Late Effects in Survivors of Infant Acute Lymphoblastic Leukemia from the 3 Consecutive Japanese Nationwide Clinical Trials

Background Very few studies have reported the incidence of and risk factor for late effects of infant leukemia. In addition, the long-term impact of a preparative regimen for very young children undergoing allogeneic stem cell transplantation (SCT) is not evident. Method To examine the late effects in survivors of infant acute lymphoblastic leukemia (ALL) treated on the Japanese Infant Leukemia Study Group (JILSG) trials MLL96, MLL98 and the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) trial MLL03, we performed a cross-sectional survey using questionnaires by the attending pediatricians from 2015 to 2017. In all 3 studies, infants with KMT2A gene rearranged (MLL-R) ALL were allocated to receive SCT in their first remission. Choice of preparative regimen was left to the physician's choice in the MLL96/98 studies, while use of non-total body irradiation (TBI) regimen with busulfan (BU) was mandatory in the MLL03 study. Results Seventy out of 102 (69%) eligible subjects were evaluated: 33 were males and 37 were females. 62 patients had an MLL-R ALL. The median age of diagnosis was 5.5 months (range, 0-12m) and 35 (50%) were Conclusion In this study, survivors of infant leukemia had prolonged and various types of late effects. We observed serious growth failure in height and weight in patients treated with SCT and it was further pronounced in the TBI group and in the multiple SCT (BU+TBI) group. More than half of the patients had dental late effects and a third of all the patients had thyroid dysfunctions, which were more frequent in children diagnosed earlier. The number of patients over 20 years was limited in our study, more complications may increase in additional follow-up. Continuous long-term follow up and optimal intervention are crucial for survivors of infant leukemia who are transplanted. Disclosures Kada: Bayer Yakuhin: Other: personal fees for a member of independent data monitoring committee of clinical trials, outside of the submitted work..