Infants with leukemia who require hematopoietic cell transplantation (HCT) remain 1 of the most significant challenges in pediatric stem cell transplant. Infant leukemia is characterized by a unique biology including a predominance mixed lineage leukemia(MLL) gene rearrangement and juvenile myelomonocytic leukemia. Moreover, the long-term effects of transplantation are particularly prominent in infants who have active endocrine, cardiovascular, pulmonary, neurologic, musculoskeletal, hearing, and vision development, with the added risk of second malignant neoplasms. Currently, there is no solid basis to support allogeneic HCT as first-line therapy for infant acute lymphoblastic leukemia-first remission (ALL-CR1), although indicated for other infant leukemias, including juvenile myelomonocytic leukemia (JMML). The relative long-term toxicity of total body irridiation (TBI) versus non-TBI containing preparative regimens for HCT in infants remains controversial, with the differences, especially on neurocognitive function, unknown.