Survival of Patients with Acute Myeloid Leukemia after Allogeneic Stem Cell Transplantation: An Experience in Developing Country
Background: Allogeneic stem cell transplantation (allo-SCT) is the highest potential treatment for long-term survival as post-remission therapy for acute myeloid leukemia (AML). The aim of this study was to estimate the overall survival (OS) of patients with AML after allo-SCT and to identify the factors affecting them as a prognostic factor for the survival of patients.
Material and methods: In this retrospective cohort study, data of patients with AML who underwent allo-SCT at Taleghani bone marrow transplantation and cell therapy center in Tehran, Iran, from May 2009 to September 2016 were used. A total of 101 patients were enrolled and death time was considered a failure event for them. Kaplan-Meier method, log-Rank tests, and Cox proportional hazard model were used to evaluate OS and to identify the risk factors of patient’s survival. The SPSS software version 21 was used for the analysis of data and P<0.05 was considered a significant level.
Results: Of 101 patients with AML, 49 (48.5%) were males. The median age at allo-SCT was 32.76 years and 42 patients (41.6%) died. The 5-year OS and disease-free survival (DFS) was 56% (95%CI: 51-61%) and 52% (95%CI: 57-47%), respectively. Multivariate analysis by Cox regression indicated that OS has a significant relationship with WBC count and relapse (P=0.001).
Conclusion: Our results showed that allo–SCT has nearly the same outcome in developing countries and the WBC count and relapse are effective factors on the chance of survival in AML patients after allo-SCT.
2. Gyurkocza B, Storb R, Storer BE, et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010;28(17):2859-67.
3. Khwaja A, Bjorkholm M, Gale RE, et al. Acute myeloid leukaemia. Nat Rev Dis Primers . 2016;2:16010.
4. Ming Yi , Anping Li , Linghui Zhou , et al.The global burden and attributable risk factor analysis of acute myeloid leukemia in 195 countries and territories from 1990 to 2017: estimates based on the global burden of disease study 2017. J Hematol Oncol. 2020;13(1):72.
5. De Kouchkovsky I, Abdul-Hay M. 'Acute myeloid leukemia: a comprehensive review and 2016 update'. Blood Cancer J. 2016;6(7):e441.
6. Rautenberg C, Germing U, Haas R, et al. Relapse of Acute Myeloid Leukemia after Allogeneic Stem Cell Transplantation: Prevention, Detection, and Treatment. Int J Mol Sci. 2019;20(1):228.
7. Lee CJ, Savani BN, Mohty M, et al. Post-remission strategies for the prevention of relapse following allogeneic hematopoietic cell transplantation for high-risk acute myeloid leukemia: expert review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2019;54(4):519-530.
8 Schlenk RF. Post-remission therapy for acute myeloid leukemia. Haematologica. 2014;99(11):1663-70.
9. Burnett AK. Optimal induction and post-remission therapy for acute myeloid leukemia. Leuk Suppl . 2012;1(Suppl 2):S14-5.
10. Sanders MA, Valk PJ. The evolving molecular genetic landscape in acute myeloid leukaemia. Curr Opin Hematol . 2013;20(2):79-85.
11 Gupta M, Mahapatra M, Saxena R. Cytogenetics' impact on the prognosis of acute myeloid leukemia. J Lab Physicians . 2019;11(2):133-137.
12. Imai Y. [AML treatment strategy based on cytogenetic abnormalities and somatic mutations]. [Rinsho ketsueki]. Rinsho Ketsueki. 2015;56(10):1932-41.
13. Lagunas-Rangel FA, Chavez-Valencia V, Gomez-Guijosa MA, et al. Acute Myeloid Leukemia-Genetic Alterations and Their Clinical Prognosis. Int J Hematol Oncol Stem Cell Res . 2017;11(4):328-339.
14. Kumar CC. Genetic abnormalities and challenges in the treatment of acute myeloid leukemia. Genes Cancer . 2011;2(2):95-107.
15. Othus M, Appelbaum FR, Petersdorf SH, et al. Fate of patients with newly diagnosed acute myeloid leukemia who fail primary induction therapy. B Biol Blood Marrow Transplant. 2015;21(3):559-64.
16. Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.
17. Kolb E Anders, Pooja Gidwani, Stephan A Grupp. Hematopoietic Stem Cell Transplantation. eMedicine Specialties 2006; Pediatrics: General Medicine, Oncology.
18. Bejanyan N, Oran B, Shanley R, et al. Clinical outcomes of AML patients relapsing after matched-related donor and umbilical cord blood transplantation. Bone Marrow Transplant. 2014;49(8):1029-35.
19. Yang X, Wang J. Precision therapy for acute myeloid leukemia. J Hematol Oncol . 2018;11(1):3.
20. Rowe JM. Optimal induction and post-remission therapy for AML in first remission. Hematology Am Soc Hematol Educ Program. 2009;396-405.
21 Cornelissen JJ, Gratwohl A, Schlenk RF, et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol . 2012;9(10):579-90.
22. Koreth J, Schlenk R, Kopecky KJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009;301(22):2349-61.
23. de Lima M, Porter DL, Battiwalla M, et al. Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse After Hematopoietic Stem Cell Transplantation: part III. Prevention and treatment of relapse after allogeneic transplantation. Biology of blood and marrow transplantation. Biol Blood Marrow Transplant . 2014;20(1):4-13.
24. Alyea EP, DeAngelo DJ, Moldrem J, et al. NCI First International Workshop on The Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: report from the committee on prevention of relapse following allogeneic cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant . 2010;16(8):1037-69.
25. Stelljes M, Krug U, Beelen DW, et al. Allogeneic transplantation versus chemotherapy as postremission therapy for acute myeloid leukemia: a prospective matched pairs analysis. J Clin Oncol. 2014;32(4):288-96.
26. Smith ML, Hills RK, Grimwade D. Independent prognostic variables in acute myeloid leukaemia. Blood Rev. 2011;25(1):39-51.
27. Bornhauser M, Kienast J, Trenschel R, et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012;13(10):1035-44.
28. Fasslrinner F, Schetelig J, Burchert A, et al. Long-term efficacy of reduced-intensity versus myeloablative conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: retrospective follow-up of an open-label, randomised phase 3 trial. Lancet Haematol . 2018;5(4):e161-e169.
29. Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003;21(24):4642-9.
30. Dohner 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):453-74.
31. Mitus AJ, Miller KB, Schenkein DP, et al. Improved survival for patients with acute myelogenous leukemia. J Clin Oncol . 1995;13(3):560-9.
32. Baron F, Labopin M, Niederwieser D, et al. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation. Leukemia 2012;26(12):2462-8.
33. Frazer J, Couban S, Doucette S, et al. Characteristics predicting outcomes of allogeneic stem-cell transplantation in relapsed acute myelogenous leukemia. Curr Oncol. 2017;24(2):e123-e130.
34. Akbarzadeh Baghban A, hosseinifard H, Baghestani A R, et al. Factors that affecting survival of patients with acute myeloid leukemia. Koomesh. 2016;17(3):596-602.
35. Safar A, Rahgozar M, Shahei F, et al. Survival analysis of acute myeloid leukemia.RJMS. 2015; 22 (134) :41-48.
36. Gupta V, Tallman MS, Weisdorf DJ. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood. 2011;117(8):2307-18.
37. Ganapule A, Nemani S, Korula A, et al. Allogeneic Stem Cell Transplant for Acute Myeloid Leukemia: Evolution of an Effective Strategy in India. J Glob Oncol. 2017;3(6):773-781.
38. Michelis FV, Atenafu EG, Gupta V, et al. Duration of first remission, hematopoietic cell transplantation-specific comorbidity index and patient age predict survival of patients with AML transplanted in second CR. Bone Marrow Transplant. 2013;48(11):1450-5.
39. Lee S, Tallman MS, Oken MM, et al. Duration of second complete remission compared with first complete remission in patients with acute myeloid leukemia. Eastern Cooperative Oncology Group. Leukemia. 2000;14(8):1345-8.
40. Sayehmiri K, Almasi E, Sarokhani D, et al. Prognostic factors for survival in acute leukemia patients after bone marrow transportation using Semi-Markov multi-state models in Tehran Shariati Hospital Research in Medicine. 2013;36(5):83-7.
41. Bejanyan N, Weisdorf DJ, Logan BR, et al. Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. Biol Blood Marrow Transplant . 2015;21(3):454-9.
42. de Jonge HJ, Valk PJ, de Bont ES, Schuringa JJ, Ossenkoppele G, Vellenga E, et al. Prognostic impact of white blood cell count in intermediate risk acute myeloid leukemia: relevance of mutated NPM1 and FLT3-ITD. Haematologica. 2011;96(9):1310-7.
43. Padilha SL, Souza EJ, Matos MC, et al. Acute myeloid leukemia: survival analysis of patients at a university hospital of Parana. Rev Bras Hematol Hemoter. 2015;37(1):21-7.
44. Su L, Li W, Cui JW, et al. [Correlation of NPM1, FLT3-ITD mutations with leukocyte count and myeloblasts percentage in AML patients with normal karyotype]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013;21(3):571-5.
45.van Buchem MA, te Velde J, Willemze R, et al. Leucostasis, an underestimated cause of death in leukaemia. Blut. 1988;56(1):39-44.
46. Mousavinasab SN, Yazdani Cherati J, Karami H, et al. Risk Factors Influencing the Survival of Pediatric Acute Leukemia Using Competing Risk Model. J Mazandaran Univ Med Sci. 2015;24(121):31-8.
47. Krauter J, Wagner K, Stadler M, et al. Prognostic factors in allo-SCT of elderly patients with AML. Bone Marrow Transplant. 2011;46(4):545-51.
48. Lipof JJ, Loh KP, O'Dwyer K, et al. Allogeneic Hematopoietic Cell Transplantation for Older Adults with Acute Myeloid Leukemia. Cancers 2018;10.
49. Hecker J, Miller I, Gotze KS, Verbeek M. Bridging Strategies to Allogeneic Transplant for Older AML Patients. Cancers (Basel) . 2018;10(6):179
50. Shokouhi S, Bray S, Bakhtiyari S, et al. Effects of aGVHD and cGVHD on Survival Rate in Patients with Acute Myeloid Leukemia after Allogeneic Stem Cell Transplantation. Int J Hematol Oncol Stem Cell Res. 2015;9(3):112-21.
51. Oran B, Weisdorf DJ. Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica. 2012;97(12):1916-24.
52. Almeida AM, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1-7.
53. Schmid C, Labopin M, Nagler A, et al. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. Blood. 2012;119(6):1599-606.
54. Sayemiri K, Eshraghian M, Mohammad K, et al. Predictive Factors of Survival Time after Hematopoietic Stem Cell Transplant in Acute Myeloid Leukemia Patients who Received Allogeneic BMT from Matched Sibling Donors Using Generalized Gamma Models. Int J Hematol Oncol Stem Cell Res. 2009;3(1):21-26.
|Issue||Vol 16, No 1 (2022)|
|Acute myeloid leukemia; Allogeneic stem cell transplantation; Survival analysis; Prognostic factors|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|