Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis

Abstract

Results of unrelated cord blood transplantation (UCBT) in childhood acute myeloid leukemia (AML) have not been previously reported. We analyzed 95 children receiving UCB transplants for AML (20 in first complete remission [CR1], 47 in CR2, and 28 in more advanced stage). Poor prognosis cytogenetic abnormalities were identified in 29 cases. Most patients received a 1 or 2 HLA antigens-mismatched UCB transplants. The median number of collected nucleated cells (NCs) was 5.2 ؋ 10 7 / kg. Cumulative incidence (CI) of neutrophil recovery was 78% ؎ 4%, acute graftversus-host disease (GVHD) was 35% ؎ 5%, and 100-day transplantation-related mortality (TRM) was 20% ؎ 4%. In multivariable analysis, a collected NC dose higher than 5.2 ؋ 10 7 /kg was associated with a lower 100-day TRM. The 2-year CI of relapse was 29% ؎ 5% and was associated with disease status. The 2-year leukemia-free survival (LFS) was 42% ؎ 5% (59% ؎ 11% in CR1, 50% ؎ 8% in CR2, and 21% ؎ 9% for children not in CR). Children with poor prognosis cytogenetic features had similar LFS compared with other patients (44% ؎ 11% vs 40% ؎ 8%). In CR2, LFS was not influenced by the length of CR1 (53% ؎ 11% in CR1 < 9.5 months compared with 50% ؎ 12% in later relapses). We conclude that UCBT is a therapeutic option for children with very poorprognosis AML and who lack an HLAidentical sibling. IntroductionBone marrow transplantation (BMT) from an HLA-matched sibling or unrelated donor plays a major role in the treatment of children with relapsed acute myeloid leukemia (AML). [1][2][3][4][5][6] However, although there are currently more than 8 million donors registered in marrow donor registries around the world, a substantial proportion of children who lack a sibling donor will never undergo BMT from an HLA-matched unrelated donor either because such a donor cannot be found or because the time to identify a donor is too long. Moreover, for those children who received unrelated bone marrow transplants, increased HLA disparity adversely affects survival because of high risk of graft-versus-host disease (GVHD) and opportunistic infections. [7][8][9] The use of haploidentical family donors provides a potential source of hematopoietic stem cells for children who lack both a sibling and an unrelated donor. [10][11] T-cell depletion of the graft can in part overcome the risk of severe GVHD, but it substantially increases the risk of severe and prolonged posttransplantation immunodeficiency.Hematopoietic stem cells from an unrelated cord blood (UCB) transplant can restore hematopoiesis and immune function after a myeloablative conditioning regimen, even if the graft is not perfectly HLA identical to the recipient. [12][13][14][15] This important medical advance led to the establishment of large cord blood banks that made possible the use of UCB to provide transplants for patients who lack a conventional related or unrelated donor. In addition, UCB offers the advantage of significantly faster availability of banked cryopreserved UCB units compared with the availability of u...

Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.

“…2,8 In the past few years, several studies have documented that transplantation of unrelated CB cells in children with CR1 AML is associated with a favorable outcome, particularly in patients aged less than 1 year at time of diagnosis. [9][10][11] The use of high-resolution molecular typing techniques for selecting an unrelated donor (UD) has also dramatically reduced the risk of immune-mediated complications and TRM, thus widening the indications for HSCT from an unrelated volunteer, which now are in part coincident with those for matched-related HSCT. 12,13 Although largely used in the past, 14,15 more recently the role of autologous (AUTO) HSCT has been questioned, especially in view of similar efficacy to repeated courses of intensive high-dose cytarabine (HD-AraC)-based consolidation chemotherapy for prevention of disease recurrence.…”

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

“…Minor histocompatibility antigen disparity is expectedly greater between unrelated individuals. Despite the use of HLA class I and II disparate grafts, the incidence and severity of acute GVHD observed in pediatric and adult recipients of UCB grafts is lower when compared to recipients of unrelated adult donor grafts [6,9,11,13,16,28].…”

Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation

“…[2][3][4][5][6][7] Compared with BMT, UCBT offers the clinical advantages of absence of risks for the donor, reduced risk of transmitting infections, reduced incidence and severity of GVHD and, for transplants from UDs, rapid availability of cryopreserved cells, with the median time for a successful donor search being o1 month. 2,3,[8][9][10][11][12] Results of UCBT from either an HLA-compatible sibling or from a UD have been reported to be comparable with those obtained in children transplanted with BM cells.…”