Allogeneic hematopoietic stem cell transplantation in patients with multiple myeloma
- Authors: Firsova M.V.1, Mendeleeva L.P.1, Parovichnikova E.N.1, Solovev M.V.1, Kuzmina L.A.1, Risinskaya N.V.1, Abramova T.V.1, Galtseva I.V.1, Savchenko V.G.1
-
Affiliations:
- National Research Center for Hematology
- Issue: Vol 93, No 7 (2021)
- Pages: 778-784
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/76313
- DOI: https://doi.org/10.26442/00403660.2021.07.200929
- ID: 76313
Cite item
Full Text
Abstract
Aim. To analyze the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a related HLA-identical donor in patients with multiple myeloma (MM).
Materials and methods. From 2013 to 2018, the study included 8 patients (6 men, 2 women) aged from 27 to 55 years (median 39 years) with MM who underwent allo-HSCT from a related HLA-identical donor (7 patients – after auto-HSCT, in 1 case – without previous auto-transplantation). All patients required 2 or more lines of induction therapy, while the achieved antitumor effect was unstable. Before allo-HSCT, complete and very good partial remission was determined in isolated cases, in 4 patients the response was regarded as partial remission, stabilization – in 1 observation, progression – in 1 patient. All patients underwent reduced intensity conditioning (fludarabine 30 mg/m2 × 6 days + busulfan 4 mg/kg × 2 days). Immunosuppressive therapy included the administration of antithymocyte globulin and post-transplant cyclophosphamide.
Results. Severe acute GVHD (grade 3–4) was observed in 3 (37.5%) cases, which resulted in death in 1 case. A stable antitumor response was achieved in 5 (62.5%) patients, complete remission lasts for 29–86 months after allo-HSCT. Specific therapy for these patients is not carried out. The 7-year progression-free survival rate was 75%, the 7-year overall survival rate was 84%, with a median follow-up of 65 months. The transplant-related mortality was 12.5%.
Conclusion. Allo-HSCT is considered as an alternative method of therapy for young patients with aggressive MM. Allo-HSCT in MM in some cases leads to long-term immunological control of the tumor.
Full Text
##article.viewOnOriginalSite##About the authors
Maiia V. Firsova
National Research Center for Hematology
Author for correspondence.
Email: firs-maia@yandex.ru
ORCID iD: 0000-0003-4142-171X
канд. мед. наук, ст. науч. сотр. отд-ния интенсивной высокодозной химиотерапии парапротеинемических гемобластозов
Russian Federation, MoscowLarisa P. Mendeleeva
National Research Center for Hematology
Email: firs-maia@yandex.ru
ORCID iD: 0000-0002-4966-8146
д-р мед. наук, проф., рук. управления по научной и образовательной работе, зав. отд. химиотерапии парапротеинемических гемобластозов
Russian Federation, MoscowElena N. Parovichnikova
National Research Center for Hematology
Email: firs-maia@yandex.ru
ORCID iD: 0000-0001-6177-3566
д-р мед. наук, рук. отд. химиотерапии гемобластозов, депрессий кроветворения и ТКМ
Russian Federation, MoscowMaksim V. Solovev
National Research Center for Hematology
Email: firs-maia@yandex.ru
ORCID iD: 0000-0002-7944-6202
канд. мед. наук, зав. отд-нием интенсивной высокодозной химиотерапии парапротеинемических гемобластозов
Russian Federation, MoscowLarisa A. Kuzmina
National Research Center for Hematology
Email: firs-maia@yandex.ru
ORCID iD: 0000-0001-6201-6276
канд. мед. наук, зав. отд-нием интенсивной высокодозной химиотерапии и трансплантации костного мозга с круглосуточным и дневным стационарами
Russian Federation, MoscowNatalia V. Risinskaya
National Research Center for Hematology
Email: firs-maia@yandex.ru
ORCID iD: 0000-0003-2957-1619
канд. биол. наук, ст. науч. сотр. лаб. молекулярной гематологии
Russian Federation, MoscowTatiana V. Abramova
National Research Center for Hematology
Email: firs-maia@yandex.ru
ORCID iD: 0000-0003-3163-4930
канд. мед. наук, врач КЛД лаб. кариологии
Russian Federation, MoscowIrina V. Galtseva
National Research Center for Hematology
Email: firs-maia@yandex.ru
ORCID iD: 0000-0002-8490-6066
канд. мед. наук, зав. лаб. иммунофенотипирования клеток крови и костного мозга
Russian Federation, MoscowValerii G. Savchenko
National Research Center for Hematology
Email: firs-maia@yandex.ru
ORCID iD: 0000-0001-8188-5557
акад. РАН, д-р мед. наук, проф., ген. дир.
Russian Federation, MoscowReferences
- Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122-8. doi: 10.1038/leu.2013.313
- Dhakal B, Szabo A, Chhabra S, et al. Autologous Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Novel Agent Induction: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4(3):343-50. doi: 10.1001/jamaoncol.2017.4600
- Lokhorst HM, Segeren CM, Verdonck LF, et al. Dutch-Belgian Hemato-Oncology Cooperative Group. Partially T-cell-depleted allogeneic stem-cell transplantation for first-line treatment of multiple myeloma: a prospective evaluation of patients treated in the phase III study HOVON 24 MM. J Clin Oncol. 2003;21(9):1728-33. doi: 10.1200/JCO.2003.04.033
- Gahrton G, Tura S, Ljungman P, et al. Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma. J Clin Oncol. 1995;13(6):1312-22. doi: 10.1200/JCO.1995.13.6.1312
- Bensinger WI, Buckner CD, Anasetti C, et al. Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome. Blood. 1996;88(7):2787-93
- Crawley C, Iacobelli S, Björkstrand B, et al. Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning. Blood. 2007;109(8):3588-94. doi: 10.1182/blood-2006-07-036848
- Lokhorst H, Einsele H, Vesole D, et al. International Myeloma Working Group. International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma. J Clin Oncol. 2010;28(29):4521-30. doi: 10.1200/JCO.2010.29.7929
- Krishnan A, Pasquini MC, Logan B, et al. Blood Marrow Transplant Clinical Trials Network (BMT CTN). Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011;12(13):1195-203. doi: 10.1016/S1470-2045(11)70243-1
- Giaccone L, Storer B, Patriarca F, et al. Long-term follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma. Blood. 2011;117(24):6721-7. doi: 10.1182/blood-2011-03-339945
- Moreau P, Garban F, Attal M, et al. IFM Group. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood. 2008;112(9):3914-5. doi: 10.1182/blood-2008-07-168823
- Gahrton G, Iacobelli S, Björkstrand B, et al. EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013;121(25):5055-63. doi: 10.1182/blood-2012-11-469452
- Rosiñol L, Pérez-Simón JA, Sureda A, et al. Programa para el Estudio y la Terapéutica de las Hemopatías Malignas y Grupo Español de Mieloma (PETHEMA/GEM). A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma. Blood. 2008;112(9):3591-3. doi: 10.1182/blood-2008-02-141598
- Armeson KE, Hill EG, Costa LJ. Tandem autologous vs autologous plus reduced intensity allogeneic transplantation in the upfront management of multiple myeloma: meta-analysis of trials with biological assignment. Bone Marrow Transplant. 2013;48(4):562-7. doi: 10.1038/bmt.2012.173
- Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-48. doi: 10.1016/S1470-2045(14)70442-5
- Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328-46. doi: 10.1016/S1470-2045(16)30206-6
- Sobh M, Michallet M, Gahrton G, et al. Allogeneic hematopoietic cell transplantation for multiple myeloma in Europe: trends and outcomes over 25 years. A study by the EBMT Chronic Malignancies Working Party. Leukemia. 2016;30(10):2047-54. doi: 10.1038/leu.2016.101
- Greil C, Engelhardt M, Ihorst G, et al. Allogeneic transplantation of multiple myeloma patients may allow long-term survival in carefully selected patients with acceptable toxicity and preserved quality of life. Haematologica. 2019;104(2):370-9. doi: 10.3324/haematol.2018.200881
- Bruno B, Rotta M, Patriarca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007;356(11):1110-20. doi: 10.1056/NEJMoa065464
- Garban F, Attal M, Michallet M, et al. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006;107(9):3474-80. doi: 10.1182/blood-2005-09-3869
- Gonsalves WI, Buadi FK, Ailawadhi S, et al. Utilization of hematopoietic stem cell transplantation for the treatment of multiple myeloma: a Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus statement. Bone Marrow Transplant. 2019;54(3):353-67. doi: 10.1038/s41409-018-0264-8
- Duarte RF, Labopin M, Bader P, et al. European Society for Blood and Marrow Transplantation (EBMT). Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transplant. 2019;54(10):1525-52. doi: 10.1038/s41409-019-0516-2
- Паровичникова Е.Н., Васильева В.А., Довыденко М.В. и др. Протоколы трансплантации аллогенных гемопоэтических стволовых клеток. М.. 2020; c. 218-24 [Parovichnikova EN, Vasileva VA, Dovydenko MV, et al. Allogeneic Hematopoietic Stem Cell Transplant Protocols. Moscow, 2020; p. 218-24 (in Russian)]
Supplementary files
![](/img/style/loading.gif)