In a retrospective study reported in the Journal of Clinical Oncology, Attarbaschi et al described outcomes in patients with noninfant childhood acute lymphoblastic leukemia (ALL) and 11q23/KMT2A rearrangements treated with chemotherapy regimens between 1995 and 2010.
Study Details
The study included data on 629 patients from 17 members of the Ponte-di-Legno Childhood ALL Working Group. Clinical and biological characteristics, early response indicted by measurable residual disease at end of induction therapy, and use of allogeneic hematopoietic stem cell transplantation (HSCT) in first remission were evaluated for potential impact on outcomes.
Key Findings
Specific 11q23/KMT2A translocation partner genes were identified in 530 patients (84.3%); the most common translocations were: t(4;11)(q21;q23) in 273 (51.5%); t(11;19)(q23;p13.3) in 106 (20.0%); t(9;11)(p21_22;q23) in 76 (14.3%); t(6;11)(q27;q23) in 20 (3.8%); and t(10;11)(p12;q23) in 14 (2.6%). Patient characteristics and rates of early response varied among subgroups, indicating large biological heterogeneity and associated differences in sensitivity to therapy.
In the entire cohort, the end of induction therapy remission rate was 93.2% and 5-year event-free survival was 69.1%; 5-year rates ranged from 41.7% among 9 patients with t(9;11)-positive T-ALL and 64.8% among 266 patients with t(4;11)-positive B-cell ALL to 91.2% among 34 patients with t(11;19)-positive T-ALL. Overall survival at 5 years in the entire cohort was 76.6%. As related by the investigators, outcomes in the entire cohort were superior to those identified among historical controls in a prior study by the Working Group.
Among 535 patients with 11q23/KMT2A-rearranged B-cell ALL, the 5-year overall survival of 76.6% was only somewhat higher than the 5-year event-free survival of 68.9%; this was partly due to a high rate of treatment-related mortality, which accounted for 24% of events. Event-free and overall survival were superior among patients treated from 2005 to 2010 vs those treated from 1995 to 2005.
Low end of induction therapy measurable residual disease was associated with improved event-free survival; poor response to induction therapy was predictive of absence of response to further treatment, higher risk of relapse, and poor event-free survival.
No improvement in event-free survival was observed with allogeneic HSCT vs chemotherapy alone among 64 vs 51 patients with t(4;11)-positive B-cell ALL (P = .10) or among 16 vs 10 patients with 11q23/KMT2A-rearranged T-ALL (P = .69).
The investigators concluded, “Compared with historical data, prognosis of patients with noninfant 11q23/KMT2A-rearranged ALL has improved, but allogeneic HSCT failed to affect outcome. Targeted therapies are needed to reduce relapse and treatment-related mortality rates.”
Andishe Attarbaschi, MD, of St. Anna Children’s Hospital, Medical University of Vienna, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Institutes of Health and National Cancer Institute, St. Baldrick’s Foundation, and American Lebanese Syrian Associated Charities. For full disclosures of the study authors, visit ascopubs.org.
