i yadernaya meditsina. 2012;2:30–6. (In Russ)]
  19. Лебеденко И.М., Ратнер Т.Г., Водяник В.В. и др. Техническое и дозиметрическое обеспечение тотального облучения пациента перед трансплантацией костного мозга. Медицинская физика. 2012;3(55):11–9.[Lebedenko IM, Ratner TG, Vodyanik VV, et al. Technical and Radiation-Monitoring Supply of Total Patient Irradiation before Bone Marrow Transplantation. Meditsinskaya fizika. 2012;3(5):11–9. (In Russ)]
  20. Лебеденко И.М., Чернявская Т.З., Ставицкий Р.В. и др. Технический контроль состояния организма и его систем в процессе химио-лучевой терапии и трансплантации костного мозга при острых лейкозах. Медицинская техника. 2014;5:32–7.[Lebedenko IM, Chernyavskaya TZ, Stavitskii RV, et al. Technical Control of Patient’s Body State and Its Systems in Process of Chemoradiotherapy and Bone Marrow Transplantation. Meditsinskaya tekhnika. 2014;5:32–7. (In Russ)]
  21. Storb RF, Champlin R, Riddell SR, et al. Non-myeloablative transplants for malignant disease. Hematology Am Soc Hematol Educ Program. 2001;1:375–91. doi: 10.1182/asheducation-2001.1.375.
  22. Мелкова К.Н., Петрова Г.Д. Материалы 41-го конгресса Европейского общества по трансплантации костного мозга. Клиническая онкогематология. 2015;8(3):343–52.[Melkova KN, Petrova GD. Materials of 41st Congress of European Society of Bone Marrow Transplantation. Clinical oncohematology. 2015;8(3):343–52. (In Russ)]
  23. Sorror ML, Maris MB, Storer B, et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood. 2004;104(4):961–8. doi: 10.1182/blood-2004-02-0545.
  24. Giralt S, Ballen K, Rizzo D, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15(3):367. doi: 10.1016/j.bbmt.2008.12.497.
  25. Khouri I, Giralt S, Champlin R. Non-Myeloablative Allogeneic Hematopoietic Transplantation and Induction of Graft-Versus-Malignancy. In: Bashey A, Ball ED, eds. Cancer Treatment and Research. Boston: Springer; 2002. рр. 137–47. doi: 10.1007/978-1-4615-0919-6_7.

First-Line Therapy for Patients with Advanced Hodgkin’s Lymphoma: Efficacy and Toxicity of Intensive ЕАСОРР-14 Program (NN Blokhin National Medical Cancer Research Center Data)

LYMPHOID TUMORS , ,

EA Demina1, AA Leont’eva1, GS Tumyan1, YuE Ryabukhina1, OP Trofimova1, NV Volkova1, YuI Pryamikova1, VM Sotnikov2, VB Larionova1, EG Medvedovskaya1, EV Paramonova1, LV Manzyuk1, NA Probatova1, NV Kokosadze1, EA Osmanov1

1NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2Russian Scientific Center of Radiology and Nuclear Medicine, 86 Profsoyuznaya str., Moscow, Russian Federation, 117997

For correspondence: Prof. Elena Andreevna Demina, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-90-89; e-mail: drdemina@yandex.ru

For citation: Demina EA, Leont’eva AA, Tumyan GS, et al. First-Line Therapy for Patients with Advanced Hodgkin’s Lymphoma: Efficacy and Toxicity of Intensive ЕАСОРР-14 Program (NN Blokhin National Medical Cancer Research Center Data). Clinical oncohematology. 2017;10(4):443–52 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-443-452

ABSTRACT

Aim. To assess the efficacy and toxicity of intensive 6 courses EACOPP-14 treatment with or without radiotherapy (RT) for advanced stages of Hodgkin’s lymphoma (HL).

Materials & Methods. From November 2009 to February 2015, 95 patients with advanced stages of HL (IIX–IIE, III–IV) aged between 17 and 50 years (median 29 years) were selected for the participation in the protocol ЛХМосква1-3. The study population consisted of 46.3 % men and 53.7 % women. The results of the treatment were assessed in 91 patients who have received more than 2 courses of EACOPP-14. The follow up period was at least 3 months after the receiving the therapy. Consolidation RT with a total dose of 30 Gy for residual tumor lesions and/or initially large tumors was performed after the chemotherapy.

Results. Complete remission was achieved in 82 (90.1 %) patients, partial remission in 2 (2.2 %), and the progression was observed in 7 (7.7 %) patients. The overall 4-year survival rate was 90.8 %, the progression-free survival was 88.2 %. The toxicity of the ЕАСОРР-14 program was slightly lower than that of 8 courses of ВЕАСОРРesc, and was comparable to the toxicity of other modifications of intensified ВЕАСОРР scheme. Hematological toxicity grade 3 and 4 was most commonly observed: leukopenia was observed after 64.9 % of courses, anemia — after 24 % of courses, thrombocytopenia — after 3.8 % of courses. The rate of infections did not singificantly differ and accounted for 24 %. The most frequent non-infectious complications were mucositis (21.1 %) and polyneuropathy (11.7 %). Complications resulted in the change of treatment in only 3 (3.01 %) of patients. The exclusion of bleomycine from the ЕАСОРР-14 program reduced the frequency of RT complications. Grade 3 pulmonitis developed in 4.5 % of cases, while radiation-induce pulmonary fibrosis verified by CT developed in 15.2 % of cases. The ЕАСОРР-14 6 courses program showed its high efficacy both with and without RT, high tolerance and the possibility of full administration for the majority of patients with the various stages of HL.

Conclusion. Current research showed the efficacy of treatment without RT for patients with advanced stages of HL with negative PET results and small (< 2.5 cm) residual tumors after intensive ЕАСОРР-14 program. This approach allowed to avoid a number of late treatment complications.

Keywords: Hodgkin’s lymphoma, advanced stages, intensive first-line chemotherapy.

Received: March 10, 2017

Accepted: June 23, 2017

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REFERENCES

  1. Hodgkin lymphoma. In: Engert A, Jounes A, eds. Hematologic malignancies, 2nd edition. Berlin, Heidelberg: Springer; 2015. pp. 3–437. doi: 10.1007/978-3-319-12505-3.
  2. Демина Е.А. Современная терапия первичных больных лимфомой Ходжкина: Автореф. дис. … д-ра мед. наук. М., 2006.[Demina EA. Sovremennaya terapiya pervichnykh bol’nykh limfomoi Khodzhkina. (Contemporary therapy of primary patients with Hodgkin’s lymphoma.) [dissertation] Moscow; 2006. (In Russ)]
  3. Diehl V, Franklin J, Pfreundschuh M, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med. 2003;348(24):2386–95. doi: 10.1056/nejmoa022473.
  4. Engert A, Diehl V, Franklin J, et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin’s lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009;27(27):4548–54. doi: 10.1200/jco.2008.19.8820.
  5. Von Treschkow B, Kreissl S, Haverkamp H, et al. BEACOPP-escalated followed by radiotherapy of initial bulk or residual disease in advanced-stage Hodgkin lymphoma: long term follow-up of the GHSG HD9 and HD12 trials. Haematologica. 2016;101(Suppl 5): Abstract T001.
  6. Hoppe RT. Hodgkin’s disease: Second cancer after treatment Hodgkin’s disease: Complications of therapy and excess mortality. Ann Oncol. 1997;8(1):S115–8. doi: 10.1093/annonc/8.suppl_1.s115.
  7. Шахтарина С.В., Даниленко А.А., Павлов В.В. Злокачественные новообразования у больных лимфомой Ходжкина после лучевой терапии по радикальной программе и комбинированной химиолучевой терапии. Клиническая онкогематология. 2008;3(1):246–51.[Shakhtarina SV, Danilenko AA, Pavlov VV. Malignant neoplasms in patients with Hodgkin’s lymphoma after radiotherapy on radical program and combined chemoradiotherapy. Klinicheskaya onkogematologiya. 2008;3(1):246–51. (In Russ)]
  8. Ильин Н.В., Виноградова Ю.Н. Поздние осложнения терапии больных лимфомой Ходжкина. Практическая онкология. 2007;8(2):96–101.[Il’in NV, Vinogradova YuN. Late complications of therapy of patients with Hodgkin’s lymphoma. Prakticheskaya onkologiya. 2007;8(2):96–101. (In Russ)]
  9. Skoetz N, Trelle S, Rancea M, et al. Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin’s lymphoma: a systematic review and network meta-analysis. Lancet Oncol. 2013;14(10):943–52. doi: 10.1016/s1470-2045(13)70341-3.
  10. Diehl V, Haverkamp H, Peter R, et al. Eight Cycles of BEACOPP Escalated Compared with 4 Cycles of BEACOPP Escalated Followed by 4 Cycles of BEACOPP Baseline with or without Radiotherapy in Patients in Advanced Stage Hodgkin Lymphoma (HL): Final Analysis of the Randomised HD12 Trial of the German Hodgkin Study Group (GHSG). Blood. 2008;112: Abstract 1558.
  11. Sieber M, Bredenfeld H, Josting A, et al. 14-Day Variant of the Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Regimen in Advanced-Stage Hodgkin’s Lymphoma: Results of a Pilot Study of the German Hodgkin’s Lymphoma Study Group. J Clin Oncol. 2003;21(9):1734–9. doi: 10.1200/jco.2003.06.028.
  12. Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012;379(9828):1791–9. doi: 10.1016/s0140-6736(11)61940-5.
  13. Даниленко А.А., Шахтарина С.В., Афанасова Н.В. и др. Изменения в легких у больных лимфомой Ходжкина после химиотерапии по схемам СОРР, ABVD, ВЕАСОРР и облучения средостения в суммарной очаговой дозе 20–30 Гр. Клиническая онкогематология. 2010;3(4):354–8.[Danilenko AA, Shakhtarina SV, Afanasova NV, et al. Changes in lungs in patients with Hodgkin’s lymphoma after СОРР, ABVD, ВЕАСОРР chemotherapies and mediastinal exposure in overall basic dose of 20–30 Gy. Klinicheskaya onkogematologiya. 2010;3(4):354–8. (In Russ)]
  14. Martin WG, Ristow KM, Habermann TM, et al. Bleomycin Pulmonary Toxicity Has a Negative Impact on the Outcome of Patients With Hodgkin’s Lymphoma. J Clin Oncol. 2005;23(30):7614–20. doi: 10.1200/JCO.2005.02.7243.
  15. Behringer K, Goergen H, Hitz F, et al. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015;385(9976):1418–27. doi: 10.1016/S0140-6736(14)61469-0.
  16. Boll B, Goergen H, Behringer K, et al. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016;127(18):2189–92. doi: 10.1182/blood-2015-11-681064.
  17. Johnson PW, Frederico M, Fossa A, et al. Response-adapted therapy based on interim FDG-PET scans in advanced Hodgkin Lymphoma: first analysis of the safety of deescalation and efficacy of escalation in the international RATHL study (CRUK/07/033) [ICML abstract 008]. Hematol Oncol. 2015;33(Suppl 1):102.
  18. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. J Clin Oncol. 2014;32(27):3059–67. doi: 10.1200/jco.2013.54.8800.
  19. Carde P, Mounier N. ABVD (8 cycles) versus BEACOPP (4 escalated cycles => 4 baseline) in stage III-IV high-risk Hodgkin lymphoma (HL): First results of EORTC 20012 Intergroup randomized phase III clinical trial. ASCO Meeting Abstracts. 2012;30: Abstract 8002.
  20. Mounier N, Brice P, Bologna S, et al. ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): final results in stage III–IV low-risk Hodgkin lymphoma (IPS 0–2) of the LYSA H34 randomized trial. Ann Oncol. 2014;25(8):1622–8. doi: 10.1093/annonc/mdu189.
  21. Viviani S, Zinzani PL, Rambaldi A, et al. ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med. 2011;365(3):203–12. doi: 10.1056/nejmoa1100340.
  22. 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. doi: 10.1056/NEJM199811193392104.
  23. Engert A, Josting A, Haverkamp H, et al. Epoetin alfa in patients with advanced-stage Hodgkin’s lymphoma: results of the randomized placebo-controlled GHSG HD15EPO trial. J Clin Oncol. 2010;28(13):2239–45. doi: 10.1200/jco.2009.25.1835.
  24. Behringer K, Wildt L, Mueller H, et al. No protection of the ovarian follicle pool with the use of GnRH-analogues or oral contraceptives in young women treated with escalated BEACOPP for advanced-stage Hodgkin lymphoma. Final results of a phase II trial from the German Hodgkin Study Group. Ann Oncol. 2010;21(10):2052–60. doi: 10.1093/annonc/mdq066.
  25. Behringer K, Thielen I, Mueller H, et al. Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial. Ann Oncol. 2012;23(7):1818–25. doi: 10.1093/annonc/mdr575.
  26. Ларина Ю.В., Миненко С.В., Биячуев Э.Р. и др. Лечение распространенных форм лимфомы Ходжкина у подростков и молодых взрослых. Проблема эффективности и токсичности. Онкогематология. 2014;1:11–8.[Larina YuV, Minenko SV, Biyachuev ER, et al. Advanced Hodgkin’s lymphoma treatment in teenagers and young adults. Efficiency and toxicity. Onkogematologiya. 2014;1:11–8. (In Russ)]
  27. Brice P, Tredaniel J, Monsuez JJ, et al. Cardiopulmonary toxicity after three courses of ABVD and mediastinal irradiation in favorable Hodgkin’s disease. Ann Oncol. 1991;2(2):73–6. doi: 10.1093/annonc/2.suppl_2.73.
  28. Cosset JM, Hoppe RT. Pulmonary late effects after treatment of Hodgkin’s disease. In: PM Mauch, JO Armitage, et al., eds. Hodgkin’s Disease. Philadelphia: Lippincott Williams & Wilkins; 1999. 633 p.
  29. Koh ES, Sun A, Tran TH, et al. Clinical dose-volume histogram analysis in predicting radiation pneumonitis in Hodgkin’s lymphoma. Int J Radiat Oncol Biol Phys. 2006;66(1):223–8. doi: 10.1016/j.ijrobp.2006.03.063.
  30. Рябухина Ю.Е., Демина Е.А., Ларионова В.Б. Проблема инфекционных осложнений у больных лимфомой Ходжкина неблагоприятной прогностической группы. Вестник РОНЦ им. Н.Н. Блохина РАМН. 2008;19(2):50–63.[Ryabukhina YuE, Demina EA, Larionova VB. Problem of infectious complications in patients with Hodgkin’s lymphoma of poor prognostic group. Vestnik RONTs im. N.N. Blokhina RAMN. 2008;19(2):50–63. (In Russ)]

The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity

LYMPHOID TUMORS , , ,

KD Kaplanov1,2,3, TYu Klitochenko1,3, AL Shipaeva1, MN Shirokova1, IV Matveeva1, NB Lavrishina1

1 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

2 Volgograd Medical Research Center, 1 Pavshikh Bortsov pl., Volgograd, Russian Federation, 400131

3 Volgograd State Medical University, 1 Pavshikh Bortsov pl., Volgograd, Russian Federation, 400131

For correspondence: Kamil’ Daniyalovich Kaplanov, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail: kamilos@mail.ru

For citation: Kaplanov KD, Klitochenko TYu, Shipaeva АL, et al. The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity. Clinical oncohematology. 2017;10(3):358–65 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-358-365

ABSTRACT

Background. Among the newly diagnosed patients with Hodgkin’s lymphoma (HL), the proportion of elderly patients account for 15–35 %. In > 60 age group the choice of antitumor treatment requires an more individualised approach compared to a younger population. The ABVD regimen is acceptable in terms of efficiency and hematological toxicity, but is associated with a high risk of bleomycine-induced pulmonary complications. In ≥ 60 age group the morbitity and mortality of pulmonary complications account for 24 % and 18 %, respectively.

Aim. We aimed to evaluate the efficacy of the IVDG regimen in comparison with ABVD by the principle of “non-inferiority”.

Materials & Methods. This single centre, prospective, controlled, randomised study was started in 2009. The study included all primary patients aged ≥ 60 years with verified HL, regardless of the number and severity of comorbidities. The ABVD regimen was administered in 17 patients, and 20 patients received IVDG. The median age in the ABVD and IVDG groups was 67 and 70 years, respectively. The advanced stages of HL were reported in 13 (65 %) patients on IVDG, and in 12 (71 %) patients on ABVD (p = 0.9). Both of the groups were comparable in terms of the prevalence of chronic heart failure and chronic obstructive pulmonary disease. The prevalence of ischemic heart disease was higher in the IVDG group (n = 16) compared to ABVD (n = 8) (p = 0.04).

Results. IVDG and ABVD groups did not differ in the frequency of complete (14 and 10) and partial (3 and 4) remissions. Differences in 5-year overall survival were insignificant: 49 % in the IVDG group, vs 22 % in ABVD group (p = 0.41). No infectious or hemorrhagic complications were observed in both groups. The incidence of drug-induced pulmonary fibrosis after treatment was significantly lower in the IVDG group (n = 0) vs ABVD group (n = 4; 24 %) (p = 0.004).

Conclusion. The IVDG regimen may be used as first line treatment for HL in the elderly patients, especially in those having cardiac or pulmonary comorbidities. Compared to ABVD the IVDG regimen had similar efficacy and more beneficial safety profile in terms of cardiovascular and pulmonary toxicity.

Keywords: Hodgkin’s lymphoma, elderly patients, comorbidity, chemotherapy.

Received: December 22, 2016

Accepted: March 5, 2017

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REFERENCES

  1. Landgren O, Algernon C, Axdorph U, et al. Hodgkin’s lymphoma in the elderly with special reference to type and intensity of chemotherapy in relation to prognosis. Haematologica. 2003;88(4):438–44.
  2. Engert A, Ballova V, Haverkamp H, et al. Hodgkin’s lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin’s Study Group. J Clin Oncol. 2005;23(22):5052–60. doi: 10.1200/jco.2005.11.080.
  3. Evens AM, Helenowski I, Ramsdale E, et al. A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood. 2012;119(3):692–5. doi: 10.1182/blood-2011-09-378414.
  4. Stark GL, Wood KM, Jack F, et al. Hodgkin’s disease in the elderly: a population-based study. Br J Haematol. 2002;119(2):432–40. doi: 10.1046/j.1365-2141.2002.03815.x.
  5. 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.
  6. Evens AM, Hong F, Gordon LI, et al. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol. 2013;161(1):76–86. doi: 10.1111/bjh.12222.
  7. Ballova V, Ruffer JU, Haverkamp H, et al. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin’s disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005;16(1):124–31. doi: 10.1093/annonc/mdi023.
  8. Halbsguth TV, Nogova L, Mueller H, et al. Phase 2 study of BACOPP (bleomycin, adriamycin, cyclophosphamide,vincristine, procarbazine, and prednisone) in older patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG). Blood. 2010;116(12):2026–32. doi: 10.1182/blood-2009-11-253211.
  9. Levis A, Anselmo AP, Ambrosetti A, et al. VEPEMB in elderly Hodgkin’s lymphoma patients. Results from an Intergruppo Italiano Linfomi (IIL) study. Ann Oncol. 2004;15(1):123–8. doi: 10.1093/annonc/mdh012.
  10. Proctor SJ, Wilkinson J, Jones G, et al. Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study. Blood. 2012;119(25):6005–15. doi: 10.1182/blood-2011-12-396556.
  11. Boll B, Bredenfeld H, Gorgen H, et al. Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma. Blood. 2011;118(24):6292–8. doi: 10.1182/blood-2011-07-368167.
  12. Boll B, Gorgen H, Fuchs M, et al. ABVD in older early stage Hodgkin lymphoma patients treated within the German Hodgkin Study Group (GHSG) HD10 and HD11 Trials. J Clin Oncol. 2013;31(12):1522–9. doi: 10.1200/jco.2012.45.4181.
  13. Weekes CD, Vose JM, Lynch JC, et al. Hodgkin’s disease in the elderly: improved treatment outcome with a doxorubicin-containing regimen. J Clin Oncol. 2002;20(4):1087–93. doi: 10.1200/jco.20.4.1087.
  14. Behringer K, Goergen H, Hitz F, et al. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015;385(9976):1418. doi: 10.1016/s0140-6736(14)61469-0.
  15. Леонтьева А.А., Демина Е.А. Лечение распространенных стадий лимфомы Ходжкина: обзор литературы. Клиническая онкогематология. 2015;8(3):255–66. doi: 10.21320/2500-2139-2015-8-3-255-266.
    [Leont’eva AA, Demina EA. Treatment of Advanced Stage Hodgkin’s Lymphoma: Literature Review. Clinical oncohematology. 2015;8(3):255–66. doi: 10.21320/2500-2139-2015-8-3-255-266. (In Russ)]
  16. Borchmann P, Eichenauer DA, Pluetschow A, et al. Targeted BEACOPP variants in patients with newly diagnosed advanced stage classical Hodgkin lymphoma: Final analysis of a randomized phase II study. Blood. 2015;126:580 (abstract).
  17. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. М.: Буки Веди, 2016. С. 29–30.
    [Poddubnaya IV, Savchenko VG, eds. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. (Russian clinical guidelines in diagnosis and treatment of lymphoproliferative disorders). Moscow: Buki Vedi Publ.; 2016. pp. 29–30. (In Russ)]
  18. Forero-Torres A, Holkova B, Goldschmidt J, et al. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015;126(26):2798–804. doi: 10.1182/blood-2015-06-644336.
  19. Enblad G, Gustavsson A, Sundstrom C, Glimelius B. Patients above sixty years of age with Hodgkin’s lymphoma treated with a new strategy. Acta Oncol. 2002;41(7):659–67. doi: 10.1080/028418602321028283.
  20. Kim HK, Silver B, Li S, et al. Hodgkin’s disease in elderly patients (≥60): Clinical outcome and treatment strategies. Int J Radiat Oncol Biol Phys. 2003;56(2):556–60. doi: 10.1016/s0360-3016(02)04596-0.
  21. Van Spronsen DJ, Janssen-Heijnen MLG, Lemmens VEPP, et al. Independent prognostic effect of co-morbidity in lymphoma patients: results of the population-based Eindhoven Cancer Registry. Eur J Cancer. 2005;41(7):1051–7. doi: 10.1016/j.ejca.2005.01.010.
  22. Macpherson N, Klasa RJ, Gascoyne R, et al. Treatment of elderly Hodgkin’s lymphoma patients with a novel 5-drug regimen (ODBEP): a phase II study. Leuk Lymphoma. 2002;43(7):1395–402. doi: 10.1080/10428190290033332.
  23. Kolstad A, Nome O, Delabie J, et al. Standard CHOP-21 as first line therapy for elderly patients with Hodgkin’s lymphoma. Leuk Lymphoma 2007;48(3):570–6. doi: 10.1080/10428190601126610.
  24. Klimm B, Eich HT, Haverkamp H, et al. Poorer outcome of elderly patients treated with extended-field radiotherapy compared with involved-field radiotherapy after chemotherapy for Hodgkin’s lymphoma: an analysis from the German Hodgkin Study Group. Ann Oncol. 2007;18(2):357–63. doi: 10.1093/annonc/mdl379.

Prognostic and Differential Diagnostic Value of Standardized Uptake Volume (SUV) of Fluorodeoxyglucose in Patients with Hodgkin’s Lymphoma

LYMPHOID TUMORS , ,

AA Rukavitsyn, SI Kurbanov, OA Rukavitsyn

Academician NN Burdenko Principal Military Clinical Hospital under the Ministry of Defence of the Russian Federation, 3 Gospital’naya pl., Moscow, Russian Federation, 105229

For correspondence: Anatolii Anatol’evich Rukavitsyn, 3 Gospital’naya pl., Moscow, Russian Federation, 105229; Tel: +7(499)263-53-17; e-mail: rukavitsin46@gmail.com

For citation: Rukavitsyn AA, Kurbanov SI, Rukavitsyn OA. Prognostic and Differential Diagnostic Value of Standardized Uptake Volume (SUV) of Fluorodeoxyglucose in Patients with Hodgkin’s Lymphoma. Clinical oncohematology. 2017;10(2):182–6 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-182-186

ABSTRACT

Background & Aims. Hodgkin’s lymphoma (HL) is still considered one of the most curable oncohematological diseases of lymphoid tissue. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) combined with multispiral computed tomography (CT) is one of precise and easily available methods of imaging of lymphoid neoplasia. The aim is to determine the correlation between the standardized uptake volume (SUV) of 18F-FDG and results of the first-line anti-tumor treatment of HL patients; to evaluate the possibility of differential diagnosis between HL and diffuse large B-cell lymphomas (DLBCL) based on SUV.

Materials & Methods. 76 patients (69 men and 7 women) aged from 19 to 75 years (median age 36.7 years) with DLBCL (n = 22) and HL (n = 54) were retrospectively enrolled in the study. The diseases were diagnosed over the period from 2011 until 2015. A combined PET-CT imaging was performed for the disease staging.

Results. The comparison of median SUVs in patients with HL (n = 54) and DLBCL (n = 22) demonstrated that the difference had a very high level of significance (p < 0.001). HL patients demonstrated a significantly lower 18F-FDG SUV than DLBCL patients. The analysis of PET findings demonstrated a correlation between the chosen treatment option for the lymphoma and the SUV level (p < 0.001). HL patients demonstrated an insignificant negative correlation between the SUV level rise and the treatment outcome (p = 0.2).

Conclusion. The SUV level does not affect the treatment outcomes of HL patients according to the ABVD protocol, as well as the metabolic response rate and tumor mass reduction. However, the SUV levels significantly differ in patients with HL and DLBCL. These data may be used as additional criteria for differential diagnosis of HL and DLBCL.

Keywords: SUV, PET-CT, Hodgkin’s lymphoma, DLBCL.

Received: November 21, 2016

Accepted: January 23, 2017

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REFERENCES

  1. Гематология: национальное руководство. Под ред. О.А. Рукавицына. М.: ГЭОТАР-Медиа, 2015. 776 с.
    [Rukavitsyn OA, ed. Gematologiya: natsional’noe rukovodstvo. (Hematology: national guidelines.) Moscow: GEOTAR-Media Publ.; 2015. 776 p. (In Russ)]
  2. Campo E, Swerdlow SH, Harris NL, et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019–32. doi: 10.1182/blood-2011-01-293050.
  3. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. J Clin Oncol. 2014;32(27):3059–67. doi: 10.1200/jco.2013.54.8800.
  4. Naumann R, Beuthien-Baumann B, Reiss A, et al. Substantial impact of FDG PET imaging on the therapy decision in patients with early-stage Hodgkin’s lymphoma. Br J Cancer. 2004;90(3):620–5. doi: 10.1038/sj.bjc.6601561.
  5. D’souza MM, Jaimini A, Bansal A, et al. FDG-PET/CT in lymphoma. Indian J Radiol Imaging. 2013;23(4):354–65. doi: 10.4103/0971-3026.125626.
  6. Ngeow JYY, Quek RHH, Ng DCE, et al. High SUV uptake on FDG-PET/CT predicts for an aggressive B-cell lymphoma in a prospective study of primary FDG-PET/CT staging in lymphoma. Ann Oncol. 2009;20(9):1543–7. doi: 10.1093/annonc/mdp030.
  7. Schoder H, Noy A, Gonen M, et al. Intensity of 18Fluorodeoxyglucose Uptake in Positron Emission Tomography Distinguishes Between Indolent and Aggressive Non-Hodgkin’s Lymphoma. J Clin Oncol. 2005;23(21):4643–51. doi: 10.1200/jco.2005.12.072.

 

 

Relevance of Positron-Emission Therapy for Optimization of Treatment of Advanced Hodgkin’s Lymphoma Using Intensive ЕАСОРР-14 Program

LYMPHOID TUMORS , ,

EA Demina1, AA Leont’eva1, GS Tumyan1, YuE Ryabukhina1, EG Medvedovskaya1, OP Trofimova1, VM Sotnikov2, VB Larionova1, EV Paramonova1, LV Manzyuk1, NV Kokosadze1, OV Mukhortova3, IP Aslanidi3, AYu Zaitseva4, LA Radkevich4, MS Rudas5, VA Manukova5, EA Osmanov1

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

2 Russian Scientific Center of Roentgenoradiology under the Ministry of Health of the Russian Federation, 86 bld. 5 Profsoyuznaya str., Moscow, Russian Federation, 117997

3 AN Bakulev Scientific Center for Cardiovascular Surgery, 8 bld. 7 Leninskii pr-t, Moscow, Russian Federation, 117931

4 Clinical Hospital No. 1 under the Administration of Presidential Affairs of the Russian Federation, 45 Losinoostrovskaya str., Moscow, Russian Federation, 107150

5 Central Clinical Hospital under the Administration of Presidential Affairs of the Russian Federation, 15 Marshala Timoshenko str., Moscow, Russian Federation, 121359

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

For citation: Demina EA, Leont’eva AA, Tumyan GS, et al. Relevance of Positron-Emission Therapy for Optimization of Treatment of Advanced Hodgkin’s Lymphoma Using Intensive ЕАСОРР-14 Program. Clinical oncohematology. 2017;10(2):150–7 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-150-157

ABSTRACT

Aim. To evaluate the relevance of the positron-emission therapy (PET) for optimization of the therapy of advanced Hodgkin’s lymphoma (HL) using the intensive EACOPP-14 program.

Materials & Methods. 91 patients with advanced HL (IIX–IIE, III–IV) received the treatment according to the “ЛХМосква1-3” protocol over the period from November 2009 to February 2015, and then the treatment was analyzed. The median age was 29 years (range: 17–50); there were 42 men (46.3 %) and 49 (53.7 %) women. The treatment included 6 cycles of polychemotherapy according to the regimen ЕА(50)СОРР-14 ± radiation therapy. The radiation therapy was performed in 66 patients (72.5 %) after the completion of the chemotherapy. The cumulative focal dose was 30 Gy onto the areas of residual lesions and/or initially large tumor masses.

Results. PET performed during the initial HL diagnosing permited to identify new areas of neoplastic lesions without changes in staging and treatment scheme, as well as specify areas and field size of planned radiation consolidation. The paper confirms the prognostic value of the intermediate PET in patients with advanced HL during the intensive first-line chemotherapy. The intensive therapy at the beginning of the treatment program is associated with higher chances for survival for patients with extremely unfavorable prognosis. After completion of the drug therapy, negative PET findings had a higher prognostic value, than the positive ones. The analysis of the relevance of residual tumor dimensions in the PET negative group demonstrated that the relapses were more common, if the residual tumor was more than 4.5 cm (according to CT findings).

Conclusion. This study confirmed that it reasonable to discuss the discontinuation of the radiation therapy in patients with advanced HL, negative PET findings and small (< 2.5 cm) residual tumor after the intensive ЕАСОРР-14 program. This tactics permits avoiding a number of delayed complications.

Keywords: Hodgkin’s lymphoma, advanced disease, intensive first-line therapy, PET.

Received: January 2, 2017

Accepted: January 14, 2017

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REFERENCES

  1. Diehl V, Franklin J, Pfreundschuh M, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med. 2003;348(24):2386–95. doi: 10.1056/nejmoa022473.
  2. Engert A, Diehl V, Franklin J, et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin’s lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009;27(27):4548–54. doi: 10.1200/jco.2008.19.8820.
  3. Skoetz N, Trelle S, Rancea M, et al. Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin’s lymphoma: a systematic review and network meta-analysis. Lancet Oncol. 2013;14(10):943–52. doi: 10.1016/s1470-2045(13)70341-3.
  4. Hoppe RT. Hodgkin’s disease: Second cancer after treatment Hodgkin’s disease: Complications of therapy and excess mortality. Ann Oncol. 1997;8(1):S115–8. doi: 10.1093/annonc/8.suppl_1.s115.
  5. Шахтарина С.В., Даниленко А.А., Павлов В.В. Злокачественные новообразования у больных лимфомой Ходжкина после лучевой терапии по радикальной программе и комбинированной химиолучевой терапии. Клиническая онкогемотология. 2008;3(1):246–51.
    [Shakhtarina SV, Danilenko AA, Pavlov VV. Secondary malignancies in Hodgkin’s disease patients after radiotherapy and combined chemo-radiotherapy. Klinicheskaya onkogematologiya. 2008;3(1):246–51. (In Russ)]
  6. Ильин Н.В., Виноградова Ю.Н. Поздние осложнения терапии больных лимфомой Ходжкина. Практическая онкология. 2007;8(2):96–101.
    [Il’in NV, Vinogradova YuN. Delayed complications of therapy of patients with Hodgkin’s lymphoma. Prakticheskaya onkologiya. 2007;8(2):96–101. (In Russ)]
  7. Aleman BM, Raemaekers JM, Tirelli U, et al. Involved-field radiotherapy for advanced Hodgkin’s lymphoma. N Engl J Med. 2003;348(24):2396–406. doi: 10.1056/nejmoa022628.
  8. Ferme C, Mounier N, Casasnovas O, et al. Long-term results and competing risk analysis of the H89 trial in patients with advanced-stage Hodgkin lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). Blood. 2006;107(12):4636–42. doi: 10.1182/blood-2005-11-4429.
  9. Johnson PWM, Sydes MR, Hancock BW, et al. Consolidation Radiotherapy in Patients With Advanced Hodgkin’s Lymphoma: Survival Data From the UKLG LY09 Randomized Controlled Trial (ISRCTN97144519). J Clin Oncol. 2010;28(20):3352–9. doi: 10.1200/jco.2009.26.0323.
  10. de Wit M, Bohuslavizki KH, Buchert R, et al. 18FDG-PET following treatment as valid predictor for disease-free survival in Hodgkin’s lymphoma. Ann Oncol. 2001;12(1):29–37. doi: 10.1023/a:1008357126404.
  11. Spaepen K, Stroobants S, Dont P, et al. Can positron emission tomography with [(18F)]-fluorodeoxyglucose after first-line treatment distinguish Hodgkin’s disease patients who need additional therapy from others in whom additional therapy would mean avoidable toxicity? Br J Haematol. 2001;115(2):272–8. doi 10.1046/j.1365-2141.2001.03169.x.
  12. Weihrauch MR, Re D, Scheidhauer K, et al. Thoracic positron emission tomography using 18F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease. Blood. 2001;98(10):2930–4. doi: 10.1182/blood.v98.10.2930.
  13. Kobe C, Dietlein M, Franklin J, et al. Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma. Blood. 2008;112(10):3989–94. doi: 10.1182/blood-2008-06-155820.
  14. Markova J, Kahraman D, Kobe, et al. Role of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography in early and late therapy assessment of patients with advanced Hodgkin lymphoma treated with bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone. Leuk Lymphoma. 2011;53(1):64–70. doi: 10.3109/10428194.2011.603444.
  15. Gallamini A, Hutchings M, Rigacci I, et al. Early interim FDG-PET overshadows the prognostic role of IPS in advanced-stage Hodgkin’s lymphoma treated by conventional ABVD therapy. Haematologica. 2007;32(Suppl 5): Abstract C022.
  16. Radford J, Barrington S, Counsell N, et al. Involved field radiotherapy versus no further treatment in patients with clinical stages IA and IIA Hodgkin lymphoma and a ‘negative’ PET scan after 3 cycles ABVD. Results of the UK NCRI RAPID trial. ASH Annual Meeting Abstracts. 2012;120:547.
  17. Raemaekers JM, Andre MP, Federico M, et al. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014;32(12):1188–94. doi: 10.1200/jco.2013.51.9298.
  18. Picardi M, De Renzo A, Pane F, et al. Randomized comparison of consolidation radiation versus observation in bulky Hodgkin’s lymphoma with post-chemotherapy negative positron emission tomography scans. Leuk Lymphoma. 2007;48(9):1721–7. doi: 10.1080/10428190701559140.
  19. Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. The Lancet. 2012;379(9828):1791–9. doi: 10.1016/s0140-6736(11)61940-5.
  20. Magagnoli M, Marzo K, Balzarotti M, et al. Dimension of residual CT scan mass in Hodgkin’s lymphoma (HL) is a negative prognostic factor in patients with PET negative after chemo+/– radiotherapy. Blood. 2011;118: Abstract 93.
  21. Kobe C, Kuhnert G, Kahraman D, et al. Assessment of Tumor Size Reduction Improves Outcome Prediction of Positron Emission Tomography/Computed Tomograph After Chemotherapy in Advanced-Stage Hodgkin Lymphoma. J Clin Oncol. 2014;32(17):1776–81. doi: 10.1200/jco.2013.53.2507.
  22. Hutchings M. PET Imaging in Lymphoma. Expert Rev Hematol. 2009;2(3):261–76. doi: 10.1586/ehm.09.21.
  23. Gallamini A, Patti C, Viviani S, et al. Early chemotherapy intensification with BEACOPP in advanced stage Hodgkin lymphoma patients with a interim-PET positive after two ABVD courses. Br J Haematol. 2011;152(5):551–60. doi: 10.1111/j.1365-2141.2010.08485.x.
  24. Straus DJ, Pitcher B, Kostakoglu L, et al. Initial Results of US Intergroup Trial of Response-Adapted Chemotherapy or Chemotherapy/Radiation Therapy Based on PET for Non-Bulky Stage I and II Hodgkin Lymphoma (HL) (CALGB/Alliance 50604). Blood. 2015;126(23):578 [Oral and Poster Abstracts].
  25. Press OW, LeBlanc M, Rimsza LM, et al. A phase II trial of response-adapted therapy of stage III-IV Hodgkin lymphoma using early interim FDG-PET imaging: US Intergroup S0816. Hematol Oncol. 2013;31(Suppl 1):137, abstr. 124.
  26. Borchmann P, Haverkamp H, Lohri A, et al. Addition of rituximab to BEACOPPescalated to improve the outcome of early interim PET positive advanced stage Hodgkin lymphoma patients: Second planned interim analysis of the HD18 Study. Blood. 2014;124: Abstract 500.
  27. Cheson BD, Fisher RI, Barrington Sally F, et al. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. J Clin Oncol. 2014;32(27):3059–67. doi: 10.1200/jco.2013.54.8800.
  28. Meyer RM, Gospodarowicz MK, Connors JM, et al. ABVD Alone versus Radiation-Based Therapy in Limited-Stage Hodgkin’s Lymphoma. N Engl J Med. 2012;366(5):399–408. doi: 10.1056/nejmoa1111961.
  29. Cheson BD. Role of functional imaging in the management of lymphoma. J Clin Oncol. 2011;29(14):1844–54. doi: 10.1200/jco.2010.32.5225.
  30. Hutchings M. FDG-PET response-adapted therapy: is 18F-fluorodeoxyglucose positron emission tomography a safe predictor for a change of therapy? Hematol Oncol Clin North Am. 2014;28(1):87–103. doi: 10.1016/j.hoc.2013.10.008.
  31. Barrington SF, Mikhaeel NG. When should FDG-PET be used in the modern management of lymphoma? Br J Haematol. 2013;164(3):315–28. doi: 10.1111/bjh.12601.
  32. Ansell SM, Armitage JO. Positron Emission Tomographic Scans in Lymphoma: Convention and Controversy. Mayo Clin Proc. 2012;87(6):571–80. doi: 10.1016/j.mayocp.2012.03.006.
  33. Gallamini A, Kostakoglu L. Positron emission tomography/computed tomography surveillance in patients with lymphoma: a fox hunt? Haematologica. 2012;97(6):797–9. doi: 10.3324/haematol.2012.063909.

Features of Imaging of Different Types of Hodgkin’s Lymphoma Using Combined Positron Emission and Computed Tomography

LYMPHOID TUMORS , , ,

AS Subbotin1, NG Afanas’eva2

1 Chelyabinsk District Clinical Oncological Dispensary, 42 Blyukhera str., Chelyabinsk, Russian Federation, 454087

2 South Ural State Medical University, 64 Vorovskogo str., Chelyabinsk, Russian Federation, 454092

For correspondence: Aleksei Sergeevich Subbotin, 42 Blyukhera str., Chelyabinsk, Russian Federation, 454087; e-mail: acsubbotin@yandex.ru

For citation: Subbotin AS, Afanas’eva NG. Features of Imaging of Different Types of Hodgkin’s Lymphoma Using Combined Positron Emission and Computed Tomography. Clinical oncohematology. 2017;10(1):61–4(In Russ).

DOI: 10.21320/2500-2139-2017-10-1-61-64

ABSTRACT

Background & Aims. At present, PET-CT has an important clinical significance in Hodgkin’s lymphoma (HL) and is used both for initial tumor staging and restaging and for the evaluation of treatment efficacy. Published data indicate the possible lack of radiotracer accumulation in the tumor tissue in HL before primary treatment. A low metabolic activity of the tumor tissue prior to treatment makes it difficult to assess the treatment dynamics during the anti-tumor therapy. The aim of this work is to determine the incidence of the low metabolic activity of tumor tissue in HL.

Methods. Findings of 131 18F-fluorodeoxyglucose (FDG) whole body PET-CT scans of patients with histologically verified HL (over the period from 2011 to 2015) were studied retrospectively. Patterns of FDG accumulation in different histological types of HL, as well as the levels of metabolic activity in patients with tumor-related toxicity symptoms (B-symptoms) were studied.

Results. The low metabolic activity was detected in 4 % of patients with de novo HL. The highest levels of metabolic activity were detected in nodular sclerosis and the lowest ones in nodular lymphocyte-predominant HL. Higher levels of radiotracer metabolic activity were observed in patients with general symptoms.

Conclusion. In general, a high metabolic activity of the neoplasm is typical for HL. Primary staging before the treatment should be performed for a more accurate evaluation of dynamics of HL treatment outcomes, because in a number of cases a baseline low FDG accumulation in the neoplasm may imitate the absence of a viable tumor tissue in the affected lymph nodes at assessment of treatment results.

Keywords: Hodgkin’s lymphoma, histological types, PET-CT, 18F-fluorodeoxyglucose.

Received: August 25, 2016

Accepted: December 19, 2016

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REFERENCES

  1. Ильин Н.В., Виноградова Ю.Н. Отдаленные последствия лучевой и комбинированной терапии больных лимфомой Ходжкина. Клиническая онкогематология. 2008;1(2):131–5.
    [Ilyin NV, Vinogradova YuN. Late side effects after radio- and combined therapy in patients with Hodgkin’s lymphoma. Klinicheskaya onkogematologiya. 2008;1(2):131–5. (In Russ)]
  2. Курпешев О.К., Павлов В.В., Шкляев С.С. Эффективность локальной гипертермии при химиотерапевтическом и/или лучевом лечении рецидивов лимфомы Ходжкина. Сибирский онкологический журнал. 2013;4(58):28–30.
    [Kupreshev OK, Pavlov VV, Shklyaev SS. Efficacy of local hyperthermia in chemotherapy and/or radiation therapy for recurrences of Hodgkin’s lymphoma. Sibirskii onkologicheskii zhurnal. 2013;4(58):28–30. (In Russ)]
  3. Гранов А.М., Ильин Н.В. (ред.) Лимфомы. СПб.: РНЦРХТ, 2010. С. 222–40.
    [Granov AM, Il’in NV, eds. Limphomy. (Lymphomas.) Saint Petersburg: RNCRHT Publ.; 2010. pp. 222–40. (In Russ)]
  4. Biggi A, Gallamini A, Chauvie S, et al. International validation study for interim PET in ABVD-treated, advanced-stage Hodgkin lymphoma: interpretation criteria and concordance rate among reviewers. J Nucl Med. 2013;54(5):683–90. doi: 10.2967/jnumed.112.110890.
  5. Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32(27):3048–58. doi: 10.1200/jco.2013.53.5229.
  6. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–68. doi: 10.1200/jco.2013.54.8800.
  7. Труфанов Г.Е., Рязанов В.В., Дергунова Н.И. и др. Совмещенная позитронно-эмиссионная и компьютерная томография (ПЭТ-КТ) в онкологии. СПб.: ЭЛБИ-СПб, 2005. 124 c.
    [Trufanov GE, Ryazanov VV, Dergunova NI, et al. Sovmeschennaya pozitronno-emissionnaya i kompyuternaya tomographiya (PET-KT) v onkologii. (Combined positron emission and computed tomography (PET-CT) in oncology.) Saint-Petersburg: ELBI-SPb.; 2005. 124 p. (In Russ)]
  8. Weiler-Sagie M, Bushelev O, Epelbaum R, et al. 18F-FDG Avidity in Lymphoma Readdressed: A Study of 766 Patients. J Nucl Med. 2010;51(1):25–30. doi: 10.2967/jnumed.109.067892.
  9. Tsukamoto N, Kojima M, Hasegawa M, et al. The usefulness of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and a comparison of 18F-FDG-PET with 67gallium scintigraphy in the evaluation of lymphoma: relation to histologic subtypes based on the World Health Organization classification. Cancer. 2007;110(3):652–9. doi: 10.1002/cncr.22807.
  10. Elstrom R, Guan L, Baker G, et al. Utility of FDG-PET scanning in lymphoma by WHO classification. Blood. 2003;101(10):3875–6. doi: 10.1182/blood-2002-09-2778.

 

Role of Positron-Emission Tomography in Prognosis of Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Hodgkin’s Lymphoma

LYMPHOID TUMORS , , ,

VG Potapenko1,2, NB Mikhailova1, BI Smirnov4, IA Skorokhod2, DA Chaginskaya2, VV Ryabchikova2, IA Samorodova2, EI Podol’tseva2, VV Ipatov3, IV Boikov3, VN Semelev3, DA Gornostaev3, TG Potapenko5, TG Kulibaba5, NV Medvedeva2, BV Afanas’ev1

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

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

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

4 VI Ul’yanov (Lenin) St. Petersburg State Electrotechnical University LETI, 5 Professora Popova str., Saint Petersburg, Russian Federation, 197376

5 St. Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

For correspondence: Vsevolod Gennad’evich Potapenko, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel: +7(812)230-19-33; е-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Mikhailova NB, Smirnov BI, et al. Role of Positron-Emission Tomography in Prognosis of Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Hodgkin’s Lymphoma. Clinical oncohematology. 2016;9(4):406–12 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-406-412

ABSTRACT

Aim. To perform a comparative analysis of the prognostic significance of positron-emission tomography (PET) with other prognostic factors of the efficacy of high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with Hodgkin’s lymphoma.

Methods. Data on 84 patients with Hodgkin’s lymphoma receiving treatment over the period from October 2007 till November 2015 were analyzed. The median age was 26.6 years (range: 10–62). The median follow-up was 25 months (range: 1–81 months). The prognostic significance of sex, response to the initial chemotherapy, time to relapse, second-line chemotherapy regimen type, B-symptoms, tumor size (>5 cm in cases of relapse prior to the HDCT), serum LDH and albumin levels, CT findings, the number of chemotherapy lines, conditioning regimen before the auto-HSCT, and the metabolic activity before the HDCT (PET1, n = 82) and after auto-HSCT (PET2, n = 57) was analyzed.

Results. The two-year overall (OS) and event-free (EFS) survival rates were 70.6 % and 58.7%, respectively. Prognosis was the worst in patients with CT-confirmed lymphoma progression by the initiation of HDCT. In the presence of a CT-response, the PET status of lymphoma has a prognostic significance. The 2-year OS and EFS rates of PET1-negative and PET1-positive patients were 82 % vs. 62 % (p = 0.056) and 74 % vs. 44 % (p = 0.003), respectively. In PET2-negative and PET2-positive patients, the OS and EFS rates were 90 % vs. 65 % (p = 0.013) and 72 % vs. 52 % (p = 0.014), respectively. From the prognostic point of view, PET2 findings prevailed over PET1 findings. The multivariate analysis confirmed only PET2 significance for OS prediction.

Conclusion. The tumor sensitivity to the chemotherapy assessed by the CT is the most important prognostic factor. In case of a positive CT dynamics, the achievement of PET1 or PET2 negativity before or after HDCT/auto-HSCT is a favorable prognostic factor. The worst prognosis was observed in patients with tumor metabolic activity before or after HDCT/auto-HSCT.

Keywords: positron-emission tomography (PET), Hodgkin’s lymphoma, high-dose chemotherapy, auto-HSCT.

Received: June 23, 2016

Accepted: August 29, 2016

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REFERENCES

  1. Жуков Н.В., Румянцев А.Г., Усс А.Л. и др. Эффективность и безопасность высокодозной химиотерапии с аутологичной трансплантацией гемопоэтических стволовых клеток у больных с неблагоприятным течением лимфомы Ходжкина. Опыт трансплантационных центров России, Украины и республики Беларусь. Вопросы гематологии, онкологии и иммунопатологии в педиатрии. 2014;13(1): 22–31.
    [Zhukov NV, Rumyantsev AG, Uss AL, et al. Efficacy and safety of high-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with unfavorable course of Hodgkin’s lymphoma. Experience of transplantation centers in Russia, Ukraine, and Belarus. Voprosy gematologii, onkologii i immunopatologii v pediatrii. 2014;13(1):22–31. (In Russ)]
  2. Федоренко Д.А., Мельниченко В.Я., Ионова Т.И. и др. Клиническая оценка эффективности аутологичной трансплантации кроветворных стволовых клеток при лимфомах. Вестник Национального медико-хирургического центра им. Н.И. Пирогова. 2013;8(4):62–5.
    [Fedorenko DA, Mel’nichenko VYa, Ionova TI, et al. Clinical evaluation of efficacy of autologous hematopoietic stem cell transplantation in lymphomas. Vestnik Natsional’nogo mediko-khirurgicheskogo tsentra im. N.I. Pirogova. 2013;8(4):62–5. (In Russ)]
  3. Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32(27):3048–58. doi: 10.1200/jco.2013.53.5229.
  4. Асланиди И.П., Мухортова О.В., Шурупова И.В. и др. Позитронно-эмиссионная томография: уточнение стадии болезни при злокачественных лимфомах. Клиническая онкогематология. 2010;3(2):119–29.
    [Aslanidis IP, Mukhortova OV, Shurupova IV, et al. Positron emission tomography for staging of patients with malignant lymphomas. Klinicheskaya onkogematologiya. 2010;3(2):119–29. (In Russ)]
  5. Moskowitz СH, Yahalom J, Zelenetz AD. High-dose chemo-radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre-transplant functional imaging. Br J Haematol. 2010;148(6):890–7. doi: 10.1111/j.1365-2141.2009.08037.x.
  6. Nieto Y, Popat U, Anderlini P, et al. Autologous stem cell transplantation for refractory or poor-risk relapsed Hodgkin’s lymphoma: effect of the specific high-dose chemotherapy regimen on outcome. Biol Blood Marrow Transplant. 2013;19(3):410–7. doi: 10.1016/j.bbmt.2012.10.029.
  7. Schot BW, Zijlstra JM, Sluiter WJ, et al. Early FDG-PET assessment in combination with clinical risk scores determines prognosis in recurring lymphoma. Blood. 2007;109(2):486–91. doi: 10.1182/blood-2005-11-006957.
  8. Spaepen K, Stroobants S, Dupont P, et al. Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high dose chemotherapy and stem cell transplantation. Blood. 2003;102(1):53–9. doi: 10.1182/blood-2002-12-3842.
  9. Svoboda J, Andreadis C, Elstrom R, et al. Prognostic value of FDG-PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation. Bone Marrow Transplant. 2006;38(3):211–6. doi: 10.1038/sj.bmt.1705416.
  10. Becherer A, Mitterbauer M, Jaeger U, et al. Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation. Leukemia. 2002;16(2):260–7. doi: 10.1038/sj.leu.2402342.
  11. Filmont JE, Czernin J, Yap C, et al. Value of F-18 fluorodeoxyglucose positron emission tomography for predicting the clinical outcome of patients with aggressive lymphoma prior to and after autologous stem-cell transplantation. Chest. 2003;124(2):608–13. doi: 10.1378/chest.124.2.608.
  12. Devillier R, Coso D, Castagna L, et al. Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy. Haematologica. 2012;97(7):1073–9. doi: 10.3324/haematol.2011.056051.
  13. Arai S, Letsinger R, Wong RM, et al. Phase I/II trial of GN-BVC, a gemcitabine and vinorelbine-containing conditioning regimen for autologous hematopoietic cell transplantation in recurrent and refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2010;16(8):1145–54. doi: 10.1016/j.bbmt.2010.02.022.
  14. Castagna L, Bramanti S, Balzarotti M, et al. Predictive value of early 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) during salvage chemotherapy in relapsing/refractory Hodgkin lymphoma (HL) treated with high-dose chemotherapy. Br J Haematol. 2009;145(3):369–72. doi: 10.1111/j.1365-2141.2009.07645.x.
  15. Akhtar S, Al-Sugair AS, Abouzied M, et al. Pre-transplant FDG-PET-based survival model in relapsed and refractory Hodgkin’s lymphoma: outcome after high-dose chemotherapy and auto-SCT. Bone Marrow Transplant. 2013;48(12):1530–6. doi: 10.1038/bmt.2013.88.
  16. Crocchiolo R, Canevari C, Assanelli A, et al. Pre-transplant 18FDG-PET predicts outcome in lymphoma patients treated with high-dose sequential chemotherapy followed by autologous stem cell transplantation. Leuk Lymphoma. 2008;49(4):727–33. doi: 10.1080/10428190701885545.
  17. Gentzler RD, Evens AM, Rademaker AW, et al. F-18 FDG-PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem-cell transplantation for relapsed and refractory Hodgkin lymphoma. Br J Haematol. 2014;165(6):793–800. doi: 10.1111/bjh.12824.
  18. Jabbour E, Hosing C, Ayers G, et al. Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma. Cancer. 2007;109(12):2481–9. doi: 10.1002/cncr.22714.
  19. Cohen JB, Hall NC, Ruppert AS, et al. Association of pre-transplantation positron emission tomography/computed tomography and outcome in mantle-cell lymphoma. Bone Marrow Transplant. 2013;48(9):1212–7. doi: 10.1038/bmt.2013.46.
  20. Dickinson M, Hoyt R, Roberts AW, et al. Improved survival for relapsed diffuse large B cell lymphoma is predicted by a negative pre-transplant FDG-PET scan following salvage chemotherapy. Br J Haematol. 2010;150(1):39–45. doi: 10.1111/j.1365-2141.2010.08162.x.
  21. Palmer J, Goggins T, Broadwater G, et al. Early post transplant (F-18) 2-fluoro-2-deoxyglucose positron emission tomography does not predict outcome for patients undergoing auto-SCT in non-Hodgkin and Hodgkin lymphoma. Bone Marrow Transplant. 2011;46(6):847–51. doi: 10.1038/bmt.2010.203.
  22. Alousi AM, Saliba RM, Okoroji GJ, et al. Disease staging with positron emission tomography or gallium scanning and use of rituximab predict outcome for patients with diffuse large B-cell lymphoma treated with autologous stem cell transplantation. Br J Haematol. 2008;142(5):786–92. doi: 10.1111/j.1365-2141.2008.07277.x.
  23. Bondly C, Johnston PB, Lowe V, et al. Positive positron emission tomography (PET) pre-autologous stem cell transplant (ASCT) in non-Hodgkin lymphoma (NHL) does not preclude successful outcome. Biol Blood Marrow Transplant. 2006;12(2):18–9. doi: 10.1016/j.bbmt.2005.11.060.
  24. Qiao W, Zhao J, Xing Y. Predictive value of [18F]fluoro-2-deoxy-D-glucose positron emission tomography for clinical outcome in patients with relapsed/refractory diffuse large B-cell lymphoma prior to and after autologous stem cell transplant. Leuk Lymphoma. 2014;55(2):276–82. doi: 10.3109/10428194.2013.797974.
  25. Sucak GT, Ozkurt ZN, Suyani E, et al. Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival. Ann Hematol. 2011;90(11):1329–36. doi: 10.1007/s00277-011-1209-0.
  26. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008.
  27. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86. doi: 10.1200/jco.2006.09.2403.
  28. David G, Kleinbaum MK. Survival Analysis. A Self-Learning Text. 2nd edition. Springer; 2002. рр. 583. doi: 10.1111/j.1541-0420.2006.00540_18.x.
  29. Петрова Г.Д., Мелкова К.Н., Чернявская Т.З. и др. Первично-рефрактерное течение лимфомы Ходжкина и аутологичная трансплантация гемопоэтических стволовых клеток. Результаты одноцентрового проспективного исследования. Российский онкологический журнал. 2015;20(3):4–11.
    [Petrova GD, Melkova KN, Chernyavskaya TZ, et al. Primary refractory Hodgkin’s lymphoma and autologous stem cell transplantation: results of the single-center prospective study. Rossiiskii onkologicheskii zhurnal. 2015;20(3):4–11. (In Russ)]
  30. Crocchiolo R, Fallanca F, Giovacchini G, et al. Role of 18FDG-PET/CT in detecting relapse during follow-up of patients with Hodgkin’s lymphoma. Ann Hematol. 2009;88(12):1229–36. doi: 10.1007/s00277-009-0752-4.
  31. Gupta D, Lis ChG. Pretreatment Serum Albumin as a Predictor of Cancer Survival: A Systematic Review of the Epidemiological Literature. Nutrition J. 2010;9(1):69–116. doi: 10.1186/1475-2891-9-69.
  32. Демина Е.А. Лимфома Ходжкина: прогностические признаки сегодня. Современная онкология. 2006;4:4–7.
    [Demina EA. Hodgkin’s lymphoma: prognostic factors today. Sovremennaya onkologiya. 2006;4:4–7. (In Russ)]
  33. Czyz A, Lojko-Dankowska A, Dytfeld D, et al. Prognostic factors and long-term outcome of autologous haematopoietic stem cell transplantation following a uniform-modified BEAM-conditioning regimen for patients with refractory or relapsed Hodgkin lymphoma: a single-center experience. Med Oncol. 2013;30(3):611. doi: 10.1007/s12032-013-0611-y.
  34. Villa D, Seshadri T, Puig N, et al. Second-line salvage chemotherapy for transplant-eligible patients with Hodgkin’s lymphoma resistant to platinum-containing first-line salvage chemotherapy. Haematologica. 2012;97(5):751–7. doi: 10.3324/haematol.2011.047670.
  35. Colpo A, Hochberg E, Chen YB. Current status of autologous stem cell transplantation in relapsed and refractory Hodgkin’s lymphoma. Oncologist. 2012;17(1):80–90. doi: 10.1634/theoncologist.2011-0177.

Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas

LYMPHOID TUMORS , , ,

EA Demina

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

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

For citation: Demina EA. Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas. Clinical oncohematology. 2016;9(4):398–405 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-398-405

ABSTRACT

The concept of total curability of Hodgkin’s lymphoma was introduced as early as in 1970s. However, 10–30 % of patients develop relapses; in addition, resistant tumors cannot be excluded. A high-dose chemotherapy with autologous hematopoietic stem cell transplantation is a modern treatment standard for relapses and refractory Hodgkin’s lymphomas. However, long-term remissions are achieved only in a half of these patients. The toxicity of effective first-line treatment regimens and insufficient effectiveness of regimens prescribed for relapses and refractory disease are the reason for further search of new therapeutic options for this malignant tumor. Invention of an immunoconjugate, brentuximab vedotin, became one of the new steps in the treatment of Hodgkin’s lymphomas. This review presents data on the pharmacological properties of the drug, the mechanism of the anti-tumor effect, as well as results of large international, randomized clinical trials.

Keywords: brentuximab vedotin, Hodgkin’s lymphoma, relapse, treatment.

Received: June 14, 2016

Accepted: June 17, 2016

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REFERENCES

  1. De Vita VT. The consequences of the chemotherapy of Hodgkin’s disease: the 10th David A. Karnofsky memorial lecture. Cancer. 1981;47(1):1–13. doi: 10.1002/1097-0142(19810101)47:1<1::AID-CNCR2820470102>3.0.co;2-2.
  2. Engert A, Younes A, eds. Hematologic malignancies: Hodgkin lymphoma. 2nd edition. A Comprehensive Update on Diagnostics and Clinics. Berlin Heidelberg: Springer; 2015. doi: 10.1007/978-3-319-12505-3.
  3. Horning S, Fanale M, deVos S, et al. Defining a population of Hodgkin lymphoma patients for novel therapeutics: An international effort. Ann Oncol. 2008;19(Suppl 4): Abstract 118.
  4. Falini B, Pileri S, Pizzolo G, et al. CD30 (Ki-1) molecule: A new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. Blood. 1995;85(1):1–14.
  5. Matsumoto K, Terakawa M, Miura K, et al. Extremely rapid and intense induction of apoptosis in human eosinophils by anti-CD30 antibody treatment in vitro. J Immunol. 2004;172(4):2186–93. doi: 10.4049/jimmunol.172.4.2186.
  6. Ansell SM, Horwitz SM, Engert A, et al. Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin’s lymphoma and anaplastic large-cell lymphoma. J Clin Oncol. 2007;25(19):2764–9. doi: 10.1200/jco.2006.07.8972.
  7. Forero-Torres A, Leonard JP, Younes A, et al. A Phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Br J Haematol. 2009;146(2):171–9. doi: 10.1111/j.1365-2009.07740.x.
  8. Dosio F, Brusa P and Cattel L Immunotoxins and Anticancer Drug Conjugate Assemblies: The Role of the Linkage between Components. 2011;3(12):848–83. doi: 10.3390/toxins3070848.
  9. Francisco JA, Cerveny CG, Meyer DL, et al. cAC10-vcMMAE, an anti-CD30–monomethyl auristatin E conjugate with potent and selective antitumor activity. 2003;102(4):1458–65. doi: 10.1182/blood-2003-01-0039.
  10. Sutherland MSK, Sanderson RJ, Gordon KA, et al. Lysosomal Trafficking and Cysteine Protease Metabolism Confer Target-specific Cytotoxicity by Peptide-linked Anti-CD30-Auristatin Conjugates. J Biol Chem. 2006;281(15):10540–7. doi: 10.1074/jbc.M510026200.
  11. Katz J, Janik JA, Yones A. Brentuximab vedotin (SGN-35). Clin Cancer Res. 2011;17(20):6428–36. doi: 10.1158/1078-0432.CCR-11-0488.
  12. Chen R, Gopal AK, Smith SE, et al. Five-year survival data demonstrating durable responses from a pivotal phase 2 study of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2015;126(Suppl 23): Abstract 2736. doi: 10.1182/blood-2016-02-699850.
  13. Gardai SJ, Epp A, Law C-L. Brentuximab vedotin-mediated immunogenic cell death. Cancer Res. 2015;75(15): Abstract 2469. doi: 10.1158/1538-7445.am2015-2469.
  14. Oflazoglu E, Stone IJ, Gordon KA. Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30. Blood. 2007;110(13):4370–2. doi: 10.1182/blood-2007-06-097014.
  15. Fu L, Xinqun Z, Kim E, et al. Relationship between in vivo antitumor activity of ADC and payload release in preclinical models. Cancer Res. 2014;74(19): Abstract 3694. doi: 10.1158/1538-am2014-3694.
  16. Kim YH, Tavallaee M, Sundram U, et al. Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sezary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol. 2015;33(32):3750–8. doi: 10.1200/jco.2014.60.3969.
  17. Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30(18):2183–9. doi: 10.1200/jco.2011.38.0410.
  18. Arai S, Fanale M, DeVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell Leuk Lymphoma. 2013;54(11):2531–3. doi: 10.3109/10428194.2013.798868.
  19. Gopal AK, Chen R, Smith SE, et al. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015;125(8):1236–43. doi: 10.1182/blood-2014-08-595801.
  20. Lee JJ, Swain SM. Peripheral neuropathy induced by microtubule-stabilizing agents. J Clin Oncol. 2006;24(10):1633–42. doi: 10.1200/jco.2005.04.0543.
  21. Swain SM, Arezzo JC. Neuropathy associated with microtubule inhibitors: Diagnosis, incidence, and management. Clin Adv Hematol Oncol. 2008;6(6):455–67.
  22. Zinzani PL, Corradini P, Gianni AM, et al. Brentuximab Vedotin in CD30-Positive Lymphomas: A SIE, SIES, and GITMO Position Paper. Clin Lymph Myel Leuk. 2015;15(9):507–13. doi: 10.1016/j.clml.2015.06.008.
  23. Rothe A, Sasse S, Goergen H, et al. Brentuximab vedotin for relapsed or refractory CD30 hematologic malignancies: the German Hodgkin Study Group experience. Blood. 2012;120(7):1470–2. doi: 10.1182/blood-2012-05-430918.
  24. Gibb A, Jones C, Bloor A, et al. Brentuximab vedotin in refractory CD30 lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. Haematologica. 2013;98(4):611–4. doi: 10.3324/haematol.2012.069393.
  25. Zinzani PL, Viviani S, Anastasia A, et al. Brentuximab vedotin in relapsed/refractory Hodgkin’s lymphoma: the Italian experience and results of its use in daily clinical practice outside clinical trials. Haematologica. 2013;98(8):1232–6. doi: 10.3324/haematol.2012.083048.
  26. Perrot A, Monjanel H, Bouabdallah R, et al. Brentuximab vedotin as single agent in refractory or relapsed CD30-positive Hodgkin lymphoma: the French name patient program experience in 241 patients. Haematologica. 2014;99(s1):498, abstr. S1293.
  27. Perrot A, Monjanel H, Bouabdallah R, et al. Lymphoma Study Association (LYSA). Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program. 2016;101(4):466–73. doi: 10.3324/haematol.2015.134213. Epub 2016 Jan 14.
  28. Moskowitz CH, Yahalom J, Zelenetz AD, et al. High-Dose Chemo-Radiotherapy for Relapsed or Refractory Hodgkin Lymphoma and the Significance of Pre-transplant Functional Imaging. Br J Haematol. 2010;148(6):890–7. doi: 10.1111/j.1365-2141.2009.08037.x.
  29. Moskowitz AJ, Schoder H, Gerecitano JF. FDG-PET Adapted Sequential Therapy with Brentuximab Vedotin and Augmented ICE Followed By Autologous Stem Cell Transplant for Relapsed and Refractory Hodgkin Lymphoma. Blood (ASH Annual Meeting Abstracts). 2013;122(21): Abstract 2099.
  30. Moskowitz AJ, Hamlin PA Jr, Perales M-A, et al. Phase II Study of Bendamustine in Relapsed and Refractory Hodgkin Lymphoma. J Clin Oncol. 2013;31(4):456–60. doi: 10.1200/jco.2012.45.3308.
  31. LaCasce A, Sawas A, Bociek RG, et al. A phase 1/2 single-arm, open-label study to evaluate the safety and efficacy of brentuximab vedotin in combination with bendamustine for patients with Hodgkin lymphoma in the first salvage setting: interim results. Biol Blood Marrow Transplant. 2014;20(2):S161. doi: 10.1016/j.bbmt.2013.12.257.
  32. Aparicio J, Segura A. Garcera S, et al. ESHAP is an Active Regimen for Relapsing Hodgkin’s Disease. Ann Oncol. 1999;10(5):593–5. doi: 10.1023/A:1026454831340.
  33. Garcia-Sanz R, Sureda A, Alonso-Alvarez S, et al. Evaluation of the Regimen Brentuximab Vedotin Plus ESHAP (BRESHAP) in Refractory or Relapsed Hodgkin Lymphoma Patients: Preliminary Results of a Phase I-II Trial from the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO). Blood. 2015: Abstract 582.
  34. Bartlett NL, Chen R, Fanale MA, et al. Retreatment with brentuximab vedotin in CD30-positive hematologic malignancies. J Hematol Oncol. 2014;7(1):24. doi: 10.1186/1756-8722-7-24.
  35. Batlevi CL, Younes A. Novel therapy for Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program. 2013;2013(1):394–9. doi: 10.1182/asheducation-2013.1.394.
  36. Majhail NS, Weisdorf DJ, Defor TE, et al. Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin’s lymphoma. Biol Blood Marrow Transplant. 2006;12(10):1065–72. doi: 10.1016/j.bbmt.2006.06.006.
  37. Moskowitz CH, Paszkiewicz-Kozik E, Nadamanee A, et al. Analysis of primary-refractory Hodgkin lymphoma pts in a randomized, placebo-controlled study of brentuximab vedotin consolidation after autologous stem cell transplant. Hematol Oncol. 2015;33:165, abstr. 120.
  38. Moskowitz CH, Nademanee A, Masszi T, et Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385(9980):1853–62. doi: 10.1016/S0140-6736(15)60165-9.
  39. Walewski JA, Nademanee A, Masszi T, et al. Multivariate analysis of PFS from the AETHERA trial: a phase 3 study of brentuximab vedotin consolidation after autologous stem cell transplant for HL. J Clin Oncol. 2015;33(Suppl): Abstract 8519.
  40. Sweetenham JW, Walewski J, Nadamanee A, et al. Updated Efficacy and Safety Data from the AETHERA Trial of Consolidation with Brentuximab Vedotin after Autologous Stem Cell Transplant (ASCT) in Hodgkin Lymphoma Patients at High Risk of Relapse. Biol Blood Marrow Transplant. 2016;22(3):S19e–S481, abstr. 24. doi: 10.1016/j.bbmt.2015.11.315.
  41. Bonthapally V, Ma E, Viviani S, et al. Healthcare utilization in the AETHERA trial: phase 3 study of brentuximab vedotin in patients at increased risk of residual Hodgkin lymphoma post-ASCT. Hematol Oncol. 2015;33:193, abstr. 177.
  42. Kuruvilla J, Connors JM, Sawas A, et al. A phase 1 study of brentuximab vedotin (BV) and bendamustine (B) in relapsed or refractory Hodgkin lymphoma (HL) and anaplastic large T-cell lymphoma (ALCL). Hematol Oncol. 2015;33:148, abstr. 090.
  43. Theurich S, Malcher J, Wennhold K, et al. Brentuximab Vedotin Combined With Donor Lymphocyte Infusions for Early Relapse of Hodgkin Lymphoma After Allogeneic Stem-Cell Transplantation Induces Tumor-Specific Immunity and Sustained Clinical Remission. J Clin Oncol. 2013;31(5):e59–e63. doi: 10.1200/jco.2012.43.6832.
  44. Vaklavas C, Forero-Torres A. Safety and efficacy of brentuximab vedotin in patients with Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Ther Adv Hematol. 2012;3(4):209–25. doi: 10.1177/2040620712443076.

Role of Positron-Emission Tomography in Prognosis of Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Hodgkin’s Lymphoma

LYMPHOID TUMORS , , ,

VG Potapenko1,2, NB Mikhailova1, BI Smirnov4, IA Skorokhod2, DA Chaginskaya2, VV Ryabchikova2, IA Samorodova2, EI Podol’tseva2, VV Ipatov3, IV Boikov3, VN Semelev3, DA Gornostaev3, TG Potapenko5, TG Kulibaba5, NV Medvedeva2, BV Afanas’ev1

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

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

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

4 VI Ul’yanov (Lenin) St. Petersburg State Electrotechnical University LETI, 5 Professora Popova str., Saint Petersburg, Russian Federation, 197376

5 St. Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

For correspondence: Vsevolod Gennad’evich Potapenko, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel: +7(812)230-19-33; е-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Mikhailova NB, Smirnov BI, et al. Role of Positron-Emission Tomography in Prognosis of Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Hodgkin’s Lymphoma. Clinical oncohematology. 2016;9(4):406–12 (In Russ).

DOI: http://dx.doi.org/10.21320/2500-2139-2016-9-4-406-412

ABSTRACT

Aim. To perform a comparative analysis of the prognostic significance of positron-emission tomography (PET) with other prognostic factors of the efficacy of high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with Hodgkin’s lymphoma.

Methods. Data on 84 patients with Hodgkin’s lymphoma receiving treatment over the period from October 2007 till November 2015 were analyzed. The median age was 26.6 years (range: 10–62). The median follow-up was 25 months (range: 1–81 months). The prognostic significance of sex, response to the initial chemotherapy, time to relapse, second-line chemotherapy regimen type, B-symptoms, tumor size (>5 cm in cases of relapse prior to the HDCT), serum LDH and albumin levels, CT findings, the number of chemotherapy lines, conditioning regimen before the auto-HSCT, and the metabolic activity before the HDCT (PET1, n = 82) and after auto-HSCT (PET2, n = 57) was analyzed.

Results. The two-year overall (OS) and event-free (EFS) survival rates were 70.6 % and 58.7%, respectively. Prognosis was the worst in patients with CT-confirmed lymphoma progression by the initiation of HDCT. In the presence of a CT-response, the PET status of lymphoma has a prognostic significance. The 2-year OS and EFS rates of PET1-negative and PET1-positive patients were 82 % vs. 62 % (p = 0.056) and 74 % vs. 44 % (p = 0.003), respectively. In PET2-negative and PET2-positive patients, the OS and EFS rates were 90 % vs. 65 % (p = 0.013) and 72 % vs. 52 % (p = 0.014), respectively. From the prognostic point of view, PET2 findings prevailed over PET1 findings. The multivariate analysis confirmed only PET2 significance for OS prediction.

Conclusion. The tumor sensitivity to the chemotherapy assessed by the CT is the most important prognostic factor. In case of a positive CT dynamics, the achievement of PET1 or PET2 negativity before or after HDCT/auto-HSCT is a favorable prognostic factor. The worst prognosis was observed in patients with tumor metabolic activity before or after HDCT/auto-HSCT.

Keywords: positron-emission tomography (PET), Hodgkin’s lymphoma, high-dose chemotherapy, auto-HSCT.

Received: June 23, 2016

Accepted: August 29, 2016

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REFERENCES

  1. Жуков Н.В., Румянцев А.Г., Усс А.Л. и др. Эффективность и безопасность высокодозной химиотерапии с аутологичной трансплантацией гемопоэтических стволовых клеток у больных с неблагоприятным течением лимфомы Ходжкина. Опыт трансплантационных центров России, Украины и республики Беларусь. Вопросы гематологии, онкологии и иммунопатологии в педиатрии. 2014;13(1): 22–31.
    [Zhukov NV, Rumyantsev AG, Uss AL, et al. Efficacy and safety of high-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with unfavorable course of Hodgkin’s lymphoma. Experience of transplantation centers in Russia, Ukraine, and Belarus. Voprosy gematologii, onkologii i immunopatologii v pediatrii. 2014;13(1):22–31. (In Russ)]
  2. Федоренко Д.А., Мельниченко В.Я., Ионова Т.И. и др. Клиническая оценка эффективности аутологичной трансплантации кроветворных стволовых клеток при лимфомах. Вестник Национального медико-хирургического центра им. Н.И. Пирогова. 2013;8(4):62–5.
    [Fedorenko DA, Mel’nichenko VYa, Ionova TI, et al. Clinical evaluation of efficacy of autologous hematopoietic stem cell transplantation in lymphomas. Vestnik Natsional’nogo mediko-khirurgicheskogo tsentra im. N.I. Pirogova. 2013;8(4):62–5. (In Russ)]
  3. Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32(27):3048–58. doi: 10.1200/jco.2013.53.5229.
  4. Асланиди И.П., Мухортова О.В., Шурупова И.В. и др. Позитронно-эмиссионная томография: уточнение стадии болезни при злокачественных лимфомах. Клиническая онкогематология. 2010;3(2):119–29.
    [Aslanidis IP, Mukhortova OV, Shurupova IV, et al. Positron emission tomography for staging of patients with malignant lymphomas. Klinicheskaya onkogematologiya. 2010;3(2):119–29. (In Russ)]
  5. Moskowitz СH, Yahalom J, Zelenetz AD. High-dose chemo-radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre-transplant functional imaging. Br J Haematol. 2010;148(6):890–7. doi: 10.1111/j.1365-2141.2009.08037.x.
  6. Nieto Y, Popat U, Anderlini P, et al. Autologous stem cell transplantation for refractory or poor-risk relapsed Hodgkin’s lymphoma: effect of the specific high-dose chemotherapy regimen on outcome. Biol Blood Marrow Transplant. 2013;19(3):410–7. doi: 10.1016/j.bbmt.2012.10.029.
  7. Schot BW, Zijlstra JM, Sluiter WJ, et al. Early FDG-PET assessment in combination with clinical risk scores determines prognosis in recurring lymphoma. Blood. 2007;109(2):486–91. doi: 10.1182/blood-2005-11-006957.
  8. Spaepen K, Stroobants S, Dupont P, et al. Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high dose chemotherapy and stem cell transplantation. Blood. 2003;102(1):53–9. doi: 10.1182/blood-2002-12-3842.
  9. Svoboda J, Andreadis C, Elstrom R, et al. Prognostic value of FDG-PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation. Bone Marrow Transplant. 2006;38(3):211–6. doi: 10.1038/sj.bmt.1705416.
  10. Becherer A, Mitterbauer M, Jaeger U, et al. Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation. Leukemia. 2002;16(2):260–7. doi: 10.1038/sj.leu.2402342.
  11. Filmont JE, Czernin J, Yap C, et al. Value of F-18 fluorodeoxyglucose positron emission tomography for predicting the clinical outcome of patients with aggressive lymphoma prior to and after autologous stem-cell transplantation. Chest. 2003;124(2):608–13. doi: 10.1378/chest.124.2.608.
  12. Devillier R, Coso D, Castagna L, et al. Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy. Haematologica. 2012;97(7):1073–9. doi: 10.3324/haematol.2011.056051.
  13. Arai S, Letsinger R, Wong RM, et al. Phase I/II trial of GN-BVC, a gemcitabine and vinorelbine-containing conditioning regimen for autologous hematopoietic cell transplantation in recurrent and refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2010;16(8):1145–54. doi: 10.1016/j.bbmt.2010.02.022.
  14. Castagna L, Bramanti S, Balzarotti M, et al. Predictive value of early 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) during salvage chemotherapy in relapsing/refractory Hodgkin lymphoma (HL) treated with high-dose chemotherapy. Br J Haematol. 2009;145(3):369–72. doi: 10.1111/j.1365-2141.2009.07645.x.
  15. Akhtar S, Al-Sugair AS, Abouzied M, et al. Pre-transplant FDG-PET-based survival model in relapsed and refractory Hodgkin’s lymphoma: outcome after high-dose chemotherapy and auto-SCT. Bone Marrow Transplant. 2013;48(12):1530–6. doi: 10.1038/bmt.2013.88.
  16. Crocchiolo R, Canevari C, Assanelli A, et al. Pre-transplant 18FDG-PET predicts outcome in lymphoma patients treated with high-dose sequential chemotherapy followed by autologous stem cell transplantation. Leuk Lymphoma. 2008;49(4):727–33. doi: 10.1080/10428190701885545.
  17. Gentzler RD, Evens AM, Rademaker AW, et al. F-18 FDG-PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem-cell transplantation for relapsed and refractory Hodgkin lymphoma. Br J Haematol. 2014;165(6):793–800. doi: 10.1111/bjh.12824.
  18. Jabbour E, Hosing C, Ayers G, et al. Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma. Cancer. 2007;109(12):2481–9. doi: 10.1002/cncr.22714.
  19. Cohen JB, Hall NC, Ruppert AS, et al. Association of pre-transplantation positron emission tomography/computed tomography and outcome in mantle-cell lymphoma. Bone Marrow Transplant. 2013;48(9):1212–7. doi: 10.1038/bmt.2013.46.
  20. Dickinson M, Hoyt R, Roberts AW, et al. Improved survival for relapsed diffuse large B cell lymphoma is predicted by a negative pre-transplant FDG-PET scan following salvage chemotherapy. Br J Haematol. 2010;150(1):39–45. doi: 10.1111/j.1365-2141.2010.08162.x.
  21. Palmer J, Goggins T, Broadwater G, et al. Early post transplant (F-18) 2-fluoro-2-deoxyglucose positron emission tomography does not predict outcome for patients undergoing auto-SCT in non-Hodgkin and Hodgkin lymphoma. Bone Marrow Transplant. 2011;46(6):847–51. doi: 10.1038/bmt.2010.203.
  22. Alousi AM, Saliba RM, Okoroji GJ, et al. Disease staging with positron emission tomography or gallium scanning and use of rituximab predict outcome for patients with diffuse large B-cell lymphoma treated with autologous stem cell transplantation. Br J Haematol. 2008;142(5):786–92. doi: 10.1111/j.1365-2141.2008.07277.x.
  23. Bondly C, Johnston PB, Lowe V, et al. Positive positron emission tomography (PET) pre-autologous stem cell transplant (ASCT) in non-Hodgkin lymphoma (NHL) does not preclude successful outcome. Biol Blood Marrow Transplant. 2006;12(2):18–9. doi: 10.1016/j.bbmt.2005.11.060.
  24. Qiao W, Zhao J, Xing Y. Predictive value of [18F]fluoro-2-deoxy-D-glucose positron emission tomography for clinical outcome in patients with relapsed/refractory diffuse large B-cell lymphoma prior to and after autologous stem cell transplant. Leuk Lymphoma. 2014;55(2):276–82. doi: 10.3109/10428194.2013.797974.
  25. Sucak GT, Ozkurt ZN, Suyani E, et al. Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival. Ann Hematol. 2011;90(11):1329–36. doi: 10.1007/s00277-011-1209-0.
  26. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008.
  27. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86. doi: 10.1200/jco.2006.09.2403.
  28. David G, Kleinbaum MK. Survival Analysis. A Self-Learning Text. 2nd edition. Springer; 2002. рр. 583. doi: 10.1111/j.1541-0420.2006.00540_18.x.
  29. Петрова Г.Д., Мелкова К.Н., Чернявская Т.З. и др. Первично-рефрактерное течение лимфомы Ходжкина и аутологичная трансплантация гемопоэтических стволовых клеток. Результаты одноцентрового проспективного исследования. Российский онкологический журнал. 2015;20(3):4–11.
    [Petrova GD, Melkova KN, Chernyavskaya TZ, et al. Primary refractory Hodgkin’s lymphoma and autologous stem cell transplantation: results of the single-center prospective study. Rossiiskii onkologicheskii zhurnal. 2015;20(3):4–11. (In Russ)]
  30. Crocchiolo R, Fallanca F, Giovacchini G, et al. Role of 18FDG-PET/CT in detecting relapse during follow-up of patients with Hodgkin’s lymphoma. Ann Hematol. 2009;88(12):1229–36. doi: 10.1007/s00277-009-0752-4.
  31. Gupta D, Lis ChG. Pretreatment Serum Albumin as a Predictor of Cancer Survival: A Systematic Review of the Epidemiological Literature. Nutrition J. 2010;9(1):69–116. doi: 10.1186/1475-2891-9-69.
  32. Демина Е.А. Лимфома Ходжкина: прогностические признаки сегодня. Современная онкология. 2006;4:4–7.
    [Demina EA. Hodgkin’s lymphoma: prognostic factors today. Sovremennaya onkologiya. 2006;4:4–7. (In Russ)]
  33. Czyz A, Lojko-Dankowska A, Dytfeld D, et al. Prognostic factors and long-term outcome of autologous haematopoietic stem cell transplantation following a uniform-modified BEAM-conditioning regimen for patients with refractory or relapsed Hodgkin lymphoma: a single-center experience. Med Oncol. 2013;30(3):611. doi: 10.1007/s12032-013-0611-y.
  34. Villa D, Seshadri T, Puig N, et al. Second-line salvage chemotherapy for transplant-eligible patients with Hodgkin’s lymphoma resistant to platinum-containing first-line salvage chemotherapy. Haematologica. 2012;97(5):751–7. doi: 10.3324/haematol.2011.047670.
  35. Colpo A, Hochberg E, Chen YB. Current status of autologous stem cell transplantation in relapsed and refractory Hodgkin’s lymphoma. Oncologist. 2012;17(1):80–90. doi: 10.1634/theoncologist.2011-0177.