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Comparison of reduced intensity and nonmyeloablative conditioning for adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation in first or second remission

Bone Marrow Transplantation volume 58, pages 377–385 (2023)Cite this article

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Abstract

Reduced intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning regimens have expanded use of allogeneic hematopoietic cell transplantation (HCT) in AML to include older and medically less-fit patients, but relative efficacies and toxicities remain poorly defined. Here, we analyzed outcomes from 343 adults transplanted in remission after RIC (n = 137) or NMA (n = 206) conditioning between 2006 and 2021. The characteristics of RIC and NMA HCT patients were similar except that RIC patients were younger and their time between most recent remission achievement and allografting was shorter. There were no significant differences in relapse risk, relapse-free survival (RFS), overall survival (OS), and non-relapse mortality (NRM) between RIC and NMA HCT patients, both overall (relapse: hazard ratio [HR] = 0.80, P = 0.27; RFS: HR = 0.93, P = 0.61; OS: HR = 0.93, P = 0.66; NRM: HR = 1.13, P = 0.59) and when patients were stratified by pre-HCT measurable residual disease (MRD) status. After multivariable adjustment, there was no statistically significant association between conditioning intensity and relapse (HR = 0.69, P = 0.088), RFS (HR = 0.86, P = 0.37), OS (HR = 0.89, P = 0.49), or NRM (HR = 1.37, P = 0.19). In this non-randomized cohort of adults undergoing allografting for AML in first or second remission at our center, we could not detect statistically significant differences in outcomes between those assigned to RIC and those assigned to NMA conditioning.

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Fig. 1: Cumulative incidences of acute and chronic GVHD, stratified by conditioning intensity.
Fig. 2: Post-HCT outcomes for 343 adults with AML undergoing allogeneic HCT while in first or second morphologic remission after RIC or NMA conditioning, stratified by conditioning intensity.
Fig. 3: Post-HCT outcomes for 343 adults with AML undergoing allogeneic HCT while in first or second morphologic remission after RIC or NMA conditioning, stratified by conditioning intensity and pre-HCT MRD status.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Döhner H, Wei AH, Appelbaum FR, Craddock C, Di Nardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140:1345–77.

    Article  PubMed  Google Scholar 

  2. Pingali SR, Champlin RE. Pushing the envelope-nonmyeloablative and reduced intensity preparative regimens for allogeneic hematopoietic transplantation. Bone Marrow Transpl. 2015;50:1157–67.

    Article  CAS  Google Scholar 

  3. Jethava YS, Sica S, Savani B, Socola F, Jagasia M, Mohty M, et al. Conditioning regimens for allogeneic hematopoietic stem cell transplants in acute myeloid leukemia. Bone Marrow Transpl. 2017;52:1504–11.

    Article  CAS  Google Scholar 

  4. Lipof JJ, Loh KP, O’Dwyer K, Liesveld JL. Allogeneic hematopoietic cell transplantation for older adults with acute myeloid leukemia. Cancers 2018;10:179.

  5. Magliano G, Bacigalupo A. Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia of the elderly: review of literature and new perspectives. Mediterr J Hematol Infect Dis. 2020;12:e2020081.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Luger SM, Ringdén O, Zhang MJ, Pérez WS, Bishop MR, Bornhäuser M, et al. Similar outcomes using myeloablative vs reduced-intensity allogeneic transplant preparative regimens for AML or MDS. Bone Marrow Transpl. 2012;47:203–11.

    Article  CAS  Google Scholar 

  7. Martino R, de Wreede L, Fiocco M, van Biezen A, von dem Borne PA, Hamladji RM. et al. Comparison of conditioning regimens of various intensities for allogeneic hematopoietic SCT using HLA-identical sibling donors in AML and MDS with <10% BM blasts: a report from EBMT. Bone Marrow Transpl. 2013;48:761–70.

    Article  CAS  Google Scholar 

  8. Heinicke T, Labopin M, Polge E, Niederwieser D, Platzbecker U, Sengelov H, et al. Fludarabine/busulfan versus fludarabine/total-body-irradiation (2 Gy) as conditioning prior to allogeneic stem cell transplantation in patients (>/=60 years) with acute myelogenous leukemia: a study of the acute leukemia working party of the EBMT. Bone Marrow Transpl. 2020;55:729–39.

    Article  CAS  Google Scholar 

  9. Blaise D, Tabrizi R, Boher JM, Le Corroller-Soriano AG, Bay JO, Fegueux N, et al. Randomized study of 2 reduced-intensity conditioning strategies for human leukocyte antigen-matched, related allogeneic peripheral blood stem cell transplantation: prospective clinical and socioeconomic evaluation. Cancer. 2013;119:602–11.

    Article  CAS  PubMed  Google Scholar 

  10. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.

    Article  CAS  PubMed  Google Scholar 

  11. Morsink LM, Othus M, Bezerra ED, Wood BL, Fang M, Sandmaier BM, et al. Impact of pre-transplant measurable residual disease on outcome of allogeneic hematopoietic cell transplantation in adult monosomal karyotype AML. Leukemia. 2020;34:1577–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Morsink LM, Sandmaier BM, Othus M, Palmieri R, Granot N, Bezerra ED et al. Conditioning intensity, pre-transplant flow cytometric measurable residual disease, and outcome in adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. Cancers. 2020;12:2339.

  13. Paras G, Morsink LM, Othus M, Milano F, Sandmaier BM, Zarling LC, et al. Conditioning intensity and peritransplant flow cytometric MRD dynamics in adult AML. Blood. 2022;139:1694–706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zarling LC, Othus M, Sandmaier BM, Milano F, Schoch G, Davis C, et al. Utility of the Treatment-Related Mortality (TRM) score to predict outcomes of adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. Leukemia. 2022;36:1563–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Orvain C, Wilson JA, Fang M, Sandmaier BM, Rodríguez-Arbolí E, Wood BL et al. Relative impact of residual cytogenetic abnormalities and flow cytometric measurable residual disease on outcome after allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia. Haematologica. 2022. https://doi.org/10.3324/haematol.2022.281585 Online ahead of print.

  16. Rodríguez-Arbolí E, Orvain C, Othus M, Walter RB. Significance of measurable residual disease in adults with secondary acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2022;57:1732-4.

    Article  PubMed  Google Scholar 

  17. Rodríguez-Arbolí E, Othus M, Orvain C, Zarling LC, Sandmaier BM, Milano F, et al. Contribution of measurable residual disease status to prediction accuracy of relapse and survival in adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. Haematologica. 2022. https://doi.org/10.3324/haematol.2022.281631 Online ahead of print.

  18. Orvain C, Byelykh M, Othus M, Sandmaier BM, Schoch G, Davis C, et al. Relationship between pre-transplant nutritional status and outcomes of adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. Transplant Cell Ther. 2022;28:846.e1–9.

    Article  Google Scholar 

  19. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Walter RB, Othus M, Borthakur G, Ravandi F, Cortes JE, Pierce SA, et al. Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J Clin Oncol. 2011;29:4417–23.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Breems DA, Van Putten WLJ, De Greef GE, Van Zelderen-Bhola SL, Gerssen-Schoorl KBJ, Mellink CHM, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008;26:4791–7.

    Article  PubMed  Google Scholar 

  22. Leisenring WM, Martin PJ, Petersdorf EW, Regan AE, Aboulhosn N, Stern JM, et al. An acute graft-versus-host disease activity index to predict survival after hematopoietic cell transplantation with myeloablative conditioning regimens. Blood. 2006;108:749–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transpl. 2015;21:389–401 e381.

    Article  Google Scholar 

  24. Craddock C, Jackson A, Loke J, Siddique S, Hodgkinson A, Mason J, et al. Augmented reduced-intensity regimen does not improve postallogeneic transplant outcomes in acute myeloid leukemia. J Clin Oncol. 2021;39:768–78.

    Article  CAS  PubMed  Google Scholar 

  25. Walter RB, Gooley TA, Wood BL, Milano F, Fang M, Sorror ML, et al. Impact of pretransplantation minimal residual disease, as detected by multiparametric flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute myeloid leukemia. J Clin Oncol. 2011;29:1190–7.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Walter RB, Buckley SA, Pagel JM, Wood BL, Storer BE, Sandmaier BM, et al. Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission. Blood. 2013;122:1813–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Walter RB, Gyurkocza B, Storer BE, Godwin CD, Pagel JM, Buckley SA, et al. Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia. 2015;29:137–44.

    Article  CAS  PubMed  Google Scholar 

  28. Araki D, Wood BL, Othus M, Radich JP, Halpern AB, Zhou Y, et al. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: is it time to move toward a minimal residual disease-based definition of complete remission. J Clin Oncol. 2016;34:329–36.

    Article  PubMed  Google Scholar 

  29. Zhou Y, Othus M, Araki D, Wood BL, Radich JP, Halpern AB, et al. Pre- and post-transplant quantification of measurable (‘minimal’) residual disease via multiparameter flow cytometry in adult acute myeloid leukemia. Leukemia. 2016;30:1456–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wood BL. Acute myeloid leukemia minimal residual disease detection: the difference from normal approach. Curr Protoc Cytom. 2020;93:e73.

    CAS  PubMed  Google Scholar 

  31. Walter RB, Sandmaier BM, Storer BE, Godwin CD, Buckley SA, Pagel JM, et al. Number of courses of induction therapy independently predicts outcome after allogeneic transplantation for acute myeloid leukemia in first morphological remission. Biol Blood Marrow Transpl. 2015;21:373–8.

    Article  Google Scholar 

  32. Hoffmann AP, Besch AL, Othus M, Morsink LM, Wood BL, Mielcarek M, et al. Early achievement of measurable residual disease (MRD)-negative complete remission as predictor of outcome after myeloablative allogeneic hematopoietic cell transplantation in acute myeloid leukemia. Bone Marrow Transpl. 2020;55:669–72.

    Article  Google Scholar 

  33. Morsink LM, Bezerra ED, Othus M, Wood BL, Fang M, Sandmaier BM, et al. Comparative analysis of total body irradiation (TBI)-based and non-TBI-based myeloablative conditioning for acute myeloid leukemia in remission with or without measurable residual disease. Leukemia. 2020;34:1701–5.

    Article  PubMed  Google Scholar 

  34. Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010;28:2859–67.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Krakow EF, Gyurkocza B, Storer BE, Chauncey TR, McCune JS, Radich JP, et al. Phase I/II multisite trial of optimally dosed clofarabine and low-dose TBI for hematopoietic cell transplantation in acute myeloid leukemia. Am J Hematol. 2020;95:48–56.

    Article  CAS  PubMed  Google Scholar 

  36. Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, et al. Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2017;35:1154–61.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Scott BL, Pasquini MC, Fei M, Fraser R, Wu J, Devine SM, et al. Myeloablative versus reduced-Intensity conditioning for hematopoietic cell transplantation in acute myelogenous leukemia and myelodysplastic syndromes-long-term follow-up of the BMT CTN 0901 clinical trial. Transpl Cell Ther. 2021;27:483 e481–483 e486.

    Article  Google Scholar 

  38. Hourigan CS, Dillon LW, Gui G, Logan BR, Fei M, Ghannam J, et al. Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease. J Clin Oncol. 2020;38:1273–83.

    Article  CAS  PubMed  Google Scholar 

  39. Buckley SA, Wood BL, Othus M, Hourigan CS, Ustun C, Linden MA, et al. Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis. Haematologica. 2017;102:865–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hourigan CS, Gale RP, Gormley NJ, Ossenkoppele GJ, Walter RB. Measurable residual disease testing in acute myeloid leukaemia. Leukemia. 2017;31:1482–90.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Research reported in this publication was supported by grants P01-CA078902, P01-CA018029, and P30-CA015704 from the National Cancer Institute/National Institutes of Health (NCI/NIH), Bethesda, MD, USA. The authors acknowledge the excellent care provided by the physicians advanced practice providers, dietitians, pharmacists, and nurses of the HCT teams, the staff in the Long-Term Follow-up office at the Fred Hutchinson Cancer Center, the Hematopathology Laboratory at the University of Washington, and the patients for participating in our research protocols.

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Authors and Affiliations

  1. Fred Hutchinson Cancer Center, Seattle, WA, USA

    Roland B. Walter, Brenda M. Sandmaier, Megan Othus, Corentin Orvain, Eduardo Rodríguez-Arbolí, Masumi U. Oshima, Gary Schoch, Chris Davis, H. Joachim Deeg & Rainer Storb

  2. Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA

    Roland B. Walter & Corentin Orvain

  3. Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA

    Roland B. Walter

  4. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Roland B. Walter

  5. Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA

    Brenda M. Sandmaier, Masumi U. Oshima, H. Joachim Deeg & Rainer Storb

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Contributions

RBW, BMS, and RS conceptualized and designed this study and participated in data analysis and interpretation and drafting of the manuscript. BMS, MUO, HJD, and RS contributed to the provision of study material, patient recruitment, and acquisition of data. MO conducted all statistical analyses and participated in data interpretation. CO, ERA, GS, and CD contributed to the collection and assembly of data. All authors revised the manuscript critically and gave final approval to submit for publication.

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Correspondence to Roland B. Walter.

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Walter, R.B., Sandmaier, B.M., Othus, M. et al. Comparison of reduced intensity and nonmyeloablative conditioning for adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation in first or second remission. Bone Marrow Transplant 58, 377–385 (2023). https://doi.org/10.1038/s41409-022-01909-x

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