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      Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

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          Abstract

          Allogeneic hematopoietic stem cell transplantation is the optimal care for patients with high-risk or intermediate - acute myeloid leukemia. In patients lacking matched sibling donor, haploidentical donors are an option. We compared outcomes of unmanipulated (Haplo) to matched sibling donor transplant in acute myeloid leukemia patients in first complete remission. Included were intermediate and high-risk acute myeloid leukemia in first complete remission undergoing Haplo and matched sibling donor transplant from 2007–2015, and reported to the ALWP of the EBMT. A propensity score technique was used to confirm results of main analysis: 2 matched sibling donors were matched with 1 Haplo. We identified 2654 pts (Haplo =185; matched sibling donor =2469), 2010 with intermediate acute myeloid leukemia (Haplo=122; matched sibling donor =1888) and 644 with high-risk acute myeloid leukemia (Haplo =63; matched sibling donor =581). Median follow up was 30 (range 1–116) months. In multivariate analysis, in intermediate - acute myeloid leukemia patients, Haplo resulted in lower leukemia-free survival (Hazard Ratio 1.74; P<0.01), overall-survival (HR 1.80; P<0.01) and GvHD-free-relapse-free survival (Hazard Ratio 1.32; P<0.05) and higher graft- versus-host disease (GvHD) non-relapse mortality (Hazard Ratio 3.03; P<0.01) as compared to matched sibling donor. In high-risk acute myeloid leukemia, no differences were found in leukemia-free survival, overall-survival, and GvHD-free- relapse-free survival according to donor type. Higher grade II-IV acute GvHD was observed for Haplo in both high-risk (Hazard Ratio 2.20; P<0.01) and intermediate risk (Hazard Ratio 1.84; P<0.01). A trend for a lower Relapse-Incidence was observed in Haplo among high-risk acute myeloid leukemia (Hazard Ratio 0.56; P=0.06). The propensity score analysis confirmed results. Our results underline that matched sibling donor is the first choice for acute myeloid leukemia patients in first complete remission. On the other hand, results of Haplo transplants are similar to matched sibling donor transplants in acute myeloid leukemia patients with high risk cytogenetics.

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          Most cited references34

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          MatchIt: Nonparametric Preprocessing for Parametric Causal Inference

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            HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry.

            Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord-blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry. Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose. Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor--that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit--that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background. Most patients likely to benefit from HSCT will have a donor. Public investment in donor recruitment and cord-blood banks has expanded access to HSCT. (Funded by the Office of Naval Research, Department of the Navy, and the Health Resources and Services Administration, Department of Health and Human Services.).
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              Chronic graft-versus-host disease.

              Chronic graft-versus-host disease (GVHD) remains a vexing and dangerous complication of allogeneic stem cell transplantation. Mild forms of chronic GVHD are often manageable with local or low-dose systemic immunosuppression and do not affect long-term survival. In contrast, more severe forms of chronic GVHD require intensive medical management and adversely affect survival. This report reviews current concepts of the pathogenesis, clinical risk factors, classification systems, organ manifestations, and available treatments for chronic GVHD. It also provides a comprehensive listing of the published clinical trials aimed at prevention and primary treatment of chronic GVHD. Copyright 2003 American Society for Blood and Marrow Transplantation
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                Author and article information

                Journal
                Haematologica
                Haematologica
                haematol
                Haematologica
                Haematologica
                Ferrata Storti Foundation
                0390-6078
                1592-8721
                August 2018
                10 May 2018
                : 103
                : 8
                : 1317-1328
                Affiliations
                [1 ]Service d’Hématologie et Thérapie Cellulaire Hôpital Saint Antoine, Paris, France
                [2 ]Hematology Department, Federico II University, Naples, Italy
                [3 ]Hospital Saint-Antoine, Paris University UPMC, France
                [4 ]Acute Leukemia Working Party of EBMT, Paris, France
                [5 ]Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children’s Hospital, Roma, Italy
                [6 ]Shariati Hospital, Hematology-Oncology and BMT Research, Teheran, Iran
                [7 ]Haematology and BMT Unit, IRCCS Ospedale San Raffaele, Milano, Italy
                [8 ]Programme de Transplantation &Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, France
                [9 ]Stem Cell Transplant Unit, Policlinico Universitario Tor Vergata, Rome, Italy
                [10 ]Hopital St. Louis, Dept.of Hematology – BMT, Paris, France
                [11 ]Hematology department, Institut Gustave Roussy, Villejuif, France
                [12 ]Ospedale San Martino, Department of Haematology II Genova
                [13 ]A.O.U. Città della Salute e della Scienza, Torino, Italy
                [14 ]Institut Universitaire du Cancer Toulouse, Oncopole, France
                [15 ]Unità Terapia Intensiva Ematologica per il Trapianto Emopoietico, Ospedale Civile, Pescara, Italia
                [16 ]Hopital Jean Minjoz, Service d’Hématologie, Besançon, France
                [17 ]Chaim Sheba Medical Center, Tel-Hashomer, Israel
                Author notes
                Article
                1031317
                10.3324/haematol.2018.189258
                6068036
                29748438
                d5349d2c-e066-427c-8223-bad0327fcc3e
                Copyright© 2018 Ferrata Storti Foundation

                Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions:

                https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions:

                https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.

                History
                : 22 January 2018
                : 10 May 2018
                Categories
                Article
                Acute Myeloid Leukemia

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