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Single umbilical cord blood with or without CD34+ cells from a third-party donor in adults with leukemia.

ABSTRACT: We retrospectively compared the clinical outcomes of adults with acute leukemia who received single-unit umbilical cord blood (UCB) transplantation (sUCBT) (n = 135) or stem cell transplant using coinfusion of a UCB graft with CD34+ cells from a third-party donor (Haplo-Cord) (n = 72) at different institutions within the Grupo Español de Trasplante Hematopoyético. In multivariable analysis, patients in the Haplo-Cord group showed more rapid neutrophil (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.5-3.3; P < .001) and platelet recovery (HR, 1.6; 95% CI, 1.2-2.3; P = .015) and lower incidence of chronic graft-versus-host disease (GVHD) (relative risk, 0.5; 95% CI, 0.3-0.8; P = .01). Nonrelapse mortality, relapse, disease-free survival (DFS), and GVHD/relapse-free survival were similar in the 2 groups. Regarding disease-specific outcomes, DFS in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia patients was not significantly different; however, a significantly higher relapse rate was found in patients with AML treated with Haplo-Cord (HR, 2.3; 95% CI, 1-5.4; P = .04). Our study confirms that Haplo-Cord was an effective strategy to accelerate neutrophil and platelet recovery and shows that, in the context of specific treatment platforms, sUCBT and Haplo-Cord offer similar long-term outcomes.

SUBMITTER: Sanz J

PROVIDER: S-EPMC5728323 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Single umbilical cord blood with or without CD34<sup>+</sup> cells from a third-party donor in adults with leukemia.

Sanz Jaime J Kwon Mi M Bautista Guiomar G Sanz Miguel A MA Balsalobre Pascual P Piñana José Luis JL Solano Carlos C Duarte Rafael R Ferrá Christelle C Lorenzo Ignacio I Martín Carmen C Barba Pere P Pascual María Jesús MJ Martino Rodrigo R Gayoso Jorge J Buño Ismael I Regidor Carmen C de la Iglesia Almudena A Montoro Juan J Díez-Martín José Luis JL Sanz Guillermo F GF Cabrera Rafael R

Blood advances 20170620 15

We retrospectively compared the clinical outcomes of adults with acute leukemia who received single-unit umbilical cord blood (UCB) transplantation (sUCBT) (n = 135) or stem cell transplant using coinfusion of a UCB graft with CD34<sup>+</sup> cells from a third-party donor (Haplo-Cord) (n = 72) at different institutions within the Grupo Español de Trasplante Hematopoyético. In multivariable analysis, patients in the Haplo-Cord group showed more rapid neutrophil (hazard ratio [HR], 2.3; 95% conf ...[more]

PMID: 29296747

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Project description:BackgroundUmbilical cord blood (UCB) is a clinically relevant alternative source of hematopoietic stem/progenitor cells (HSPC). To overcome the low cell number per UCB unit, ex vivo expansion of UCB HSPC in co-culture with mesenchymal stromal cells (MSC) has been established. Bone marrow (BM)-derived MSC have been the standard choice, but the use of MSC from alternative sources, less invasive and discardable, could ease clinical translation of an expanded CD34+ cell product. Here, we compare the capacity of BM-, umbilical cord matrix (UCM)-, and adipose tissue (AT)-derived MSC, expanded with/without xenogeneic components, to expand/maintain UCB CD34+-enriched cells ex vivo.MethodsUCB CD34+-enriched cells were isolated from cryopreserved mononuclear cells and cultured for 7 days over an established feeder layer (FL) of BM-, UCM-, or AT-derived MSC, previously expanded using fetal bovine serum (FBS) or fibrinogen-depleted human platelet lysate (HPL) supplemented medium. UCB cells were cultured in serum-free medium supplemented with SCF/TPO/FLT3-L/bFGF. Fold increase in total nucleated cells (TNC) as well as immunophenotype and clonogenic potential (cobblestone area-forming cells and colony-forming unit assays) of the expanded hematopoietic cells were assessed.ResultsMSC from all sources effectively supported UCB HSPC expansion/maintenance ex vivo, with expansion factors (in TNC) superior to 50x, 70x, and 80x in UCM-, BM-, and AT-derived MSC co-cultures, respectively. Specifically, AT-derived MSC co-culture resulted in expanded cells with similar phenotypic profile compared to BM-derived MSC, but resulting in higher total cell numbers. Importantly, a subpopulation of more primitive cells (CD34+CD90+) was maintained in all co-cultures. In addition, the presence of a MSC FL was essential to maintain and expand a subpopulation of progenitor T cells (CD34+CD7+). The use of HPL to expand MSC prior to co-culture establishment did not influence the expansion potential of UCB cells.ConclusionsAT represents a promising alternative to BM as a source of MSC for co-culture protocols to expand/maintain HSPC ex vivo. On the other hand, UCM-derived MSC demonstrated inferior hematopoietic supportive capacity compared to MSC from adult tissues. Despite HPL being considered an alternative to FBS for clinical-scale manufacturing of MSC, further studies are needed to determine its impact on the hematopoietic supportive capacity of these cells.

Dataset Information

Single umbilical cord blood with or without CD34+ cells from a third-party donor in adults with leukemia.

Publications

Single umbilical cord blood with or without CD34<sup>+</sup> cells from a third-party donor in adults with leukemia.

Similar Datasets

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