Rasburicase to Prevent Graft -Versus-Host Disease
- To evaluate the incidence and severity of acute graft-vs-host disease (GVHD) in
rasburicase-treated patients who will undergo myeloablative HLA-matched related or
unrelated donor allogeneic peripheral blood hematopoietic stem cell transplantation
(SCT) for hematologic malignancies and compare these outcomes with those of historical
- To evaluate the efficacy (in terms of reduction of uric acid levels) and safety of
rasburicase in patients undergoing myeloablative allogeneic SCT.
- To evaluate the graft-versus-host and host-versus-graft immune responses in
OUTLINE: This is a multicenter study.
Patients receive a conventional myeloablative conditioning regimen consisting of high doses
of cyclophosphamide, busulfan, and etoposide, with or without total-body irradiation.
Depending on the preparative regimen selected, the conditioning of recipients will take a
total of 6 to 7 days. On day 0, patients will receive filgrastim (G-CSF)-mobilized
HLA-matched, related, or unrelated donor allogeneic peripheral blood stem cells
(unmanipulated). Patients will receive standard graft-vs-host disease prophylaxis consisting
of cyclosporine or tacrolimus and methotrexate or sirolimus. Patients will receive
rasburicase IV over 30 minutes, beginning on the first day of conditioning therapy, for 5
consecutive days. If after 5 days of rasburicase the patient's uric acid plasma level
remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.
Blood is obtained on day 0 and then at 14, 28, and 42 days post-transplant for immunologic
studies, including quantitative analysis to follow the recovery of T cells, B cells, natural
killer cells, dendritic cells (DC), and monocytes using flow cytometry (FCM); phenotypic
analysis of T cells, DC and monocytes by FCM; lymphocyte activation analysis: CD3, CD4, CD8,
CD25 2. CD3, CD8, CD71, CD69; DC analysis: CD45, CD14, DR, CD86, CD80 2. CD45, CD14, CD40,
CD11c; and in vitro functional studies such as mixed lymphocyte reaction (MLR) and
cell-mediated lysis (CML) to assess for the graft-versus-host and host-versus-graft
responses. Peripheral blood is collected for chimerism studies on days 28 and 100
After completion of study treatment, patients are followed periodically.
Masking: Open Label, Primary Purpose: Supportive Care
Incidence and severity of acute graft-vs-host disease
Bimalangshu R. Dey, MD, PhD
Massachusetts General Hospital
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|