Acute pediatric leukemia with KMT2A GENE alterations: an institution experience in the last 20 years

Abstract

Chromosomal rearrangements of the human KMT2A gene are associated with infant, pediatric, adult and therapy-related acute leukemia with poor prognosis. We present a retrospective study of 187 pediatric patients with KMT2A rearranged acute lymphoblastic (ALL), acute myeloblastic leukemia (AML) and therapy related leukemia (TRL) with the aims of describing clinical characteristics, KMT2A rearrangements subtypes and  patients' outcome from January 2000 to July 2021. Of the 187 patients with KMT2A rearrangements, 94 were diagnosed as ALL, 93 as AML and 5 were TRL. The median age at diagnosis was 6 months for ALL and 5 years for AML. Sex distribution (M/F) was 1/1.22 and 1/1.44 for ALL and AML, respectively. KMT2A gene involvement was detected by PCR and/or G-band/FISH. The frequency of KMT2A rearrangements in the ALL group was: KMT2A-AFF1, 55%, KMT2A-MLLT1, 23.7%, KMT2A-MLLT3, 16% and KMT2A-MLLT10, 4.4%. In the AML group, the most frequent alteration was KMT2A-MLLT3: 40%, KMT2A-MLLT10: 18%, KMT2A-MLLT11: 8%, KMT2A-AFF1 and KMT2A-MLLT1: 7%. All patients received chemotherapy and 13 ALL and 12 AML patients underwent hematopoietic stem cell transplantation (HSCT). Event free survival (EFS) was 26%, 43% (p=0.02) and overall survival (OS) 31% and 47% for ALL and AML, respectively. EFS comparing patient’s age at diagnosis was 50% vs 22% for children older and younger than 1 year (p=0.0015). EFS comparing patients with chemotherapy treatment only and those who underwent HSCT was 26% vs. 50% for the whole cohort (p=0.09); 23% vs. 46% for ALL (p=0.10) and 45% vs. 60% for AML (p=0.20). We confirm that acute leukemia patients with KMT2A rearrangements have a poor outcome, age is a good indicator of poor prognosis and better results are achieved with HSCT as therapeutic strategy.