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Blood. 2016 Mar 17;127(11):1502-8. doi: 10.1182/blood-2015-10-672071. Epub 2016 Jan 13.

Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation.

Author information

1
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine.
2
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
3
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Biostatistics.
4
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and School of Pharmacy, and.
5
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Pediatrics, University of Washington, Seattle, WA.

Abstract

The cumulative incidence of National Institutes of Health (NIH)-defined chronic graft-versus-host disease (GVHD) requiring systemic treatment is ∼35% at 1 year after transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized blood cells from HLA-matched related or unrelated donors. We hypothesized that high-dose cyclophosphamide given after G-CSF-mobilized blood cell transplantation would reduce the cumulative 1-year incidence of chronic GVHD to 15% or less. Forty-three patients with high-risk hematologic malignancies (median age, 43 years) were enrolled between December 2011 and September 2013. Twelve (28%) received grafts from related donors, and 31 (72%) received grafts from unrelated donors. Pretransplant conditioning consisted of fludarabine and targeted busulfan (n = 25) or total body irradiation (≥12 Gy; n = 18). Cyclophosphamide was given at 50 mg/kg per day on days 3 and 4 after transplantation, followed by cyclosporine starting on day 5. The cumulative 1-year incidence of NIH-defined chronic GVHD was 16% (95% confidence interval, 5-28%). The cumulative incidence estimates of grades 2-4 and 3-4 acute GVHD were 77% and 0%, respectively. At 2 years, the cumulative incidence estimates of nonrelapse mortality and recurrent malignancy were 14% and 17%, respectively, and overall survival was projected at 70%. Of the 42 patients followed for ≥1 year, 21 (50%) were relapse-free and alive without systemic immunosuppression at 1 year after transplantation. Thus, myeloablative pretransplant conditioning can be safely combined with high-dose cyclophosphamide after transplantation, and the risk of chronic GVHD associated with HLA-matched mobilized blood cell grafts can be substantially reduced. This trial was registered at www.clinicaltrials.gov as #NCT01427881.

PMID:
26764356
PMCID:
PMC4797026
DOI:
10.1182/blood-2015-10-672071
[Indexed for MEDLINE]
Free PMC Article

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