Reduced‐intensity allogeneic hematopoietic cell transplantation: Graft versus tumor effects with decreased toxicity

The potentially curative role of allogeneic hematopoietic cell transplantation (HCT) in neoplastic and non‐neoplastic diseases is offset by the substantial risks of morbidity and mortality from complications of the intensive myeloablative and immunosuppressive preparative regimen. These regimen‐related toxicities have restricted allogeneic HCT to young, otherwise healthy individuals without comorbid diseases. Pediatric patients undergoing conventional allogeneic HCT have lower procedure‐related mortality but are at risk for non‐fatal late effects of the high‐dose pretransplant chemoradiotherapy, such as growth retardation, sterility and other endocrine dysfunction. Evaluation of reduced‐intensity preparative regimens is the major focus of current clinical research in allogeneic HCT. Reduced‐intensity HCT (RI‐HCT) relies on the use of immunosuppressive but non‐myeloablative agents that allow engraftment of donor cells, which provide adoptive allogeneic cellular immunotherapy and graft versus tumor (GVT) effects, with decreased regimen‐related toxicities. Although the experience with RI‐HCT in pediatric patients is very limited at this time, results in adults indicate that attenuated‐dose preparative regimens allow older patients and those with organ dysfunction to undergo successful allogeneic HCT with acceptable morbidity and mortality. In adults, the potency of the allogeneic GVT effect varies among neoplastic diseases, with better results observed in patients with indolent hematological malignancies or renal cell carcinoma. The effectiveness of RI‐HCT as treatment for children with hemoglobinopathies, chronic granulomatous disease and cellular immunodeficiencies is encouraging, and the role of reduced‐intensity preparative regimens for allogeneic HCT in pediatric malignancies is under investigation.