Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia from a Matched Donor versus an HLA-Identical Sibling: Is the Outcome Comparable? Results from the International BFM ALL SCT 2007 Study
Adriana Balduzzi, Jean-Hugues Dalle, Jacek Wachowiak, Isaac Yaniv, Akif Yesilipek, Petr Sedlacek, Marc Bierings, Marianne Ifversen, Sabina Sufliarska, Krzysztof Kalwak, Arjan Lankester, Jacek Toporski, Lucia Di Maio, Evgenia Glogova, Ulrike Poetschger, Christina Peters, Adriana Balduzzi, Jean-Hugues Dalle, Jacek Wachowiak, Isaac Yaniv, Akif Yesilipek, Petr Sedlacek, Marc Bierings, Marianne Ifversen, Sabina Sufliarska, Krzysztof Kalwak, Arjan Lankester, Jacek Toporski, Lucia Di Maio, Evgenia Glogova, Ulrike Poetschger, Christina Peters
Abstract
Eligibility criteria for hematopoietic stem cell transplantation (HSCT) in acute lymphoblastic leukemia (ALL) vary according to disease characteristics, response to treatment, and type of available donor. As the risk profile of the patient worsens, a wider degree of HLA mismatching is considered acceptable. A total of 138 children and adolescents who underwent HSCT from HLA-identical sibling donors (MSDs) and 210 who underwent HSCT from matched donors (MDs) (median age, 9 years; 68% male) in 10 countries were enrolled in the International-BFM ALL SCT 2007 prospective study to assess the impact of donor type in HSCT for pediatric ALL. The 4-year event-free survival (65 ± 5% vs 61 ± 4%; P = .287), overall survival (72 ± 4% versus 68 ± 4%; P = .235), cumulative incidence of relapse (24 ± 4% versus 25 ± 3%; P = .658) and nonrelapse mortality (10 ± 3% versus 14 ± 3%; P = .212) were not significantly different between MSD and MD graft recipients. The risk of extensive chronic (cGVHD) was lower in MD graft recipients than in MSD graft recipients (hazard ratio [HR], .38; P = .002), and the risks of severe acute GVHD (aGVHD) and cGVHD were higher in peripheral blood stem cell graft recipients than in bone marrow graft recipients (HR, 2.06; P = .026). Compared with the absence of aGVHD, grade I-II aGVHD was associated with a lower risk of graft failure (HR, .63; P = .042) and grade III-IV aGVHD was associated with a higher risk of graft failure (HR, 1.85; P = .020) and nonleukemic death (HR, 8.76; P < .0001), despite a lower risk of relapse (HR, .32; P = .021). Compared with the absence of cGVHD, extensive cGVHD was associated with a higher risk of nonleukemic death (HR, 8.12; P < .0001). Because the outcomes of transplantation from a matched donor were not inferior to those of transplantation from an HLA-identical sibling, eligibility criteria for transplantation might be reviewed in pediatric ALL and possibly in other malignancies as well. Bone marrow should be the preferred stem cell source, and the addition of MTX should be considered in MSD graft recipients.
Trial registration: ClinicalTrials.gov NCT01423500.
Keywords: Acute lymphoblastic leukemia; Chronic graft-versus-host disease; Hematopoietic stem cell transplantation; Pediatric; Transplantation-related mortality.
Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Source: PubMed