High-risk acute lymphoblastic leukemia in the ALL-MB 2002 study

Abstract

This paper presents the results for the patients with acute lymphoblastic leukemia (ALL) from the high-risk group (HRG) treated according to the ALL-MB 2002 Protocol. The registration phase of the study was performed from 15.04.2002 to 01.01.2008. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The study involved 36 departments (centers) of pediatric hematology/oncology in Russia and Belarus. One hundred and ten primary patients with ALL aged 1 to 18 years who met the criteria for high risk group, were analyzed: 29 patients with t(9;22), 11 patients with t(4;11), and 70 patients without stratifying genetic abnormalities who did not achieve remission by day 36 of induction therapy (16 patients from the standard risk group and 54 patients from the intermediate risk group, at initial). Median follow-up was 10.75 (8.6–13.8) years. First remission (CR1) was achieved in 80.9% of patients. 37.27% of patients relapsed, 51.22% of relapses were very early. The proportion of isolated bone marrow relapse was 73%, while isolated central nervous system relapses were observed in 4.55% of the cases. None of the patients developed a secondary tumor, 5.45% of patients were lost from follow-up. Only 15.7% of patients with CR1 received allogeneic hematopoietic stem cell transplantation. Only half of the patients with Ph-positive ALL received treatment with tyrosine kinase inhibitors. In total, 26.36% of patients remain in CR1. Overall and event-free survival were 32.9 ± 4.6% and 31.5 ± 4.5%, respectively. The cumulative risks of relapses and treatment-related mortality were 37.6 ± 4.3% and 20.9 ± 3.8%, respectively. There were no significant difference in the initial parameters and responses to therapy between the subgroups of patients. Overall and event-free survival were the highest in patients with ALL with t(4;11): 54.5 ± 15% and 45.5 ± 15%, respectively. The lowest overall and event-free survival were observed in the subgroup of patients without stratifying anomalies who did not achieve remission on day 36: 29.1 ± 5.6% and 27.1 ± 5.3%, respectively. The cumulative risk of relapse was the highest in patients who did not respond to induction therapy (42.9 ± 5.2%). The cumulative risk of treatment-related mortality was the highest in patients with Ph-positive ALL (31.0 ± 8.6%). The 5-year overall survival of patients with ALL relapse after high-risk therapy was extremely low – 7.7% (95% confidence interval 0–16.1), median overall survival after relapse in this group was only 187 days. This indicates that the options for second-line therapy of high-risk patients were severely limited at the time of ALL-MB 2002 study, because they included only chemotherapeutic strategies.