Major breakthroughs in hematopoietic stem cell transplantation and future challenges in clinical implementation

The Haitian proverb “Beyond mountains, there are mountains” has many meanings. One that resonates for hematopoietic stem cell transplantation (HCT) over the last 50-plus years is the sense that as you solve one problem, another presents itself. To mark the 100th anniversary of the JCI, we focus on the evolving understanding of major HCT hurdles, those surmounted, challenges that lie ahead (Figure 1), and how these have been chronicled through key JCI papers. Hematopoietic stem cell transplantation Hematopoietic stem cell transplantation (HCT) is a curative therapy for many malignant and nonmalignant hematologic diseases, including treatment-refractory leukemia, classical hematologic diseases (e.g., sickle cell disease), congenital and acquired immune system disorders (e.g., severe combined immune deficiency), and inborn errors of metabolism (e.g., Hurler syndrome). Allogeneic HCT refers to a transplant where donor BM, peripheral blood–based stem cell, or umbilical cord blood products are infused into a patient after myeloablative or nonmyeloablative conditioning regimens involving irradiation and/or chemotherapy; these are designed to make room for donor stem cells, immune suppress the host to permit donor graft acceptance, and eliminate residual malignant cells. Autologous HCT refers to infusion of the patient’s own stem cells to restore hematopoiesis. Despite considerable successes, multiple challenges still loom.