BACKGROUND: Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated. METHODS: We analyzed 1554 adults with AML transplanted from MSD (n = 961) or UD (n = 593, HLA-matched 10/10, n = 481; 9/10, n = 112). Compared to MSD, UD recipients were older (49 vs 52 years, p = 0.001), transplanted more recently (2009 vs 2006, p = 0.001), and with a longer interval to transplant (10 vs 9 months, p = 0.001). Conditioning regimen was more frequently myeloablative for patients transplanted with a MSD (61 vs 46 %, p = 0.001). Median follow-up was 28 (range 3-157) months. RESULTS: Cumulative incidence (CI) of neutrophil engraftment (p = 0.07), grades II-IV acute GVHD (p = 0.11), chronic GVHD (p = 0.9), and non-relapse mortality (NRM, p = 0.24) was not different according to the type of donor. At 2 years, CI of relapse (relapse incidence (RI)) was 57 vs 49 % (p = 0.001). Leukemia-free survival (LFS) at 2 years was 21 vs 26 % (p = 0.001), and overall survival (OS) was 26 vs 33 % (p = 0.004) for MSD vs UD, respectively. Chronic GVHD as time-dependent variable was associated with lower RI (HR 0.78, p = 0.05), higher NRM (HR 1.71, p = 0.001), and higher OS (HR 0.69, p = 0.001). According to HLA match, RI was 57 vs 50 vs 45 %, (p = 0.001) NRM was 23 vs 23 vs 29 % (p = 0.26), and LFS at 2 years was 21 vs 27 vs 25 % (p = 0.003) for MSD, 10/10, and 9/10 UD, respectively. In multivariate analysis adjusted for differences between the two groups, UD was associated with lower RI (HR 0.76, p = 0.001) and higher LFS (HR 0.83, p = 0.001) compared to MSD. Interval between diagnosis and transplant was the other factor associated with better outcomes (RI (HR 0.62, p < 0.001) and LFS (HR 0.67, p < 0.001)). CONCLUSIONS: Transplantation using UD was associated with better LFS and lower RI compared to MSD for high-risk patients with AML transplanted in first relapse.

ALWP Office Hôpital Saint Antoine AP HP Paris France

Charité Universitatsmedizin 10117 Berlin Germany

Department of Bone Marrow Transplantation University Hospital Essen Essen Germany

Department of Haematology Oncology Helios Klinikum Berlin Buch Schwanebecker Chaussee 50 13125 Berlin Germany

Department of Hematology and Marrow Transplantation University Federico 2 of Naples Naples Italy

Department of Hematology Hemostasis Oncology and Stem Cell Transplantation Hannover Medical School Hannover Germany

Department of Hematology Lyon Sud Hospital Hospices Civils de Lyon Pierre Bénite France

Department of Hematology Oncology and Stem Cell Transplantation Asklepios Hospital St Georg Hamburg Germany

Department of Hematology Oncology and Stem Cell Transplantation University Medical Center Freiburg Germany

Department of Internal Medicine 3 UH of Munich Munich Germany

Department of Medicine A University of Muenster Munster Germany

Departments of Hematology Oncology Charles University Hospital Pilsen Czech Republic

Hematology Division Chaim Sheba Medical Center Tel Hashomer Israel

Hôpital Saint Antoine Paris University UPMC INSERM U938 Paris France

Medical Clinic and Polyclinic University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany

Service d'Hématologie et Thérapie Cellulaire Hôpital Saint Antoine AP HP 184 Rue du Faubourg Saint Antoine 75012 Paris France

Université Pierre and Marie Curie Paris France

University Medical Center Hamburg Eppendorf Hamburg Germany

Zobrazit více v PubMed

Burnett AK. Acute myeloid leukemia: treatment of adults under 60 years. Rev Clin Exp Hematol. 2002;6:26–45. doi: 10.1046/j.1468-0734.2002.00058.x. PubMed DOI

Nagler A, Savani B, Labopin M, et al. Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis. Lancet Haematol. 2015;2:e384–92. doi: 10.1016/S2352-3026(15)00146-5. PubMed DOI

McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001;97:3390–3400. doi: 10.1182/blood.V97.11.3390. PubMed DOI

Gragert L, Eapen M, Williams E, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371:339–48. doi: 10.1056/NEJMsa1311707. PubMed DOI PMC

Yakoub-agha I, Mesnil F, Kuentz M, et al. Allogeneic marrow stem-cell transplantation from human leukocyte antigen—identical siblings versus human leukocyte antigen–allelic–matched unrelated donors (10 / 10) in patients with standard-risk hematologic malignancy: a prospective study from the French Society of Bone Marrow Transplantation and Cell Therapy. J Clin Oncol. 2006;24:5695–5702. doi: 10.1200/JCO.2006.08.0952. PubMed DOI

Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukaemia: Determination of prognostic significance of rarer recurring chromosomal abnormalities amongst 5,876 younger adult patients treated in the UK Medical Research Council trials. Blood. 2010;116:354–365. doi: 10.1182/blood-2009-11-254441. PubMed DOI

Shulman H, Sullivan KM, Weiden PL, 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. doi: 10.1016/0002-9343(80)90380-0. PubMed DOI

Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–481. doi: 10.1080/01621459.1958.10501452. DOI

Fine JP, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509. doi: 10.1080/01621459.1999.10474144. DOI

Schmid C, Schleuning M, Ledderose G, et al. Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol. 2005;23:5675–5687. doi: 10.1200/JCO.2005.07.061. PubMed DOI

Duval M, Klein JP, He W, et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010;28:3730–3738. doi: 10.1200/JCO.2010.28.8852. PubMed DOI PMC

Schlenk RF, Dohner K, Mack S, et al. Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from matched related and matched unrelated donors in younger adults with high-risk acute myeloid leukemia: German-Austrian Trial AMLHD98A. J Clin Oncol. 2010;28:4642–4648. doi: 10.1200/JCO.2010.28.6856. PubMed DOI

Michallet M, Thomas X, Vernant JP, et al. Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Societé Française de Greffe de Moelle. Bone Marrow Transplant. 2000;26:1157–1163. doi: 10.1038/sj.bmt.1702690. PubMed DOI

Wong R, Shahjahan M, Wang X, et al. Prognostic factors for outcomes of patients with refractory or relapsed acute myelogenous leukemia or myelodysplastic syndromes undergoing allogeneic progenitor cell transplantation. Biol Blood Marrow Transplant. 2005;11:108–114. doi: 10.1016/j.bbmt.2004.10.008. PubMed DOI

Sayer HG, Kröger M, Beyer J, et al. Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor. Bone Marrow Transplant. 2003;31:1089–95. doi: 10.1038/sj.bmt.1704062. PubMed DOI

van Besien K, Artz A, Smith S, et al. Fludarabine, melphalan, and alemtuzumab conditioning in adults with standard-risk advanced acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol. 2005;23:5728–5738. doi: 10.1200/JCO.2005.15.602. PubMed DOI

Aoudjhane M, Labopin M, Gorin NC, 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;19:2304–2312. doi: 10.1038/sj.leu.2403967. PubMed DOI

Alyea EP, Kim HT, Ho V, et al. Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood. 2005;105:1810–1814. doi: 10.1182/blood-2004-05-1947. PubMed DOI

Shaw BE, Gooley TA, Malkki M, et al. The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation. Blood. 2007;110:4560–4567. doi: 10.1182/blood-2007-06-095265. PubMed DOI

Remberger M, Mattsson J, Hentschke P, et al. The graft-versus-leukaemia effect in haematopoietic stem cell transplantation using unrelated donors. Bone Marrow Transpl. 2002;30:761–768. doi: 10.1038/sj.bmt.1703735. PubMed DOI

Ringden O, Labopin M, Gluckman E, et al. Strong antileukemic effect of chronic graft-versus-host disease. Transplant Proc. 1997;29:733–734. doi: 10.1016/S0041-1345(96)00443-5. PubMed DOI

Lee SJ, Klein JP, Barrett AJ, et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002;100:406–414. doi: 10.1182/blood.V100.2.406. PubMed DOI

Weisdorf D, Zhang MJ, Arora M, et al. 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;18:1727–1733. doi: 10.1016/j.bbmt.2012.06.014. PubMed DOI PMC

Chevallier P, Labopin M, Socié G, et al. Results from a clofarabine-busulfan-containing, reduced-toxicity conditioning regimen prior to allogeneic stem cell transplantation: the phase 2 prospective CLORIC trial. Haematologica. 2014;99:1486–1491. doi: 10.3324/haematol.2014.108563. PubMed DOI PMC

Measurable residual disease status and outcome of transplant in acute myeloid leukemia in second complete remission: a study by the acute leukemia working party of the EBMT