Allogeneic hematopoietic cell transplantation: from experimental biology to clinical care

Purpose: For more than half a century, researchers have explored myeloablative, high-dose chemo/radiotherapy followed by allogeneic hematopoietic stem cell transplantation (HCT) for therapy of malignant and nonmalignant hematological diseases. Continuous advances in the field have changed this approach from one that was initially thought to be fraught by insurmountable complications to one that is now considered standard therapy for many diseases. Methods: In order to extend allogeneic HCT to include elderly patients, who represent the main population affected by hematological malignancies, and to those who are medically unfit to undergo conventional HCT, novel nonmyeloablative approaches have been developed. These approaches rely on graft-vs-tumor effects for tumor eradication rather than high-dose chemoradiotherapy, and, accordingly, have lower toxicities than conventional regimens. Results: Results with nonmyeloablative regimens have been gratifying, and this may change the future of allogeneic HCT. Advances could not have been possible without basic research and studies in pre-clinical animal models. Conclusion: Further work is focused on improving graft-vs-tumor effects while achieving better control of graft-vs-host disease.