ASU FERGÜN YILMAZ, Ayhan DÖNMEZ, Ajda GÜNEŞ, MURAT TOMBULOĞLU

Autologous stem cell transplantation as a consolidation therapy in acute myeloid leukemia patients

Amaç: Akut myelositer lösemi (AML) olgularında remisyon sonrası konsolidasyon tedavisi olarak otolog hematopoetik kök hücre nakli (OHKHN) seçenekler arasında güncelliğini korumaktadır. Yapılan çalışmalarda, yüksek doz ara-C (YDAC) tedavisi ile karşılaştırıldığında, OHKHN nin total sağkalımı etkilemediği halde hastalıksız sağkalımı arttırabileceği gösterilmiştir. Özellikle yeni gelişmelerle nakil sonrası mortalite ve morbiditenin azalması ile OHKHN nin önemi artmıştır. Çalışmamızda, remisyon sağlanmasını takiben YDAC uygulaması sonrası OHKHN gerçekleştirilen hastaların sonuçları değerlendirilmiştir. Gereç ve Yöntem: 1998-2012 yılları arasında tanı alan tüm AML hastaları retrosprktif olarak incelendi. İndüksiyon kemoterapisi ile remisyon elde edildikten sonra YDAC (3 gr/m2 /gün, gün aşırı, 3 gün) konsolidasyonu uygulamasını takiben OHKHN uygulanan 23 AML hastası çalışmaya dahil edildi. İstatistik değerlendirmeler ve sağkalım hesaplamaları Graphpad 4.03 yazılımı ile yapılmış, sonuçlar ortanca (alt-üst sınır) olarak sunuldu. Bulgular: Hastaların nötrofil ve trombosit yamanma süreleri median değerleri sırasıyla 12 (8-28) gün ve 14 (8-100) gün olarak bulundu. Nakil ilişkili ölüm izlenmezken nakil sonrası nüks eden 15 hastanın 13ü refrakter hastalık nedeniyle kaybedildi. Ortanca 40 (6-144) aylık izlemde; ortanca total ve hastalıksız yaşam süreleri sırasıyla 48 ve 34 ay olup, 144. ayda total sağkalım oranı % 32.2 ve 130. ayda hastalıksız sağkalım oranı % 27.3 olarak bulundu. Sonuç: Birinci kür indüksiyon kemoterapisi ile tam remisyon sağlanan hastalarda YDAC uygulamasını takiben OHKHN uygulaması uzun süreli hastalıksız yaşam sağlayabilir. Özellikle uyumlu verici bulunamayan hastalarda YDAC pekiştirme tedavisinin ardından otolog nakil uygun bir seçenek olarak akılda tutulmalıdır.

Akut myelositer lösemi hastalarında konsolidasyon tedavisi olarak otolog hematopoetik kök hücre nakli uygulaması

Aim: Autologous stem cell transplantation (ASCT) is a treatment option as a consolidation therapy in acute myeloid leukemia (AML) patients. ASCT may improve disease free survival without effecting overall survival rates when compared with high dose Ara-C (HDARAC). ASCT becomes even more important after mortality and morbidity rates decrease with the new improvements. In this study, we analyzed the results of patients treated with ASCT after HDARAC therapy in the first remission. Materials and Methods: AML patients diagnosed between 1998 and 2012 were retrospectively analyzed. After remission achieved by induction therapy and HDARAC consolidation therapy (3 gr/m2 , on alternate 3 days) 23 patients who were treated with ASCT were enrolled in the study. Statistical analysis and survival rates were analyzed by Graphpad 4.03 and the results were reported as median (range, minimum-maximum). Results: The median time to neutrophil and thrombocyte engraftments was 12 (range, 828) days and 14 (8100) days, respectively. We did not document any transplantation related mortality. Fifteen patients relapsed after ASCT and 13 of them died due to refractory disease. The median follow up period was 40 (range, 6-144) months. The median overall survival and disease free survival were 48 and 34 months, respectively. The overall survival rate was 32.2% at 144th month and the disease free survival rate was 27.3 % at 130th month. Conclusion: ASCT may provide a long term disease free survival in AML patients after one cycle of induction chemotherapy and HDARAC as a consolidation therapy. Especially in AML patients without suitable related or unrelated donors, ASCT may provide a treatment option.

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1. Ferrara F. Renaissance of autologous stem cell transplantation for AML? Lancet Oncol 2012;13(2):121-3. 2. Canzoniero JV, Bhatnagar B, Baer MR, Gojo I. Upfront therapy of acute myeloid leukemia. Curr Oncol Rep 2011;13(5):361-70. 3. Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115(3):453-7. 4. Jung AS, Holman PR, Castro JE, et al. Autologous hematopoietic stem cell transplantation as an intensive consolidation therapy for adult patients in remission from acute myelogenous leukemia. Biol Blood Marrow Transplant 2009;15(10):1306-13. 5. Brenner MK, Rill DR, Holladay MS, et al. Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patients. Lancet 1993;342(8880):1134-7. 6. Brenner MK, Rill DR, Moen RC, et al. Gene-marking to trace origin of relapse after autologous bone-marrow transplantation. Lancet 1993;341(8837):85-6. 7. Yanada M, Matsuo K, Emi N, Naoe T. Efficacy of allogeneic hematopoietic stem cell transplantation depends on cytogenetic risk for acute myeloid leukemia in first disease remission: A metaanalysis. Cancer 2005;103(8):1652-8. 8. Nathan PC, Sung L, Crump M, Beyene J. Consolidation therapy with autologous bone marrow transplantation in adults with acute myeloid leukemia: a meta-analysis. J Natl Cancer Inst 2004;96(1):38-45. 9. Levi I, Grotto I, Yerushalmi R, Ben-Bassat I, Shpilberg O. Meta-analysis of autologous bone marrow transplantation versus chemotherapy in adult patients with acute myeloid leukemia in first remission. Leuk Res 2004;28(6):605-12. 10. Breems DA, Lowenberg B. Autologous stem cell transplantation in the treatment of adults with acute myeloid leukaemia. Br J Haematol 2005;130(6):825-33. 11. Jing Y, Li H, Zhao Y, et al. Efficacy of allogeneic and autologous hematopoietic SCT in patients with AML after first complete remission. Bone Marrow Transplant 2013;48(3):383-9. 12. Wrench D, Gribben JG. Stem cell transplantation for non-Hodgkin's lymphoma. Hematol Oncol Clin North Am 2008; 22(5):1051-79. 13. Giralt S. Stem cell transplantation for multiple myeloma: Current and future status. Hematology Am Soc Hematol Educ Program 2011;2011:191-6. 14. Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy sensitive non-Hodgkinslymphoma. N Engl J Med 1995;333(23):540-5. 15. Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkins disease: A randomised trial. Lancet 2002; 359(9323):2065-71. 16. Child JA, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003;348(19):1875-83. 17. Eto T, Takase K, Miyamoto T, et al. Autologous peripheral blood stem cell transplantation with granulocyte colony-stimulating factor combined conditioning regimen as a postremission therapy for acute myelogenous leukemia in first complete remission. Int J Hematol 2013;98(2):186-96. 18. Vellenga E, van Putten W, Ossenkoppele GJ, et al. Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); Swiss Group for Clinical Cancer Research Collaborative Group (SAKK). Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood 2011;118(23):6037-42. 19. Sabty FA, Demeckova E, Bojtarova E, Hrubisko M, Mistrik M. Is there still a role for autologous stem cell transplantation in acute myeloid leukemia? Neoplasma 2013;60(2):167-73. 20. Guièze R, Cornillet-Lefebvre P, Lioure B, et al. Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3-ITD molecular status for cytogenetically normal AML patients: A GOELAMS study. Am J Hematol 2012;87(12):1052-6. 21. Jourdan E, Rigal-Huguet F, Marit G, et al. BGMT Study Group. One versus two high-dose cytarabine-based consolidation before autologous stem cell transplantation for young acute myeloblastic leukaemia patients in first complete remission. Br J Haematol 2005;129(3):403-10. 22. Michallet AS, Chelghoum Y, Thiebaut A, et al. Autologous hematopoietic stem cell transplantation for adults with acute myeloid leukemia in complete remission: the Edouard Herriot Hospital experience. Hematology 2006;11(3):157-64. 23. Fernandez HF, Sun Z, Litzow MR, et al. Autologous transplantation gives encouraging results for young adults with favorable- risk acute myeloid leukemia, but is not improved with gemtuzumab ozogamicin. Blood 2011;117(20):5306-13. 24. Reiffers J, Labopin M, Sanz M, et al. Autologous blood cell vs marrow transplantation for acute myeloid leukemia in complete remission: An EBMT retrospective analysis. Bone Marrow Transplant 2000;25(11):1115-9. 25. Mehta J, Powles R, Singhal S, Treleaven J. Peripheral blood stem cell transplantation may result in increased relapse of acute myeloid leukaemia due to reinfusion of a higher number of malignant cells. Bone Marrow Transplant 1995;15(4):652-3. 26. Gorin NC. Autologous stem cell transplantation in acute myelocytic leukemia. Blood 1998;92(4):1073-90. 27. Zittoun RA, Mandelli F, Willemze R, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med 1995;332(4):217-23. 28. Tsimberidou AM, Stavroyianni N, Viniou N, et al. Hellenic Cooperative Group. Comparison of allogeneic stem cell transplantation, high-dose cytarabine, and autologous peripheral stem cell transplantation as postremission treatment in patients with de novo acute myelogenous leukemia. Cancer 2003;97(7):1721-31. 29. Burnett AK, Goldstone AH, Stevens RM, et al. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: Results of MRC AML 10 trial. UK Medical Research Council Adult and Children's Leukaemia Working Parties. Lancet 1998;351(9104):700-8. 30. von Grünigen I, Raschle J, Rüsges-Wolter I, Taleghani BM, Mueller BU, Pabst T. The relapse risk of AML patients undergoing autologous transplantation correlates with the stem cell mobilizing potential. Leuk Res 2012;36(11):1325-9. 31. Wang J, Ouyang J, Zhou R, Chen B, Yang Y. Autologous hematopoietic stem cell transplantation for acute myeloid leukemia in first complete remission: A meta-analysis of randomized trials. Acta Haematol 2010;124(2):61-71.