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Trends in outcome of transplantation in patients with secondary acute myeloid leukemia: an analysis from the Acute Leukemia Working Party (ALWP) of the EBMT

Bone Marrow Transplantation volume 57, pages 1788–1796 (2022)Cite this article

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A Correction to this article was published on 24 October 2022

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Abstract

Trends in outcome of transplantation (HSCT) in secondary acute myeloid leukemia (sAML) are limited. We evaluated results of HSCT in 4224 patients with sAML in complete remission; 1337 were transplanted in 2000–2010 and 2887 in 2011–2020. Median age was 54 (range, 18–74) and 59 (range, 18–78) years, respectively (p < 0.0001). Donors were MSD in 65% vs. 37%, 10/10 UD in 27% vs. 50%, and 9/10 UD in 8% vs. 13%, respectively (p < 0.0001). Conditioning was myeloablative in 46% and 38%, respectively. Two-year non-relapse mortality (NRM) was lower in patients transplanted in 2011–2020 vs. those transplanted in 2000–2010, 18% vs. 21% (hazard ratio (HR) = 0.82, 95% CI: 0.68–0.9; p = 0.04) and modified GVHD-free, relapse-free survival (GRFS) (HR = 0.9, 95% CI: 0.81–0.99; p = 0.04) was better in patients transplanted in the 2011–2020 vs. those transplanted in 2000–2010. Two-year relapse incidence (RI) was similar between the 2 groups with 32% vs. 31%, (HR = 1.05, 95% CI: 0.9–1.22; p = 0.55). Likewise, leukemia-free survival (LFS) (HR = 0.95, 95% CI: 0.84–1.07; p = 0.38) and overall survival (OS) (HR = 0.93, 95% CI: 0.82–1.05; p = 0.26) were not significantly different between the two periods. In conclusion, Incidence of NRM has been significantly reduced and GRFS significantly increased in HSCT for sAML in the last 2 decades.

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Fig. 1: Results of unrelated transplantation in patients with secondary acute myeloid leukemia (sAML) comparing outcomes of two cohorts according to the year of transplant (2000–2010 and 2011–2019).

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AN, MN, ML, and MM had full access to all the data in the study (available upon data specific request).

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References

  1. Granfeldt Ostgard LS, Medeiros BC, Sengelov H, Norgaard M, Andersen MK, Dufva IH, et al. Epidemiology and clinical significance of secondary and therapy-related acute MSecondary AML is generally associated with poor clinical outcomes compared to de novo AMLyeloid Leukemia: a National Population-Based Cohort Study. J Clin Oncol. 2015;33:3641–9.

    Article  PubMed  Google Scholar 

  2. Hulegårdh E, Nilsson C, Lazarevic V, Garelius H, Antunovic P, Rangert Derolf Å, et al. Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish Acute Leukemia Registry. Am J Hematol. 2015;90:208–14.

    Article  PubMed  Google Scholar 

  3. Della Porta MG. Prognosis of secondary acute myeloid leukemia. Leuk Res. 2013;37:857–8.

    Article  PubMed  Google Scholar 

  4. Park SH, Chi H-S, Cho Y-U, Jang S, Park C-J. Evaluation of prognostic factors in patients with therapy-related acute myeloid leukemia. Blood Res. 2013;48:185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol. 2001;19:1405–13.

    Article  CAS  PubMed  Google Scholar 

  6. Kayser S, Döhner K, Krauter J, Köhne C-H, Horst HA, Held G, et al. German-Austrian AMLSG. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood. 2011;117:2137–45.

    Article  CAS  PubMed  Google Scholar 

  7. Zeichner SB, Arellano ML. Secondary adult acute myeloid leukemia: a review of our evolving understanding of a complex disease process. Curr Treat Options Oncol. 2015;16:37.

    Article  PubMed  Google Scholar 

  8. Litzow MR, Tarima S, Perez WS, Bolwell BJ, Cairo MS, Camitta BM, et al. Allogeneic transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia. Blood. 2010;115:1850–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sengsayadeth S, Labopin M, Boumendil A, Finke J, Ganser A, Stelljes M, et al. Transplant outcomes for secondary acute myeloid leukemia: acute leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study. Biol Blood Marrow Transplant. 2018;24:1406–14.

    Article  PubMed  Google Scholar 

  10. Schmaelter A-K, Labopin M, Socié G, Itälä-Remes M, Blaise D, Yakoub-Agha I, et al. Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia. Blood Cancer J. 2020;10:26.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kida M, Usuki K, Uchida N, Fukuda T, Katayama Y, Kondo T, et al. Outcome and risk factors for therapy-related myeloid neoplasms treated with allogeneic stem cell transplantation in Japan. Biol Blood Marrow Transplant. 2020; 26:1543–51.

  12. Nilsson C, Hulegårdh E, Garelius H, Möllgård L, Brune M, Wahlin A, et al. Secondary acute myeloid leukemia and the role of allogeneic stem cell transplantation in a population-based setting. Biol Blood Marrow Transplant. 2019;25:1770–8.

    Article  PubMed  Google Scholar 

  13. Appelbaum FR. Improved outcomes with allogeneic hematopoietic cell transplantation. Best Pract Res Clin Haematol. 2012;25:465–71.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Penack O, Peczynski C, Mohty M, Yakoub-Agha I, Styczynski J, Montoto S, et al. How much has allogeneic stem cell transplant-related mortality improved since the 1980s? A retrospective analysis from the EBMT. Blood Adv. 2020;4:6283–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Canaani J, Beohou E, Labopin M, Ghavamzadeh A, Beelen D, Hamladji RM, et al. Trends in patient outcome over the past two decades following allogeneic stem cell transplantation for acute myeloid leukaemia: an ALWP/EBMT analysis. J Intern Med. 2019;285:407–41.

    Article  CAS  PubMed  Google Scholar 

  16. McDonald GB, Sandmaier BM, Mielcarek M, Sorror M, Pergam SA, Cheng GS, et al. Survival, nonrelapse mortality, and relapse-related mortality after allogeneic hematopoietic cell transplantation: comparing 2003-7 versus 2013-7 Cohort. Ann Intern Med. 2020;172:229–39.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Shouval R, Fein JA, Labopin M, Cho C, Bazarbachi A, Baron F, et al. Development and validation of a disease risk stratification system for patients with haematological malignancies: a retrospective cohort study of the European Society for Blood and Marrow Transplantation registry. Lancet Haematol. 2021;8:e205–15.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Vasudevan Nampoothiri R, Law AD, Lam W, Chen C, Al-Shaibani Z, Loach D, et al. Predictors of outcomes of therapy-related acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Hematol Oncol Stem Cell Ther. 2021;S1658-3876(21)00032-7. https://doi.org/10.1016/j.hemonc.2021.03.003.

  19. Kröger N, Brand R, van Biezen A, Zander A, Dierlamm J, Niederwieser D, et al. Myelodysplastic Syndromes Subcommittee of The Chronic Leukaemia Working Party of European Group for Blood and Marrow Transplantation (EBMT) Risk factors for therapy-related myelodysplastic syndrome and acute myeloid leukemiatreated with allogeneic stem cell transplantation. Haematologica. 2009;94:542–9.

  20. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:825–8.

    CAS  PubMed  Google Scholar 

  22. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.

    Article  CAS  PubMed  Google Scholar 

  23. Ruggeri A, Labopin M, Ciceri F, Mohty M, Nagler A. Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP-EBMT analysis on patients with AML in remission. Bone Marrow Transplant. 2016;51:610–1.

    Article  CAS  PubMed  Google Scholar 

  24. Kanate AS, Nagler A, Savani B. Summary of scientific and statistical methods, study endpoints and definitions for observational and registry-based studies in hematopoietic cell transplantation. Clin Hematol Int. 2019;2:2–4.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Andersen PK, Klein JP, Zhang MJ. Testing for center effects in multi-center survival studies: a Monte Carlo comparison of fixed and random effects tests. Stat Med. 1999;18:1489–500.

    Article  CAS  PubMed  Google Scholar 

  26. R Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing. 2017. https://www.R-project.org/.

  27. A language and environment for statistical computing. https://www.R-project.org/. R Core Team: R Foundation for Statistical Computing, Vienna, Austria.; 2020.

  28. Schetelig J, de Wreede LC, van Gelder M, Koster L, Finke J, Niederwieser D, et al. Late treatment-related mortality versus competing causes of death after allogeneic transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia. Leukemia. 2019;33:686–95.

  29. Yakoub-Agha I, de La Salmonie’re P, Ribaud P, Sutton L, Wattel E, Kuentz M, et al. Allogeneic bone marrow transplantation fortherapy-related myelodysplastic syndrome and acute myeloidleukemia: a long-term study of 70 patients-report of the French society of bone marrow transplantation. J Clin Oncol. 2000;18:963–71.

    Article  CAS  PubMed  Google Scholar 

  30. Tsirigotis P, Byrne M, Schmid C, Baron F, Ciceri F, Esteve J, et al. Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT. Bone Marrow Transplant. 2016;51:1431–8.

    Article  CAS  PubMed  Google Scholar 

  31. Schmid C, De Wreede LC, Van Biezen A, Finke J, Ehninger G, Ganser A, et al. Outcome after relapse of myelodysplastic syndrome and secondary acute myeloid leukemia following allogeneic stem cell transplantation: a retrospective registry analysis on 698 patients by the Chronic Malignancies Working Party of the European Society of B. Haematologica. 2018;103:237–45.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Bazarbachi A, Schmid C, Labopin M, Beelen D, Wolfgang Blau I, Potter V, et al. Evaluation of trends and prognosis over time in patients with AML relapsing after allogeneic hematopoietic cell transplant reveals improved survival for young patients in recent years. Clin Cancer Res. 2020;26:6475–82.

    Article  CAS  PubMed  Google Scholar 

  33. Craddock C, Labopin M, Robin M, Finke J, Chevallier P, Yakoub-Agha I, et al. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica. 2016;101:879–83.

  34. Bazarbachi A, Labopin M, Battipaglia G, Djabali A, Passweg J, Socié G, et al. Sorafenib improves survival of FLT3-mutated acute myeloid leukemia in relapse after allogeneic stem cell transplantation: a report of the EBMT Acute Leukemia Working Party. Haematologica. 2019;104:e398.

  35. Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, Jabbour E, et al. Acute myeloid leukemia: current progress and future directions. Blood Cancer J. 2021;11:41.

  36. Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, et al. Cortes JE.CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8:e481–91.

    Article  PubMed  Google Scholar 

  37. Oliai C, Schiller G. How to address second and therapy-related acute myelogenous leukaemia. Br J Haematol. 2020;188:116–28.

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Acknowledgements

We thank all of the European Society for Blood and Marrow Transplantation (EBMT) centers and national registries for contributing patients to this study (Supplementary Appendix Material). We also thank the data managers for their excellent work and the patients who have contributed data.

Author information

Authors and Affiliations

  1. Division of Hematology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel

    Arnon Nagler

  2. EBMT Paris study office, Department of Haematology, Saint Antoine Hospital, INSERM UMR 938, Sorbonne University, Paris, France

    Maud Ngoya, Jacques-Emmanuel Galimard, Myriam Labopin & Mohamad Mohty

  3. Department of Haematology, Saint Antoine Hospital, INSERM UMR 938, Sorbonne University, Paris, France

    Myriam Labopin & Mohamad Mohty

  4. Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

  5. Inserm U976, APHP, Hopital St. Louis, Dept. of Hematology—BMT, University of Paris, Paris, France

    Gerard Socié

  6. Rikshospitalet Clinic for Cancer Medicine, Hematology Dept. Section for Stem Cell Transplantation, Oslo University Hospital, Oslo, Norway

    Tobias Gedde-Dahl

  7. Kings College Hospital, Dept. of Haematological Medicine, King’s Denmark Hill Campus, London, UK

    Victoria Potter

  8. Dept. of Bone Marrow Transplantation, University Hospital, Essen, Germany

    Thomas Schroeder

  9. Medical Clinic and Policinic 1, Hematology and Cellular Therapy, University hospital, Leipzig, Germany

    Uwe Platzbecker

  10. Department of Haematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    Arnold Ganser

  11. Programme de Transplantation & Therapie Cellulaire Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France

    Didier Blaise

  12. Comprehensive Cancer Center, Stem Cell Transplantation Unit, HUCH, Helsinki, Finland

    Urpu Salmenniemi

  13. Dept. of Hematology, University Hospital Gasthuisberg, Leuven, Belgium

    Johan Maertens

  14. Queen Elizabeth Medical Centre, Edgbaston, Dept. of Haematology, University Hospital Birmingham NHS Trust, Birmingham, UK

    Charles Craddock

  15. Centre Hospitalier Lyon Sud, Service Hematologie, Lyon, France

    Hélène Labussière-Wallet

  16. CHU de Lille, INSERM, Univ Lille, Lille, France

    Ibrahim Yakoub-Agha

  17. Vanderbilt University Medical Center, Nashville, TN, USA

    Bipin Savani

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Contributions

AN wrote the paper, designed the study, and interpreted the data. MN, ML, and MM designed the study, performed the statistical analyses, interpreted the data, and edited the paper. NK, GS, TGD, VP, TS, UP, AG, DB, US, TM, CC, HLW, IYA, and BS reviewed the paper and provided clinical data. All authors approved the final version of the paper.

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Correspondence to Arnon Nagler.

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The authors declare no competing interests.

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The scientific boards of the ALWP of the EBMT approved this study.

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The original online version of this article was revised: In the original version of this article, the given and family names of Jacques-Emmanuel Galimard were incorrectly structured.

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Nagler, A., Ngoya, M., Galimard, JE. et al. Trends in outcome of transplantation in patients with secondary acute myeloid leukemia: an analysis from the Acute Leukemia Working Party (ALWP) of the EBMT. Bone Marrow Transplant 57, 1788–1796 (2022). https://doi.org/10.1038/s41409-022-01825-0

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