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. Key words: pediatric acute lymphoblastic leukemia, minimal residual disease, immunoglobulin and T cell receptor gene rearrangements -stories of clinical oncology [1,2]. In 2000, the treatment results of childhood ALL trials performed in the early 1990s by major study groups were uniformly presented. The 10-year event-free survival ranged from 77 to 85% after having achieved complete remission rates of 93% or higher [3,4,5,6]. The main cause of treatment failure, which occurs in approximately 20% of patients, is relapse arising from outgrowth of residual leukemic cells that are refractory to therapy.Over the last 2-3 decades, an intense effort has been made to develop methods to determine the degree of residual leukemia Neoplasma 57, 6, 2010 Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children, accounting for approximately 25% of all childhood cancers and about 80% of childhood leukemia. The treatment of childhood ALL is one of the true success Abbreviations: D33P -MRD positivity at day 33; D33N -MRD negativity at day 33; D78P -M...

Treatment of childhood acute lymphoblastic leukemia (ALL) according to the 1st Slovak protocol started in the Slovak Republic in 1971 in eight pediatric departments. Gradually, two other protocols were written, and 496 children were treated with these three protocols from 1971 to 1992. Since 1992, all children have been treated in three pediatric oncological departments. From 1992 to 1996, protocols for standard and high-risk ALL were developed that were used for 111 children in Bratislava, while the centres in Banska Bystrica and Košice had started to use BFM protocols. Since 1997, all patients with ALL have been treated according to ALL BFM 95, and since 2002, they have been included in the ALL IC BFM 2002 study. We evaluated treatment results in the standard arm of ALL BFM 95 and compared it with previous Slovak protocols. Rates of complete remission increased from 90.6% in the fi rst Slovak protocol to 97.1% in BFM 95; EFS and OS increased from 0.46 and 0.50 to 0.67 and 0.72, respectively. Relapse rates decreased from 42% to 20.5%. EFS was signifi cantly worse in children with leukocyte counts >100 × 10 9 /l and in the HR group in comparison to standard-and medium-risk groups. OS was also signifi cantly worse in T-cell ALL than in B-cell ALL. Death rates in the 1st complete remission decreased gradually in the Slovak protocols from 10.4% to 1.8%, but were high in BFM 95 (10.8%) due to more intensive therapy and initial unsatisfactory experiences with BFM protocols. All parameters improved in the ALL IC BFM 2002 study.

A unique case of ALL in three monozygotic triplets diagnosed at the age of 24, 27 and 37 months is described. Archived bone marrow smears were available for molecular analysis of immunoglobulin heavy chain (IGH) and IGK genes and T-cell receptor (TCR)-delta and gamma gene rearrangements. A shared IGH rearrangement was found in triplets "A" and "B", and an identical rearrangement of TCR-delta in triplets "B" and "C". These data suggest a common, monoclonal initiation of ALL in one of these three triplets, followed by dissemination of clonal progeny to the other twins via vascular anastomoses within the single, monochorionic placenta that they shared in utero. Differences in IGH rearrangements in diagnostic samples also indicates divergent subclonal evolution of the original "pre-leukaemic" clone.

No 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...