Efficacy of donor lymphocyte infusion in patients after different types of allogeneic hematopoietic stem cell transplantation


Cite item

Full Text

Abstract

AIM: To evaluate the efficacy of donor lymphocyte infusion (DLI) to prevent and treat recurrences in patients after different types of allogeneic hematopoietic stem cell transplantation (allo-HSCT)/MATERIAL AND METHODS: Data from 118 patients with malignant blood diseases were analyzed. Allo-HSCTs from HLA-matched related donors (n=49), HLA-matched unrelated donors (n=50), partially HLA-matched unrelated donors (n=2), and haploidentical donors (n=24) were performed. The indications for DLI were underlying disease relapse (59 DLIs), resistant disease course (n=40), minimal residual disease (n=16), falling donor chimerism (n=15), and recurrence prevention (n=13)/RESULTS: Therapy response was obtained after 57 (44%) DLIs. There were 36 (25%) and 30 (21%) cases of acute and chronic graft-versus-host reactions (GVHR), respectively. The use of DLI from HLA-matched donors, its performance in the periods of D+100 to one year after allo-HSCT, a donor chimerism level of over 90% at the moment of DLI, the administration of the initial DLI dose of below 1·106 CD3+/kg, and the development of chronic GVHR after DLI were associated with the highest rate of therapy responses. The overall survival rates of patients with DLI were significantly influenced by factors, such as DLI periods, donor chimerism levels at DLI, and the development of chronic GVHR after DLI/CONCLUSION: The choice of the optimal dose of cells, the periods of DLI and its preventive administration improve prognosis in patients after allo-HSCT. The occurrence of acute GVHR is affected by the degree of HLA matching and the type of a donor. The development of chronic GVHR after DLI is associated with the highest rate of responses to DLI and higher survival rates.

Full Text

Эффективность инфузии донорских лимфоцитов у пациентов после различных видов аллогенной трансплантации гемопоэтических стволовых клеток. - Резюме. Цель исследования. Оценить эффективность инфузии донорских лимфоцитов (ИДЛ) с целью профилактики и лечения рецидивов у пациентов после различных видов аллогенной трансплантации гемопоэтических стволовых клеток (алло-ТГСК). Материалы и методы. Проанализированы данные 118 пациентов со злокачественными заболеваниями системы крови. Алло-ТГСК от совместимого по системе HLA родственного донора выполнены у 49, от совместимого неродственного - у 50, от частично совместимого неродственного - у 2, от гаплоидентичного донора - у 24 пациентов. Показаниями к ИДЛ были рецидив основного заболевания (59 ИДЛ), резистентное течение (40 ИДЛ), "минимальная остаточная болезнь" (16 ИДЛ), снижение донорского "химеризма" (15 ИДЛ) и профилактика рецидива (13 ИДЛ). Результаты. Ответ на терапию достигнут после 57 (44%) ИДЛ. Число случаев развития острой реакции трансплантат против хозяина (РТПХ) после ИДЛ составило 36 (25%), хронической РТПХ - 30 (21%). Использование ИДЛ от совместимого по системе HLA донора, проведение ИДЛ в сроки от Д+100 до 1 года после алло-ТГСК, уровень донорского "химеризма" на момент ИДЛ более 90%, использование начальной дозы ИДЛ менее 1·106 CD3+/кг, а также развитие хронической РТПХ после ИДЛ были ассоциированы с наибольшей частотой ответов на терапию. На уровни общей выживаемости ОВ пациентов с ИДЛ достоверно влияли такие факторы, как сроки проведения ИДЛ, уровень донорского "химеризма" на момент ИДЛ, а также развитие хронической РТПХ после ИДЛ. Заключение. Выбор оптимальной клеточной дозы, сроков проведения ИДЛ, а также проведение ИДЛ с превентивной и профилактической целью улучшают прогноз у пациентов после алло-ТГСК. На возникновение острой РТПХ после ИДЛ влияют степень совместимости по системе HLA и тип донора. Развитие хронической РТПХ после ИДЛ ассоциировано с наибольшей частотой ответов на ИДЛ и более высокой общей выживаемостью.
×

References

  1. Афанасьев Б. В., Зубаровская Л. С., Семенова Е. В. и др. Опыт применения неродственной аллогенной трансплантации стволовых гемопоэтических клеток в клинике трансплантации костного мозга СПбГМУ им. акад. И.П. Павлова. Тер арх 2007; 7: 35-42.
  2. Зубаровская Л.С., Семенова Е.В., Алянский А.Л., Афанасьев Б.В. Особенности трансплантации гемопоэтических стволовых клеток у детей. Метод. пос. для врачей. СПб 2009.
  3. Мелкова К.Н., Пушкарева С.Г. Использование трансплантации гемопоэтических стволовых клеток при острых лейкозах: материалы 37-го конгресса Европейского общества по трансплантации костного мозга (EBMT). Клин онкогематол 2011; 2: 178-180.
  4. Менделеева Л.П., Савченко В.Г., Любимова Л.С. и др. Трансплантация гемопоэтических клеток в Российской Федерации (отчет Межрегионального регистра за 1996-2006 гг.). Гематол и трансфузиол 2007; 6: 31-36.
  5. Румянцев А.Г., Масчан А.А. Трансплантация гемопоэтических стволовых клеток у детей. Руководство для врачей. М: Медицинское информационное агентство 2003.
  6. Савченко В.Г., Любимова Л.С., Паровичникова Е.Н. и др. Трансплантация аллогенных и аутологичных гемопоэтических стволовых клеток при острых лейкозах (итоги 20-летнего опыта) Тер арх 2007; 7: 30-35.
  7. Soiffer J.R. Stem Cell Transplantation for Hematologic Malignancies. Totowa, New Jersey: Humana Press 2004.
  8. Thomas E.D., Storb R., Clift R.A. et al. Bone marrow transplantation. N Engl J Med 1975; 292: 832-843.
  9. Giralt S.A., Champlin R.E. Recurrence of the underlying malignant disease. In: Atkinson K (ed.). Clinical Bone Marrow and Blood Stem Cell Transplantation. 2nd ed. Cambridge: Cambridge University Press; 2000: 878-888.
  10. Goldman J.M., Majhail N.S., Klein J.P. et al. Relapse and late mortality in 5-year survivors of myeloablative allogeneic hematopoietic cell transplantation for chronic myeloid leukemia in first chronic phase. J Clin Oncol 2010; 28 (11): 1888-1895.
  11. Porter D.L., Levine J.E. Graft-versus-host disease and graft-versus-leukemia after donor leukocyte infusion. Seminars in Hematol 2006; 43 (1): 53-61.
  12. Van den Brink M.R.M., Porter D.L., Giralt S. Relapse after Allogeneic Hematopoietic Cell Therapy. Biol Blood Marrow Transplant 2010; 16: 138-145.
  13. Shaw B.E., Russell N.H. Treatment options for the management of acute leukemia relapsing following an allogeneic transplant. Bone Marrow Transplant 2008; 41: 495-503.
  14. Formankova R., Sedlacek P., Keslova P. et al. Adoptive immunotherapy, chemotherapy, and second allogeneic transplant in the treatment of post-transplant relapse of acute leukemia in children: a single center experience. Leuk Lymphoma 2010; 51 (10): 1936-1940.
  15. Kroger N. Approaches to relapse after allogeneic stem cell transplantation. Cur Opin Oncol 2011; 23: 203-208.
  16. Kolb H.J. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood 2008; 112: 4371-4383.
  17. Deol A., Lum L.G. Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treat Rev 2010; 36 (7): 528-538.
  18. Collins J.R.H., Goldstein S., Giralt S. et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant 2000; 26: 511-516.
  19. Dazzi F., Szydlo R.M., Apperley J.F., Goldman J.M. Prognostic factors for acute graft-versus-host disease after donor lymphocyte infusions. Blood 2002; 100 (7): 2673-2674.
  20. Huff C.A., Fuchs E.J., Smith B.D. et al. Graft-versus-host reactions and the effectiveness of donor lymphocyte infusions. Biol Blood Marrow Transplant 2006; 12: 414-421.
  21. Marks D.I., Lush R., Cavenagh J. et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2002; 100: 3108-3114.
  22. Raiola A., Van Lint M., Valbonesi M. et al. Factors predicting response and graftversus-host disease after donor lymphocyte infusions: a study on 593 infusions. Bone Marrow Transplant 2003; 31: 687.
  23. Rettinger E., Willasch A.M., Kreyenberg H. et al. Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing evidence of mixed chimerism after allogeneic stem cell transplantation. Blood 2011; 118 (20): 5681-5688.
  24. Candoni A., Tiribelli M., Toffoletti E. et al. Quantitative assessment of WT1gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemia. Eur J Haematol 2009; 82 (1): 61-68.
  25. Желнова Е. И., Менделеева Л.П., Любимова Л.С. и др. Эффективность терапии лимфоцитами донора и интерлейкином-2 у пациента с двумя посттрансплантационными рецидивами острого миелоидного лейкоза. Тер арх 2007; 8: 67-69.
  26. Inamoto Y., Fefer A., Sandmaier B.M. et al. A Phase I/II Study of Chemotherapy Followed by Donor Lymphocyte Infusion plus Interleukin-2 for Relapsed Acute Leukemia after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2011; 17: 1308-1315.
  27. Posthuma E.F.M., Marijt E.W.A.F., Barge R.M.Y. et al. α-Interferon with Very-Low-Dose Donor Lymphocyte Infusion for Hematologic or Cytogenetic Relapse of Chronic Myeloid Leukemia Induces Rapid and Durable Complete Remissions and Is Associated with Acceptable Graft-versus-Host Disease. Biol Blood Marrow Transplant 2004; 10: 204-212.
  28. Choi S.J., Lee J.H., Lee J.H. et al. Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a prospective study. Bone Marrow Transplant 2005; 36: 163-169.
  29. Levine J., Braun T., Penza S. et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem cell transplantation. J Clin Oncol 2002; 20: 405-412.
  30. Bavaro P., Pompetti F., Olioso P. et al. Response to combined use of donor lymphocyte infusions and imatinib mesylate in patients relapsed after allogeneic stem cell transplantation for chronic myeloid leukemia. 13th Congress of the European Hematology Association. Haematologica 2008; 93 (137): 0337.
  31. Tiribelli M., Sperotto A., Candoni A. et al. Nilotinib and donor lymphocyte infusion in the treatment of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation and resistant to imatinib. Leukemia Res 2009; 33: 174-177.
  32. Lubbert M., Bertz H., Wasch R. Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting. Bone Marrow Transplant 2010; 45: 627-632.
  33. Bloor A.J.C., Thomson K., Chowdhry N. et al. High response rate to donor lymphocyte infusion after allogeneic stem cell transplantation for indolent non-Hodgkin lymphoma. Biol Blood Marrow Transplant 2008; 14: 50-58.
  34. Klyuchnikov E., Sputtek A., Slesarchuk O. et al. Purification of CD4+ T cells for adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2011; 17 (3): 374-383.
  35. Huang X.J., Wang Y., Liu D.H. et al. Administration of short-term immunosuppressive agents after DLI reduces the incidence of DLI-associated acute GVHD without influencing the GVL effect. Bone Marrow Transplant 2009; 44: 309-316.
  36. Dazzi F., Szydlo R.M., Craddock C. et al. Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood 2000; 95: 67-71.
  37. Guglielmi C., Arcese W., Dazzi F. et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood 2002; 100: 397-405.
  38. Lewalle P., Triffet A., Delforge A. et al. Donor lymphocyte infusions in adult haploidentical transplant: a dose finding study. Bone Marrow Transplant 2003; 31: 39-44.
  39. Simula M.P., Marktel S., Fozza C. et al. Response to donor lymphocyte infusions for chronic myeloid leukemia is dose-dependent: the importance of escalating the cell dose to maximize therapeutic efficacy. Leukemia 2007; 21: 943-948.
  40. Vela-Ojeda J., Garcia-Ruiz Esparza M.A., Reyes-Maldonado E. et al. Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: prognostic significance of the dose of CD3+ and CD4+ lymphocytes. Ann Hematol 2004; 83: 295-301.
  41. Schmid C., Labopin M., Nagler A. et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol 2007; 25: 4938-4945.
  42. Montero A., Savani B.N., Shenoy A. et al. T-cell depleted peripheral blood stem cell allotransplantation with T cell add back for patients with hematological malignancies: effect of chronic GVHD on outcome. Biol Blood Marrow Transplant 2006; 12: 1318-1325.
  43. Peggs K.S., Thomson K., Hart D.P. et al. Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses. Blood 2004; 103: 1548-1556.
  44. Maruyama D., Fukuda T., Kato R. et al. Comparable antileukemia/ lymphoma effects in nonremission patients undergoing allogeneic hematopoietic cell transplantation with a conventional cytoreductive or reduced-intensity regimen. Biol Blood Marrow Transplant 2007; 13: 932-941.
  45. Huff C.A., Fuchs E.J., Smith B.D. et al. Graft-versus-host reactions and the effectiveness of donor lymphocyte infusions. Biol Blood Marrow Transplant 2006; 12: 414-421.
  46. Or R., Hadar E., Bitan M. et al. Safety and efficacy of donor lymphocyte infusions following mismatched stem cell transplantation. Biol Blood Marrow Transplant 2006; 12: 1295-1301.
  47. Rizzieri D.A., Dev P., Long G.D. et al. Response and toxicity of donor lymphocyte infusions following T-cell depleted non-myeloablative allogeneic hematopoietic SCT from 3-6/6 HLA matched donors. Bone Marrow Transplant 2009; 43: 327-333.
  48. Lewalle P., Triffet A., Delforge A. et al. Donor lymphocyte infusions in adult haploidentical transplant: a dose finding study. Bone Marrow Transplant 2003; 31: 39-44.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2013 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

 © 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies