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High-dose cyclophosphamide reduces incidence of GVHD following stem cell transplant
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The administration of cyclophosphamide following a mobilized blood cell transplant appeared associated with a lower incidence of chronic graft-versus-host disease, according to findings from a study conducted at Fred Hutchinson Cancer Research Center.
Graft-versus-host disease (GVHD) occurs when newly transplanted donor cells attack the organs of the recipient because they are identified as foreign. It is a complication that affects up to 80% of individuals who receive donor stem cell transplants.
Marco Mielcarek
Marco Mielcarek, MD , medical director of the adult blood and marrow transplant program for the Seattle Cancer Alliance and associate professor of medicine in the department of medical oncology at University of Washington, and colleagues conducted this study to determine whether the low incidence of chronic GVHD that is associated with the use of high-dose cyclophosphamide after a bone marrow transplant could be replicated in patients who received mobilized blood cell grafts.
Most institutions prefer to use mobilized cell grafts because those cells are easier to harvest and engraft faster, Mielcarek said in a press release. Mobilized blood stem cells are used in approximately 80% of transplants, and about 35% of these patients develop GVHD.
The primary endpoint of the study was the cumulative incidence of chronic GVHD requiring immunosuppressive treatment compared with the historic rate of 35%. Secondary endpoints included grade II to IV acute GVHD, the need for systemic treatment of GVHD, persistent or recurrent malignancy following hematopoietic cell transplant, DFS and OS.
The investigators enrolled 43 patients (median age, 43 years; range, 3-66 years) with high-risk hematologic malignancies onto the study between December 2011 and September 2013. This included patients with acute myeloid leukemia (40%), acute lymphoblastic leukemia (30%), myelodysplastic syndrome (21%), chronic myeloid leukemia (7%) and non-Hodgkin’s lymphoma (2%).
Patients received 50 mg/kg daily cyclophosphamide on days 3 and 4 following transplant. They also received cyclosporine starting on day 5, and tapering began on day 56 through day 126 in the absence of acute GVHD.
Median follow-up for surviving patients was 23 months (range, 6-38 months).
Twelve patients (28%) received grafts from related donors. The remaining received grafts from unrelated donors.
The cumulative incidence of chronic GVHD that required systemic immunosuppression at 1 year was 16% (95% CI, 5-28).
The estimated acute incidence of grade II to grade IV GVHD was 77%, and estimate acute incidence of grade III to grade IV GVHD was 0%.
At 2 years, the cumulative incidence of recurrent malignancy was 17% (95% CI, 5-29) and the cumulative incidence of nonrelapse mortality was 14% (95% CI, 4-25).
Estimated OS at 2 years was 70% (95% CI, 55-85) and the estimated PFS at 2 years was 69% (95% CI, 54-83).
Of the 42 patients followed for at least 1 year, 50% were relapse-free and alive without systemic immunosuppression 1 year following hematopoietic cell transplantation.
“Our finding that post-transplant cyclophosphamide reduced the relative risk of chronic GVHD in this setting by at least 50% is ... of great relevance for our transplant patients,” Mielcarek said in a press release. “If these findings are confirmed in future studies, mobilized blood cell transplantation may gain even greater acceptance and further replace marrow as a source of stem cells for most transplants.” – by Anthony SanFilippo
Disclosure: The researchers report no relevant financial disclosures.
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