Improved outcome for children and adolescent with acute lymphoblastic leukemia in the first decade of the 21st century: A report from the Slovak Republic

Abstract

Our aim was to analyze event-free (EFS) and overall survival (OS) among children and adolescents with acute lymphoblastic leukemia (ALL) treated with International BFM Intercontinental trial (ALL IC 2002) therapy in the Slovak Republic. In total, 280 children and adolescent age 1 to 18 years were treated with ALL IC BFM 2002 based therapy from 2002 to 2012, which was divided into two periods. During 2002During -2007, when patients were actively enrolled in the ALL IC-BFM 2002 trial, and during 2008-2012 when the trial was closed and patients were treated with the same therapy without randomization. Five-year EFS and OS rates were 79% (+/-2.6%) and 86% (+/-2.1%), respectively, similar to results obtained in the ALL-BFM 95 trial, which was the basis for ALL IC BFM 2002 therapy. The EFS (p<0.012) and OS (p<0.003) were significantly better than the prior Slovak experience in [1997][1998][1999][2000][2001]. Survival is improved in standard and intermediate risk groups, including those age 1 to 6 years, and older; with B-cell or T-cell immunophenotype, and is also excellent for those with good early response. The rate of death in induction, cumulative incidence of death in complete remission and of relapse decreased. However, outcome was suboptimal for patients in the high risk group. Current EFS and OS rates for children and adolescents with ALL in the Slovak Republic resembled those obtained in Western Europe as a result of clinical trial participation, and clinical experience acquired with intensive BFM type treatment. Key words: acute lymphoblastic leukemia, children, clinical trialThe treatment of childhood acute lymphoblastic leukemia (ALL) is one of the success stories of clinical oncology [1,2,3]. Pediatric ALL 5-year overal survival (OS) rates have improved to approximately 90% in trials conducted in North America and Western Europe with risk stratification by biological features of leukaemic cells and response to treatment and improved supportive care [4,5,6,7,8,9,10]. The outstanding outcome has been obtained in countries with highly developed health care systems and has been possible because of high enrollment in clinical trials by cooperative groups and large institutions, with the two largest being the Children's Oncology Group (COG) based in North America and the [12]. Children with ALL in Slovakia were included in the ALL IC-BFM 2002 trial, which was designed for countries inside the I-BFM study group who had achieved event-free survival (EFS) rates of at least 65%, but were not able to utilize the minimal residual disease (MRD) testing employed in recent BFM trials [11,12]. The ALL IC BFM 2002 prospective randomized international trial provided the first experience for Slovakia to participate in an international pediatric ALL treatment study. Prior to 1992, Slovakian children diagnosed with ALL and other malignancies were treated in several different children's departments using a variety of therapies. Starting in 1992, pediatric cancer therapy in Slovakia was centralized in three children's oncolo...

Clinical impact of genomic analysis in children with B-acute lymphoblastic leukemia: A pilot study in Slovakia

“…In the 1960s, less than 10% of children with ALL achieved a long-term survival. With current therapy, the chance for 5-year event-free survival and overall survival increased to almost 85% and 90%, respectively [2]. The dramatic improvement in the patient outcome was facilitated by stratification of treatment intensity based on the assessment of risk factors.…”

“…The dramatic improvement in the patient outcome was facilitated by stratification of treatment intensity based on the assessment of risk factors. These factors include clinical factors, patient response to induction therapy and cytogenetic abnormalities [1][2][3]. Patients with the greatest relapse risk receive the most aggressive treatment, and less intense regimens are given to patients at lower relapse risk.…”

“…Approximately 75% of childhood B-ALL cases harbor primary chromosomal abnormalities detectable by karyotyping, fluorescent in situ hybridization (FISH) or molecular techniques. Six major genetic subtypes, accounting for 75% B-ALL cases, are as follows: high hyperdiploidy (51-67 chromosomes per cell), ETV6-RUNX1 (TEL-AML1) and TCF3-PBX1 confer the most favorable prognosis, whereas hypodiploidy (less than 45 chromosomes per cell), BCR-ABL1, KMT2A (MLL) translocations are associated with poor prognosis [2][3][4][5]. In the remaining 25%, pediatric B-ALL patients lack abnormalities with clinical relevance for prognosis assessment.…”