RESUMO
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 2002-2007, 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 1997-2001. 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.
RESUMO
Acute lymphoblastic leukemia is the most common form of cancer in children. The 10-year event-free survival ranged from 77 to 85% after having achieved complete remission rates of 93% or higher. The main cause of treatment failure is relapse arising from outgrowth of residual leukemic cells that are refractory to therapy. An intense effort has been made to develop methods to determine the degree of minimal residual leukemia cells present in patients considered to be in morphological remission. Because of the strong correlation between minimal residual disease (MRD) levels and risk of relapse, monitoring of MRD provides unique information regarding treatment response. The MRD monitoring based on real-time quantitative PCR detection of patient-specific immunoglobulin and T-cell receptor (Ig/TCR) gene rearrangements is currently considered to be the most reliable tool for MRD-based diagnosis in ALL. Because the significance of MRD monitoring has been strongly supported by several studies and because it has been implemented in the latest protocols, there has been a significant effort to develop MRD monitoring in the Slovak Republic since 2005. Between October 2006 and December 2009, 50 children with ALL who were treated at three Slovak centers were included in the RQ PCR MRD pilot project. A total of 40 patients with BCP-ALL ( B cell precursor ALL) and 4 patients with T ALL were analyzed for Ig/TCR rearrangement. We identified 106 different rearrangements in the 44 ALL patients analyzed. Based on MRD stratification, we identified 26 patients who were stratified into the HRG ( high risk group) (n = 3; 11.5%), IRG ( intermediate risk group) (n = 14; 54%) and SRG ) standard risk group) (n = 9; 34.5%). Morphology-based risk stratification allows the identification of most HRG patients identified also by MRD-based stratification, but fails to discriminate the IRG assigned to therapy reduction. Patients in the SRG and the IRG could profit from MRD-based risk assignment