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Published in: Journal of Hematology & Oncology 1/2016

Open Access 01-12-2016 | Research

Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study

Authors: Annalisa Ruggeri, Giorgia Battipaglia, Myriam Labopin, Gerhard Ehninger, Dietrich Beelen, Johanna Tischer, Arnold Ganser, Rainer Schwerdtfeger, Bertram Glass, Jurgen Finke, Mauricette Michallet, Matthias Stelljes, Pavel Jindra, Renate Arnold, Nicolaus Kröger, Mohamad Mohty, Arnon Nagler

Published in: Journal of Hematology & Oncology | Issue 1/2016

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Abstract

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.
Literature
1.
go back to reference Burnett AK. Acute myeloid leukemia: treatment of adults under 60 years. Rev Clin Exp Hematol. 2002;6:26–45.CrossRefPubMed Burnett AK. Acute myeloid leukemia: treatment of adults under 60 years. Rev Clin Exp Hematol. 2002;6:26–45.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
3.
go back to reference 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;97:3390–400.CrossRefPubMed 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;97:3390–400.CrossRefPubMed
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference 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;24:5695–702.CrossRefPubMed 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;24:5695–702.CrossRefPubMed
6.
go back to reference 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;116:354–65.CrossRefPubMed 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;116:354–65.CrossRefPubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
go back to reference Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.CrossRef Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.CrossRef
9.
go back to reference Fine JP, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.CrossRef Fine JP, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.CrossRef
10.
go back to reference 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;23:5675–87.CrossRefPubMed 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;23:5675–87.CrossRefPubMed
11.
go back to reference 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;28:3730–8.CrossRefPubMedPubMedCentral 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;28:3730–8.CrossRefPubMedPubMedCentral
12.
go back to reference 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;28:4642–8.CrossRefPubMed 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;28:4642–8.CrossRefPubMed
13.
go back to reference 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;26:1157–63.CrossRefPubMed 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;26:1157–63.CrossRefPubMed
14.
go back to reference 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;11:108–14.CrossRefPubMed 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;11:108–14.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference 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;23:5728–38.CrossRefPubMed 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;23:5728–38.CrossRefPubMed
17.
go back to reference 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;19:2304–12.CrossRefPubMed 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;19:2304–12.CrossRefPubMed
18.
go back to reference 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;105:1810–4.CrossRefPubMed 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;105:1810–4.CrossRefPubMed
19.
go back to reference Shaw BE, Gooley TA, Malkki M, et al. The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation. Blood. 2007;110:4560–7.CrossRefPubMed Shaw BE, Gooley TA, Malkki M, et al. The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation. Blood. 2007;110:4560–7.CrossRefPubMed
20.
go back to reference 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;30:761–8.CrossRef 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;30:761–8.CrossRef
21.
go back to reference Ringden O, Labopin M, Gluckman E, et al. Strong antileukemic effect of chronic graft-versus-host disease. Transplant Proc. 1997;29:733–4.CrossRefPubMed Ringden O, Labopin M, Gluckman E, et al. Strong antileukemic effect of chronic graft-versus-host disease. Transplant Proc. 1997;29:733–4.CrossRefPubMed
22.
go back to reference Lee SJ, Klein JP, Barrett AJ, et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002;100:406–14.CrossRefPubMed Lee SJ, Klein JP, Barrett AJ, et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002;100:406–14.CrossRefPubMed
23.
go back to reference 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;18:1727–33.CrossRefPubMedPubMedCentral 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;18:1727–33.CrossRefPubMedPubMedCentral
24.
go back to reference 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;99:1486–91.CrossRefPubMedPubMedCentral 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;99:1486–91.CrossRefPubMedPubMedCentral
Metadata
Title
Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study
Authors
Annalisa Ruggeri
Giorgia Battipaglia
Myriam Labopin
Gerhard Ehninger
Dietrich Beelen
Johanna Tischer
Arnold Ganser
Rainer Schwerdtfeger
Bertram Glass
Jurgen Finke
Mauricette Michallet
Matthias Stelljes
Pavel Jindra
Renate Arnold
Nicolaus Kröger
Mohamad Mohty
Arnon Nagler
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2016
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-016-0321-y

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