Atorvastatin as GVHD Prophylaxis for Allogeneic Hematopoietic Cell Transplantation

Acute graft-versus-host disease (GVHD) is one of the most frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT).(1) It develops in 30-75% of recipients of allogeneic HSCT depending on the degree of histocompatibility between the donor and the recipient, number of T-cells in the graft, recipient's age and GVHD prophylactic regimen used. (2-4) Novel strategies designed to effectively prevent the development of this life threatening complication of allogeneic transplantation are urgently needed.

Inclusion criteria

• Patients with a history of a hematological malignancy or bone marrow failure syndrome suitable for allogeneic stem cell transplantation in the opinion of treating transplant physician.
• Patients aged 18-75 years of age are eligible. Patients with age > 18 and ≤ 50 years will be eligible for myeloablative conditioning (MAC), while patients > 50 years of age, or those with previous history of autologous transplantation, high hematopoietic cell transplant comorbidity index (HCT-CI) score (>2), and baseline diagnosis of hodgkin's lymphoma, chronic lymphocytic leukemia and follicular lymphoma will be suitable for reduced intensity conditioning (RIC) transplantation (however intensity of conditioning regimen will remain at the discretion of treating physician).
• All patients must have at least one suitable human leukocyte antigen (HLA)-matched sibling or unrelated donor according to transplant center's guidelines (for selection of appropriate sibling donor).
• Patient must provide informed consent.
• Left ventricular ejection fraction ≥ 40%.
• Bilirubin ≤ 2 x the upper limit of normal (ULN) and aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 3 x ULN; and absence of hepatic cirrhosis. For patients with Gilbert's syndrome, bilirubin ≤ 3 x ULN is permitted.
• Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation.
• Carbon monoxide diffusing capacity (DLCOcor) corrected for hemoglobin or forced expiratory volume at one second (FEV1) or DL/VA ≥ 40% of predicted (a pulmonary function test).
• Karnofsky performance status > 70.
• A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
• Patients with positive HIV serology are eligible.
• Patients who have previously been taking atorvastatin or any other statin drug will be eligible as long as there is no contraindication to switch to atorvastatin (40mg/day) in the opinion of the treating physician.
• Method of stem-cell collection from the sibling donor will be at the discretion of the treating physician. Although it is anticipated that majority of sibling donors will undergo Granulocyte colony-stimulating factor(G-CSF) induced stem cell mobilization; however donors undergoing bone marrow harvest or stem cell mobilization with experimental agents (e.g. plerixafor) will remain eligible for the study.

Exclusion criteria

• Uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart failure.
• Evidence of active bacterial, viral or fungal infection at the time of transplant conditioning.
• History of intolerance or allergic reactions with atorvastatin will not be eligible.
• Undergoing a T-cell depleted allogeneic transplantation
• Receiving conditioning regimens containing anti-thymocyte globulin, and/or campath