Sirolimus associated pneumonitis after nonmyeloablative peripheral blood stem cell transplant for sickle cell disease.

Sirolimus is an immunosuppressant commonly used in solid organ transplantation as an alternative to corticosteroids or calcineurin inhibitors. Common side effects include hyperlipidemia, arthralgias, and noncardiac peripheral edema. Pulmonary toxicity is increasingly recognized after solid organ transplants [1-3]. Here we report the first case of sirolimus-associated pneumonitis (SAP) in a peripheral blood stem cell transplant (PBSCT) patient. A 21-year-old Puerto Rican woman with homozygous sickle cell disease (SCD) had a history of stroke as a child and frequent vaso-occlusive crises while on hydroxyurea. She met inclusion criteria and enrolled in an institutional review board-approved nonmyeloablative peripheral blood stem cell transplant study at the Clinical Center of the National Institutes of Health. She tolerated a low-dose radiation-based conditioning regimen and received a T-replete graft with 10 10 per kilogram CD34 cells from her HLA-matched sister. She experienced no sickle-related complications, and achieved prompt hematopoietic recovery. She was maintained on sirolimus only, targeting a trough level of 15-20 ng/mL. One year later, she was free of SCD: hemoglobin was 12 g/dL, hemoglobin electrophoresis was stable and compatible with her sickle trait donor, and 100% of peripheral blood CD14/15 leukocytes were of donor origin. She was regularly phlebotomized to correct transfusional iron overload. Sixteen months after the transplant, she developed cough, dyspnea on exertion, and progressed to debilitating dyspnea over a 4-week interval, but never required supplemental oxygen. There were no antecedent infections, CMV reactivation, acute or chronic GVHD (aGVHD, cGVHD), or other transplant-related complications. Upon admission to evaluate her dyspnea, she was afebrile with normal vital signs; her resting pulse oximetry was 99% to 100% on room air, which decreased to 95% after ambulating 100 meters. Her echocardiogram showed a normal ejection