Abstract
Refined graft-versus-host disease (GVHD)/relapse-free survival (GRFS) considers main outcomes of allogeneic stem cell transplant (HSCT), estimating long-term survival without significant morbidity as a surrogate of HSCT success. We compared GRFS in 5059 adults with acute myeloid leukemia (AML), undergoing HSCT in first complete remission from 2000 to 2015 either from a matched sibling (MSD, n = 3731) or unrelated donor (MUD, n = 1328). Median age was 49 (range: 18–76) years. Median follow-up was 32 and 60 months in MSD and MUD, respectively (p < 0.01). Compared to MSD, at 4 years, MUD recipients had lower GRFS, with higher NRM, grade III–IV acute GVHD, and extensive chronic GVHD (HR: 1.42, p < 0.01). We also performed a risk factor analyses, showing unfavorable cytogenetics (HR: 1.42, p < 0.01) and peripheral blood as stem cell source (HR: 1.22, p < 0.01) associated to lower GRFS, while this was higher with in vivo T-cell depletion (TCD, HR: 0.73, p < 0.01) and shorter time from diagnosis to HSCT (HR 0.96, p < 0.01). Different factors, modifiable or not, such as donor type, stem cell source, disease biology, and in vivo TCD, impact on GRFS and this may guide in the future transplant choices to improve morbidity and long-term quality of life.
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References
Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood. 2000;96:4075–83.
Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. Registry. N Engl J Med. 2014;371:339–48.
Hambach L, Spierings E, Goulmy E. Risk assessment in haematopoietic stem cell transplantation: minor histocompatibility antigens. Best Pract Res Clin Haematol. 2007;20:171–87.
Remberger M, Mattsson J, Hentschke P, Aschan J, Barkholt L, Svennilson J, et al. The graft-versus-leukaemia effect in haematopoietic stem cell transplantation using unrelated donors. Bone Marrow Transpl. 2002;30:761–8.
Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn JY, et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002;100:406–14.
Weisdorf D, Zhang MJ, Arora M, Horowitz MM, Rizzo JD, Eapen M. Graft-versus-host disease induced graft-versus-leukemia effect: greater impact on relapse and disease-free survival after reduced intensity conditioning. Biol Blood Marrow Transplant. 2012;18:1727–33.
Kurosawa S, Yamaguchi T, Mori T, Kanamori H, Onishi Y, Emi N, et al. Patient-reported quality of life after allogeneic hematopoietic cell transplantation or chemotherapy for acute leukemia. Bone Marrow Transplant. 2015;50:1241–9.
Khera N, Storer B, Flowers ME, Carpenter PA, Inamoto Y, Sandmaier BM, et al. Nonmalignant late effects and compromised functional status in survivors of hematopoietic cell transplantation. J Clin Oncol. 2012;30:71–7.
Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333–8.
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.
Aoudjhane M, Labopin M, Gorin NC, Shimoni A, Ruutu T, Kolb HJ, et al. Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Leukemia. 2005;19:2304–12.
Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367:1487–96.
Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al. Refinement of cytogenetic classification in acute myeloid leukaemia: determination of prognostic significance of rarer recurring chromosomal abnormalities amongst 5876 younger adult patients treated in the UK Medical Research Council trials. Blood. 2010;116:354–65.
Cheson BD, 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;21:4642–9.
Shulman HM, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, 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.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
Fine JP, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.
Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014;124:344–53.
Saber W, Opie S, Rizzo JD, Zhang MJ, Horowitz MM, Schriber J. Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Blood. 2012;119:3908–16.
Ruggeri A, Battipaglia G, Labopin M, Ehninger G, Beelen D, Tischer J, et al. Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study. J Hematol Oncol. 2016;9:89.
Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ, 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;301:2349–61.
Solh M, Zhang X, Connor K, Brown S, Solomon SR, Morris LE, et al. Factors predicting graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation: multivariable analysis from a single center. Biol Blood Marrow Transplant. 2016;22:1403–9.
Yoon JH, Kim HJ, Park SS, Jeon YW, Lee SE, Cho BS, et al. Long-term clinical outcomes of hematopoietic cell transplantation for intermediate-to-poor-risk acute myeloid leukemia during first remission according to available donor types. Oncotarget. 2017;8:41590–604.
Nagler A, Labopin M, Shimoni A, Niederwieser D, Mufti GJ, Zander AR, et al. Mobilized peripheral blood stem cells compared with bone marrow as the stem cell source for unrelated donor allogeneic transplantation with reduced-intensity conditioning in patients with acute myeloid leukemia in complete remission: an analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012;18:1422–9.
Savani BN, Labopin M, Blaise D, Niederwieser D, Ciceri F, Ganser A, et al. Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT. Haematologica. 2016;101:256–62.
Inamoto Y, Kimura F, Kanda J, Sugita J, Ikegame K, Nakasone H, et al. Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups. Haematologica. 2016;101:1592–602.
Shaw BE, Gooley TA, Malkki M, Madrigal JA, Begovich AB, Horowitz MM, et al. The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation. Blood. 2007;110:4560–7.
Rubio MT, D’Aveni-Piney M, Labopin M, Hamladji RM, Sanz MA, Blaise D, et al. Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party. J Hematol Oncol. 2017;10:31.
Kroger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M, et al. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. N Engl J Med. 2016;374:43–53.
Acknowledgements
We thank Emmanuelle Polge from the office of the ALWP of EBMT.
Author contributions
GB, AR, AN designed the study. ML performed the statistical analysis. GB wrote the manuscript. AR, MM, and AN revised the manuscript and all the authors reviewed its final version. LV, DB, GS, RT, JJC, AG, AH, DW, IY-A, JM, PC were the principal investigators of the highest recruiting Centers of the study.
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Battipaglia, G., Ruggeri, A., Labopin, M. et al. Refined graft-versus-host disease/relapse-free survival in transplant from HLA-identical related or unrelated donors in acute myeloid leukemia. Bone Marrow Transplant 53, 1295–1303 (2018). https://doi.org/10.1038/s41409-018-0169-6
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DOI: https://doi.org/10.1038/s41409-018-0169-6
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