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Remobilization of hematopoietic stem cells in healthy donors for allogeneic transplantation.

ABSTRACT: The need to repeat peripheral blood (PB) stem cell mobilization and collection in healthy donors arises infrequently but may be required due to insufficient initial collection, graft failure, or relapse of the recipient's disease. Little data exist on the efficacy of remobilization. Therefore, we retrospectively reviewed 18 years of remobilization records from healthy stem cell donors at our institution.We identified 62 healthy donors who underwent remobilization, a cohort of 30 mobilized and remobilized with cytokines and a cohort of 32 mobilized with a CXCR4 antagonist and remobilized with cytokines. For each cohort we compared the PB CD34+/L level, the number of CD34+ cells collected/kg (recipient weight), and the number of CD34+ cells/L collected on the first day of leukapheresis during initial mobilization and remobilization.Initial mobilization with cytokines was associated with reduced remobilization. The mean PB CD34/L level at initial mobilization was 69 × 10(6) compared to 37 × 10(6) at remobilization (p?=?0.029). In contrast, initial mobilization with a CXCR4 antagonist was not associated with reduced remobilization. The mean PB CD34/L level at initial mobilization was 15 × 10(6) compared to 68 × 10(6) at remobilization (p?

SUBMITTER: Fiala MA

PROVIDER: S-EPMC5205536 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Remobilization of hematopoietic stem cells in healthy donors for allogeneic transplantation.

Fiala Mark A MA Park Soo S Slade Michael M DiPersio John F JF Stockerl-Goldstein Keith E KE

Transfusion 20160617 9

<h4>Background</h4>The need to repeat peripheral blood (PB) stem cell mobilization and collection in healthy donors arises infrequently but may be required due to insufficient initial collection, graft failure, or relapse of the recipient's disease. Little data exist on the efficacy of remobilization. Therefore, we retrospectively reviewed 18 years of remobilization records from healthy stem cell donors at our institution.<h4>Study design and methods</h4>We identified 62 healthy donors who under ...[more]

PMID: 27311884

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Project description:BACKGROUND:Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative therapeutic approach for different hematological malignancies (HMs), and epigenetic modifications, including DNA methylation, play a role in the reconstitution of the hematopoietic system after AHSCT. This study aimed to explore global DNA methylation dynamic of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) from donors and their respective recipients affected by acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and Hodgkin lymphoma (HL) during the first year after transplant. METHODS:We measured DNA methylation profile by Illumina HumanMethylationEPIC in BM HSPC of 10 donors (t0) and their matched recipients at different time points after AHSCT, at day +?30 (t1), +?60 (t2), +?120 (t3), +?180 (t4), and +?365 (t5). Differential methylation analysis was performed by using R software and CRAN/Bioconductor packages. Gene set enrichment analysis was carried out on promoter area of significantly differentially methylated genes by clusterProfiler package and the mSigDB genes sets. RESULTS:Results show significant differences in the global methylation profile between HL and acute leukemias, and between patients with mixed and complete chimerism, with a strong methylation change, with prevailing hyper-methylation, occurring 30?days after AHSCT. Functional analysis of promoter methylation changes identified genes involved in hematopoietic cell activation, differentiation, shaping, and movement. This could be a consequence of donor cell "adaptation" in recipient BM niche. Interestingly, this epigenetic remodeling was reversible, since methylation returns similar to that of donor HSPCs after 1 year. Only for a pool of genes, mainly involved in dynamic shaping and trafficking, the DNA methylation changes acquired after 30?days were maintained for up to 1 year post-transplant. Finally, preliminary data suggest that the methylation profile could be used as predictor of relapse in ALL. CONCLUSIONS:Overall, these data provide insights into the DNA methylation changes of HSPCs after transplantation and a new framework to investigate epigenetics of AHSCT and its outcomes.

Project description:BACKGROUND: Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival. METHODS: The diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. RESULTS: Sixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes - gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) - and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03). CONCLUSIONS: One of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.

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Remobilization of hematopoietic stem cells in healthy donors for allogeneic transplantation.

Publications

Remobilization of hematopoietic stem cells in healthy donors for allogeneic transplantation.

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