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Single-Agent Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis after Human Leukocyte Antigen-Matched Related Bone Marrow Transplantation for Pediatric and Young Adult Patients with Hematologic Malignancies.

ABSTRACT: High-dose cyclophosphamide given after HLA-matched related and unrelated allogeneic bone marrow transplantation (BMT) for patients with hematologic malignancies is effective single-agent graft-versus-host disease (GVHD) prophylaxis in adults. Data describing outcomes for pediatric and young adult patients have not been reported. Between the years 2007 and 2013, 29 pediatric and young adult patients ages ?21 years of age treated at our institution for high-risk hematologic malignancies underwent myeloablative HLA-matched related T cell-replete BMT. Eleven patients received post-transplantation cyclophosphamide (PTCy) as single-agent GVHD prophylaxis and were followed prospectively. Eighteen patients received calcineurin inhibitor (CNI)-based standard GVHD prophylaxis and were studied retrospectively as a control group. No acute GVHD (aGVHD) developed in patients receiving PTCy, whereas patients receiving CNI-based GVHD prophylaxis had cumulative incidences of grades II to IV and grades III and IV aGVHD of 27% and 5%, respectively. No patients receiving PTCy developed chronic GHVD, compared to 1 in the control group. Two-year overall survival was similar between the 2 groups (54% PTCy versus 58% CNI-based prophylaxis), as was event-free survival (42% PTCy versus 47% CNI-based). The 5-year cumulative incidence of relapse was 58% for PTCy and 42% for CNI-based GVHD prophylaxis (P = .45). These results suggest that PTCy is a safe and efficacious method of GVHD prophylaxis after an HLA-matched related BMT in the pediatric and young adult population that affords patients to be off all post-transplantation immunosuppression on day +5.

SUBMITTER: Jacoby E

PROVIDER: S-EPMC4706497 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Single-Agent Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis after Human Leukocyte Antigen-Matched Related Bone Marrow Transplantation for Pediatric and Young Adult Patients with Hematologic Malignancies.

Jacoby Elad E Chen Allen A Loeb David M DM Gamper Christopher J CJ Zambidis Elias E Llosa Nicolas J NJ Huo Jeffrey J Cooke Kenneth R KR Jones Rick R Fuchs Ephraim E Luznik Leo L Symons Heather J HJ

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20150904 1

High-dose cyclophosphamide given after HLA-matched related and unrelated allogeneic bone marrow transplantation (BMT) for patients with hematologic malignancies is effective single-agent graft-versus-host disease (GVHD) prophylaxis in adults. Data describing outcomes for pediatric and young adult patients have not been reported. Between the years 2007 and 2013, 29 pediatric and young adult patients ages ≤21 years of age treated at our institution for high-risk hematologic malignancies underwent ...[more]

PMID: 26343947

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Project description:Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality. We explored whether seven of these plasma-derived proteins, as measured by enzyme-linked immunosorbent assays, were predictive of clinical outcomes in post-transplantation cyclophosphamide-treated patients using plasma samples collected at serial predetermined timepoints from patients treated on prospective clinical studies of human leukocyte antigen-haploidentical (n=58; clinicaltrials.gov Identifier: 00796562) or human leukocyte antigen-matched-related or -unrelated (n=100; clinicaltrials.gov Identifiers: 00134017 and 00809276) T-cell-replete bone marrow transplantation. Day 30 levels of interleukin-2 receptor ?, tumor necrosis factor receptor 1, serum STimulation-2 (IL1RL1 gene product), and regenerating islet-derived 3-? all had high areas under the curve of 0.74-0.97 for predicting non-relapse mortality occurrence by 3 months post-transplant in both the human leukocyte antigen-matched and human leukocyte antigen-haploidentical cohorts. In both cohorts, all four of these proteins were also predictive of subsequent non-relapse mortality occurring by 6, 9, or 12 months post-transplant and were significantly associated with non-relapse mortality in univariable analyses. Furthermore, day 30 elevations of interleukin-2 receptor ? were associated with grade II-IV and III-IV acute graft-versus-host disease occurring after day 30 in both cohorts. These data confirm that plasma-derived proteins previously assessed in other transplantation platforms appear to retain prognostic and predictive utility in patients treated with post-transplantation cyclophosphamide.

Dataset Information

Single-Agent Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis after Human Leukocyte Antigen-Matched Related Bone Marrow Transplantation for Pediatric and Young Adult Patients with Hematologic Malignancies.

Publications

Single-Agent Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis after Human Leukocyte Antigen-Matched Related Bone Marrow Transplantation for Pediatric and Young Adult Patients with Hematologic Malignancies.

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