Page 199 - Haematologica May 2022

Letters to the Editor
AB
CD
Figure 1. Kaplan-Meier survival curves for infants with KMT2A-germline leukemia. (A) Event-free survival (EFS) and overall survival (OS) for the standard risk group, KMT2A-germline. (B) EFS was lower for males vs. females. (C) There were no differences in EFS for infants < vs. ≥6 months at diagnosis or (D) with white blood cell (WBC) count < vs. ≥50,000/μL at diagnosis.
of the cytogenetic findings in KMT2A-g cases could not be determined, given the sample size and rarity of events. The most common reported toxicities were infectious, gastrointestinal, metabolism/nutrition disorders and neu- tropenia. Grade 3 or 4 infections were reported for 20% or greater of infants during each chemotherapy course and were observed in approximately 40% of infants dur- ing each of the continuation phases (Online Supplementary Table S3). Gastrointestinal toxicities were reported most often in the induction intensification and consolidation phases, the two phases containing high-dose methotrex- ate. Neurologic, respiratory, skin, cardiac, and vascular toxicities were less commonly reported. The toxicities were comparable to those observed in prior infant ALL trials, with notably fewer toxic deaths than P9407, which
resulted in five deaths as first events.1,3,5
The high dose intensity of AALL0631, similar to that of
P9407, and the extended duration of AALL0631 therapy may both have contributed to the observed excellent out- comes for infants with KMT2A-g. AALL0631, in compar- ison to the standard arm of the contemporary Interfant- 06 trial, gave considerably higher doses of chemotherapy. Considering age-based dose reductions in Interfant-06, the differences in cumulative chemotherapy doses were greatest in the youngest infants. Though well tolerated, the chemotherapy intensity of AALL0631 is also higher than that given to older children with KMT2A-g ALL on COG trials. The optimal therapy that will minimize tox- icity risks and achieve superior survival for this very rare subset of pediatric ALL patients has yet to be defined. Future trials could consider the incorporation of targeted
immunotherapy agents and prioritize the identification of prognostic factors that will enable some infants with KMT2A-g ALL to be treated less intensively.
Erin M. Guest,1 John A. Kairalla,2 Joanne M. Hilden,3 ZoAnn E. Dreyer,4 Andrew J. Carroll,5 Nyla A. Heerema,6 Cindy Y. Wang,2 Meenakshi Devidas,7 Lia Gore,3 Wanda L. Salzer,8 Naomi J. Winick,9 William L. Carroll,10 Elizabeth A. Raetz,10 Michael Borowitz,11 Mignon L. Loh,12 Stephen P. Hunger13 and Patrick A. Brown14
1Division of Hematology/Oncology/Blood and Marrow Transplantation, Children’s Mercy Kansas City, Kansas City, MO; 2Department of Biostatistics, Colleges of Medicine, Public Health & Health Professions, University of Florida, Gainesville, FL; 3Center for Cancer and Blood Disorders, Children’s Hospital Colorado, Aurora, CO; 4Texas Children’s Hospital, Houston, TX; 5Department of Genetics, University of Alabama at Birmingham, Birmingham, AL; 6The Ohio State University Comprehensive Cancer Center, Columbus, OH; 7Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN; 8U.S. Army Medical Research and Materiel Command, Fort Detrick, MD; 9Division of Pediatric Hematology/Oncology, University of Texas Southwestern School of Medicine, Dallas, TX; 10Department of Pediatrics and Perlmutter Cancer Center, NYU Langone Health, New York, NY; 11Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD; 12Department of Pediatrics, Benioff Children's Hospital in the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; 13Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of
haematologica | 2022; 107(5)
1207