Post-transplant Cyclophosphamide and Sirolimus Following Reduced Intensity Conditioning (RIC) Transplant

A Phase II Trial of Post-Transplant Cyclophosphamide and Sirolimus for Graft-versus-host Disease (GVHD) Prophylaxis Following Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation

This trial will evaluate the safety and efficacy of post-transplant Cy and sirolimus following reduced intensity allogeneic SCT. It is hoped that the combination of a reduced intensity preparative regimen with a calcineurin-free GVHD prophylaxis regimen will decrease the risk of acute and chronic GVHD, by both limiting mucosal toxicity and augmenting immune reconstitution, thereby improving the safety of the procedure. The past experience with post-transplant Cy suggests that SCT recipients will attain rapid donor T cell chimerism, which the investigators hope will translate into improved disease control through the well documented graft-versus-malignancy effects of donor T cells.

Inclusion Criteria:

• Availability of a 7/8 or 8/8 (HLA-A, B, C, DR) related or unrelated donor
• Age 18-75
• One of the following high-risk malignancies
• Chronic Myelogenous Leukemia
• Acute Myelogenous Leukemia
• Myelodysplastic Syndrome
• Myelofibrosis
• Acute Lymphocytic Leukemia
• Acute Lymphoblastic Lymphoma
• Chronic Lymphocytic Leukemia
• Prolymphocytic Leukemia
• Low-grade non-Hodgkin's Lymphoma
• Mantle Cell Lymphoma
• Hodgkin Lymphoma
• Myeloma

Exclusion Criteria:

• Poor cardiac function (EF <40%)
• Poor pulmonary function (FEV1 and FVC <50% predicted)
• Poor liver function (bilirubin >/= 2 mg/dl not due to hemolysis, Gilbert's or primary malignancy)
• Poor renal function (creatinine >/= 2 mg/dl or creatinine clearance <40mL/min)
• Karnofsky status <70%
• HIV positive