Hematopoietic stem cell transplantation for infants with high-risk KMT2A gene rearranged acute lymphoblastic leukemia.

The role of allogeneic hematopoietic stem cell transplantation (HSCT) for infants with acute lymphoblastic leukemia (ALL) and KMT2A gene rearrangement (KMT2A-r) is controversial in terms of both its efficacy and potential of acute and late toxicities. In the Japanese Pediatric Leukemia/Lymphoma Study Group trial MLL-10, by introducing intensive chemotherapy, indication of HSCT was restricted to the patients with high-risk (HR) features only (KMT2A-r and either age <180 days or presence of central nervous system leukemia). Of the 56 HR patients, 49 achieved complete remission. Forty-three patients received HSCT in first remission including the 38 patients receiving protocol-specified HSCT with conditioning consisting of individualized targeted doses of busulfan, etoposide, and cyclophosphamide. Three-year event-free survival (EFS) of 56.8% (95%CI, 42.4%-68.8%) and overall survival of 80.2% (95%CI, 67.1%-88.5%) were accomplished. Univariable analysis showed Interfant-HR criteria and flowcytometric minimal residual disease (MRD) ≥0.01% both at end of induction and at end of consolidation (EOC) were significantly associated with poorer EFS. In the multivariable analysis, positive MRD at EOC was solely associated with poor EFS (P<0.001). Rapid pre-transplant MRD clearance and tailored HSCT strategy in the MLL-10 trial resulted in a favorable outcome for infants with HR KMT2A-r ALL. However, considering the high rate of potentially life-threatening toxicities and risk of late effects, its indication should be further restricted or even eliminated in the future by introducing more effective therapeutic modalities with minimal toxicities. This trial was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.