Translocation t(12;21)(p13;q22)/ETV6::RUNX1 is among the most common genetic aberrations in pediatric B-cell precursor acute lymphoblastic leukekian (BCP-ALL). This translocation is often combined with ETV6 and/or RUNX1 copy number variations. Fluorescence in situ hybridization (FISH) technique, which is widely used to reveal the presence of t(12;21)(p13;q22), also allows the detection of these additional genetic aberrations (FISH patterns). The aim of this study was to provide detailed characteristics of FISH patterns in patients with BCP-ALL and the t(12;21)(p13;q22)/ETV6::RUNX1 translocation. In our study we enrolled 241 patients with t(12;21)-positive ALL who had undergone testing with a dual-color double-fusion FISH assay between 2008 and 2023. This study was approved by the Independent Ethics Committee and the Academic Council of the Research Institute of Medical Cell Technologies (Ekaterinburg). A single FISH pattern (monoclonal cases) was identified in 200 patients (83.0%), 2 or more patterns (polyclonal cases) were detected in 41 (17.0%) patients. The majority of polyclonal cases (n = 39; 95.1%) exhibited 2 patterns. The most common secondary genetic alteration was ETV6 deletion (n = 105; 43.5%). Less common aberrations included an additional copy of RUNX1 (n = 97; 40.2%), a combination of ETV6 deletion and an additional copy of RUNX1 (n = 27; 11.2%), and an additional copy of ETV6 (n = 5; 2.0%). The number of the patients with one FISH pattern that did not contain any additional genetic aberrations as a result of a reciprocal translocation (2F1G1R) was relatively small (n = 35; 17.5%). We identified 5 prognostically unfavorable FISH patterns associated with a high risk of relapse. These included cases with simultaneous presence of ETV6 and RUNX1 additional copies (pattern 2F2G2R), isolated additional copies of RUNX1 (pattern 2F2R-3F2R) or ETV6 (pattern 1F1G2R-2F2G4R), a partial deletion of ETV6 (pattern 2F1Gdim1R) and a non-reciprocal translocation of t(12;21) (pattern 1F1R-1F1G1R). Grouping these unfavorable prognostic FISH patterns together made it possible to predict 6 (46%) out of 13 relapses that occurred in the patients during the study period. It is important to highlight that the number of the patients with unfavorable FISH patterns and initial leukocytosis of > 30 × 109 leukocytes/L did not differ significantly from the rest of the group. Another important observation was that the patients with prognostically unfavorable FISH patterns responded well to induction therapy, as assessed both by cytological examination of blood and bone marrow smears on days 8, 15, and 36 of therapy and by MRD response at the end of induction therapy according to the ALL-MB 2015 protocol. A comparison of FISH patterns detected at initial diagnosis and at relapse showed that only 6 (50%) out of 12 cases who had undergone FISH testing at both time points remained stable. In conclusion, BCP-ALL with the translocation t(12;21)(p13;q22)/ETV6::RUNX1 was characterized by a vast variety of secondary genetic aberrations detected by FISH, the most prevalent of which was ETV6 deletion. A group of unfavorable FISH patterns identified in our study warrants further investigation in a larger cohort of ALL patients for their possible re-stratification so that they could receive more intensive treatment.
The achievement of remission at the end of induction (EOI) chemotherapy in patients with acute lymphoblastic leukemia (ALL) is the key parameter of treatment effectiveness evaluation. The aim of the study – defining complete remission by multicolor flow cytometry (MFC) and bone marrow (BM) cytomorphology (CM) at the EOI chemotherapy in children with B-lineage ALL. 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. The study included patients of “ALL-MB 2008” and “ALL-MB 2015” trials for whom minimal residual disease (MRD) was evaluated by MFC at the EOI simultaneously with CM BM investigation. Less than 5% blasts in BM and MRD < 1% were established as the remission achievement criteria for CM and MFC respectively. The study group included 1498 children aged from 1 to 18 years (median age was 4 years and 11 months) with B-cell precursor ALL. The overall concordance of MFC and CM was found to be 96.1% (1440 of 1498 patients). In 36 (2.4%) children with MRD ≥ 1%, M1 BM status was observed. In contrast, in 22 (1.5%) patients with M2/M3 BM status by CM, MRD value was below 1%. Treatment outcome was analyzed in 522 patients of “ALL-MB 2008” trial. Children with M2/M3 BM, as well as with MRD ≥ 1% demonstrated dramatically inferior outcome, in comparison to those who achieved remission. The presence of at least one of the mentioned criteria (M2/M3 status by CM or MRD ≥ 1% by MFC) defined a group of 23 (4.4%) patients with very low event-free survival (34.9%, standard error 11.0%) and very high cumulative incidence of relapse (56.4%, standard error 12.0%). For the evaluation of remission achievement, MFC and CM should be applied simultaneously at the EOI. High leukemic burden found by any of these methods is the clear definition of induction failure. MRD detection at the EOI should be implemented in any modern treatment protocol as an obligatory stage of treatment response monitoring and final risk group stratification. Considering the crucial importance of the MRD detection results, this study must be performed only in the reference laboratories of the study groups.
The purpose of this work was evaluation of prognostic significance of 11q23/KMT2A rearrangements in infants (aged under 365 days) with B-cell precursor acute lymphoblastic leukemia (ALL) enrolled in Russian-Belarus multicenter trial MLLBaby. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Research Institute of Medical Cell Technologies (Ekaterinburg). Various 11q23/KMT2A rearrangements were revealed in 100 (72%) of 139 patients. Event-free survival (EFS) in the intermediate risk group of MLL-Baby trial was 35.1% (standard error (SE) 6.9%), in the high risk group – 38.3% (SE 7.1%) (p = 0.941). The most unfavorable prognosis had infants with translocation t(9;11)/KMT2A-MLLT3: EFS 18.8% (SE 9.8%), cumulative incidence of relapse (CIR) 75.0% (SE 9.7%). Intermediate results were obtained in patients with translocations t(4;11)/KMT2A-AFF1 and t(11;19)/KMT2A-MLLT1: EFS 36.9% (SE 7,2%) and 32,7% (SE 10.4%), respectively; CIR 46.3% (SE 7.8%) and 50.9% (SE 12.3%). The most favorable treatment outcome was achieved in infants carrying translocation t(10;11)(p12;q23)/KMT2A-MLLT10: EFS 83.3% (SE 15.2%), CIR 0,0%. In the multivariate analysis unfavorable outcome of KMT2A-rearranged infant ALL was associated with initial CNS involvement (p = 0.020), initial white blood cell count higher than 300 × 109 /L (p = 0.028), more than 5% blast cells on day 15 in bone marrow (p = 0.012) and presence of translocation t(11;19)/KMT2A-MLLT1 (p = 0.012).
The purpose of this work was evaluation of prognostic significance of 11q23/KMT2A rearrangements in infants (aged under 365 days) with B-cell precursor acute lymphoblastic leukemia (ALL) enrolled in Russian-Belarus multicenter trial MLLBaby. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Research Institute of Medical Cell Technologies (Ekaterinburg). Various 11q23/KMT2A rearrangements were revealed in 100 (72%) of 139 patients. Event-free survival (EFS) in the intermediate risk group of MLL-Baby trial was 35.1% (standard error (SE) 6.9%), in the high risk group – 38.3% (SE 7.1%) (p = 0.941). The most unfavorable prognosis had infants with translocation t(9;11)/KMT2A-MLLT3: EFS 18.8% (SE 9.8%), cumulative incidence of relapse (CIR) 75.0% (SE 9.7%). Intermediate results were obtained in patients with translocations t(4;11)/KMT2A-AFF1 and t(11;19)/KMT2A-MLLT1: EFS 36.9% (SE 7,2%) and 32,7% (SE 10.4%), respectively; CIR 46.3% (SE 7.8%) and 50.9% (SE 12.3%). The most favorable treatment outcome was achieved in infants carrying translocation t(10;11)(p12;q23)/KMT2A-MLLT10: EFS 83.3% (SE 15.2%), CIR 0,0%. In the multivariate analysis unfavorable outcome of KMT2A-rearranged infant ALL was associated with initial CNS involvement (p = 0.020), initial white blood cell count higher than 300 × 109 /L (p = 0.028), more than 5% blast cells on day 15 in bone marrow (p = 0.012) and presence of translocation t(11;19)/KMT2A-MLLT1 (p = 0.012).
Aim. The objective of the study was searching for surface antigen expression that could predict presence of translocation t(12;21)(p13;q22)/ ETV6-RUNX1 in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Results. ETV6-RUNX1 fusion gene transcript was revealed in 72 (21.1%) out of 341 children with BCP-ALL. Leukemic blast cells in ETV6-RUNX1 — positive patients more frequently had high CD10 expression, myeloid markers co-expression, including CD13, CD33, CD117, and absence of CD20 than in ETV6-RUNX1 — negative ones. Nevertheless diagnostic test performance characteristics of each single parameter was not strong enough for predicting the presence of translocation t(12;21)(p13;q22)/ETV6-RUNX1. On the second step of analysis we used various combinations of the above mentioned markers. The highest diagnostic test performance parameters were obtained in case of combination of high CD117 and heterogeneous CD34 expressions. Specificity of this combination was 0.996 (95% CI 0.989-1.000), positive predictive value 0.947 (95% CI 0.847- 1.000), positive likelihood ratio 67.250 (95% CI 9.130-495.348), while negative likelihood ratio was 0.752 (95% CI 0.659-0.860). Conclusion. Thus, combination of CD34 heterogeneous expression and CD117 expression is highly specific for translocation t(12;21)(p13;q22)/ ETV6-RUNX1. However this combination had limited applicability, because it revealed in 25.0% percent of patients only.
The objective of the study was searching for surface antigen expression that could predict presence of translocation t(12;21)(p13;q22)/ETV6RUNX1 in pediatric B-cell precursor acute lymphoblastic leukemia patients.Results . ETV6-RUNX1 fusion gene transcript was revealed in 118 (22.4 %) out of 526 children with B-cell precursor acute lymphoblastic leukemia. Leukemic blast cells in ETV6-RUNX1-positive patients more frequently had high CD10 expression, myeloid markers co-expression , including CD13, CD33, CD117, and absence of CD20 than in ETV6-RUNX1-negative ones. Nevertheless diagnostic test performance characteristics of each single parameter was not strong enough for predicting the presence of translocation t(12;21)(p13;q22)/ETV6-RUNX1.Conclusion . Thus application of conventional set of immunological markers does not allow reliable distinguishing this patients’ subgroup. However antibodies panel enlargement, high degree of flow cytometry standardization and additional analytical methods can potentially improve applicability of antigen profile analysis for separation of patients with translocation t(12;21)(p13;q22)/ETV6-RUNX1.
Introduction. Translocation t(12;21)(p13;q22) is one of the most common structural genetic abnormalities in childhood acute lymphoblastic leukemia (ALL). It cannot be detected by conventional G-banding, so a reverse-transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization are used for this purpose.The aim of the study was to evaluate the prognostic significance of qualitative and quantitative detection of ETV6-RUNX1 fusion gene transcript at various time points in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients.Materials and methods. ETV6-RUNX1 fusion gene transcript was revealed by both reverse-transcriptase PCR and quantitative real-time PCR (RQ-PCR) in 34 out of 166 (20.5 %) children with BCP-ALL. Qualitative ETV6-RUNX1-positivity at days 36 and 85 led to unfavorable outcome (lower event-free survival –EFS and higher cumulative incidence of relapse – CIR). While ETV6-RUNX1 status at day 15 did not allow to divide patients with different outcomes. By ROC curve analysis we determined threshold levels (TL) for ETV6-RUNX1/ABL1 ratio at days 0, 15, 36 and 85. Afterwards we adjusted obtained results to 10-fold scale.Results. So practically applicable TL were as follows 500.0 %, 1 %, 0.1 % и 0.01 % for days 0, 15, 36 and 85, respectively. EFS and CIR were both worse in patients with ETV6-RUNX1/ABL1 ratio equal or above defined TL. Moreover, initial ratio ≥500,0 % corresponded to delayed blast clearance at days 15 and 36. We showed good qualitative (84.8 %) and quantitative (R2 = 0.953) concordance between ETV6-RUNX1/ABL1 ratio and MRD data obtained by flow cytometry at days 15, 36, 85. Of note, defined TL for ETV6-RUNX1/ABL1 at days 15, 36, 85 were equal to prognostically important levels for flow cytometry MRD.Conclusion. Thus, qualitative detection and quantitative value of ETV6-RUNX1 fusion gene transcript showed prognostic significance in the course of treatment in children with BCP-ALL. Based on these results we propose standardization approaches for Moscow – Berlin ALL study group.
The purpose of the current work was the estimation of prognostic significance of cytogenetic and molecular markers, assessed by multiplex ligation-dependent probe amplification (MLPA) in 142 cases of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Good-risk genetic (GEN-GR) group consisted of 114 patients carrying either ETV6-RUNX1 or high hyperdiploidy together with normal copy-number status for all 8 genes (IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A/2B and PAR1) or isolated deletions affecting ETV6/ PAX5/BTG1 and ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/2B. All other patients (n = 28) were classified to genetic poor risk (GEN-PR) group. GEN-PR features were older age (p = 0.015), stratification to high-risk group of ALL-MB 2008 protocol (p = 0.001), higher initial WBC (p = 0.008), M3 marrow status on day 15 (p = 0.002) and lack of remission on day 36 (p = 0.039). GEN-PR patients had statistically significant lower event-free survival (EFS) (0.59 ± 0.11 vs 0.88 ± 0.03; p = 0.0008), overall survival (OS) (0.63 ± 0.15 vs 0.93 ± 0.02; p = 0.0050) and higher cumulative incidence of relapse (CIR) (0.38 ± 0.12 и 0.06 ± 0.02; p < 0.0001) in comparison to GEN-GR patients. Genetic risk group stratification retained its negative prognostic value in multivariate analysis affecting EFS (hazard ratio (HR) – 2.659; 95 % CI 1.047–6.755; p = 0.040) and CIR (HR – 3.864; 95 % CI 1.226–12.183; p = 0.021), nut did not influenced to OS (HR – 1.479; 95 % CI 0.356–6.139; p = 0.590). There was no prognostic significance of genetic risk group classifier in the “B-other ALL” group. Majority of unfavorable events (9 out of 10) and relapse (8 out of 9) in GEN-PR patients were revealed in case of IKZF1 deletion co-occurrence. Moreover all 15 patients carrying IKZF1 deletions were stratified to GEN-PR group. So when we added IKZF1 deletion as extra variable in the multivariate analysis genetic risk group classification lost its prognostic significance on EFS (HR – 0.696; 95 % CI 0.086–5.636; p = 0,735), and CIR (HR – 0.511; 95 % CI 0.053–4.924; p = 0.561), while IKZF1 deletion remained its prognostic value both to risk of unfavorable event (HR – 4.292; 95 % CI 1.521–12.911; p = 0.006) and risk of relapse (HR – 9.163; 95 % CI 3.131–26.815; p < 0.001). Thus, combination of cytogenetic risk group and MLPA markers did not bring any advantage over detection of isolated IKZF1 deletion for the estimation of prognosis in pediatric BCP-ALL.
The relapse of acute lymphoblastic leukemia (ALL) in children is still a difficult task. This is due both to the difficulties of achieving a second remission and to the problems of organizing allogeneic bone marrow transplantation (BMT) in those patients who need it. The standard approach is the use of second-line drugs in the regime of high-dosage chemotherapy blocks, but the response rate for this treatment in patients with early relapses remains low and the response time is short. Recently, new drugs with different mechanisms of action have appeared that can give an opportunity for a full remission. The organization of a multicentre study on anti-relapse therapy in the Russian Federation is an urgent task, the solution of which can help in studying new approaches to therapy and in the organization of BMT logistics. This article presents the results of a pilot multicentre study on the treatment of relapses of ALL in children in the Russian Federation. The effectiveness of standard therapy for a group with late relapses and the efficacy and toxicity of interventional blocks with the use of bortezomib, clofarabine, nelarabine are presented.
This article represents results of work of Center of pediatric oncology and hematology of Regional pediatric clinical hospital № 1 of Yekaterinburg on Hematopoietic stem cell transplantation (HSCT) during the period 2006–2016. One hundred seventeen HSCT performed during this time including 70 autologous, 33 allogenic, 14 haploidentical at patients with solid tumors (n = 55), acute leukemias (n = 27), lymphomas (n = 9), non-malignant diseases (n = 11). Results of treatment depending on type of disease and HSCT were shown. It was indicated that presence of minimal residual disease (MRD) before HSCT in case of leukemia and neuroblastoma was indicated as negative prognosis. Possible way of treatment of persistent MRD after HSCT with the help of blinatumomab and donor lymphocytes infusion showed.
We assessed the prognostic significance of IKZF1 gene deletions in 141 pediatric patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) on Russian multicenter trial in pediatric clinics of Ekaterinburg and Orenburg. IKZF1 deletions were estimated by multiplex ligation-dependent probe amplification. IKZF1 deletions were revealed in 15 (10.6 %) patients. IKZF1 deletions were associated with age older than 10 years (p = 0.007), initial white blood cell count higher than 30 × 109/l (p = 0.003), t(9;22)(q34.q11) (p = 0.003) and delayed blast clearance: М3 status of bone marrow at day 15 of remission induction (p = 0.003), lack of hematological remission at day 36 (p < 0.001) and high levels of minimal residual disease at days 15, 36 and 85 (p = 0.014; p < 0.001; p = 0.001 correspondingly). Patients with IKZF1 deletions had significantly lower event-free survival (EFS) (0.30 ± 0.15 vs 0.89 ± 0.03; p < 0.001) and overall survival (OS) (0.44 ± 0.19 vs 0.93 ± 0.02; p < 0.001), while cumulative incidence of relapse was higher (0.67 ± 0.18 vs 0.07 ± 0.02; p < 0.001). In the multivariate analysis IKZF1 deletions were associated with decreased EFS (hazard ratio (HR) 4.755; 95 % confidence interval (CI) 1.856–12.185; p = 0.001), and OS (HR 4.208; 95 % CI 1.322–13.393; p = 0.015), but increased relapse risk (HR 9,083; 95 % CI 3.119–26.451; p < 0.001). IKZF1 deletions retained their prognostic significance in the intermediate risk group patients (p < 0.001), but not in standard or high-risk groups. Majority of IKZF1 deletions – 12 (80 %) of 15 – were revealed in the “B-other” group (n = 83). In this cohort of patients IKZF1 deletions led to inferior EFS (HR 6.172; 95 % CI 1.834–20.767; p = 0.003) and higher relapse rate (HR 16.303; 95 % CI 3.324–79.965; p = 0.015). Thus, our results showed that IKZF1 deletions are independent risk factor in BCP-ALL patients.
One of the main risk-factors of acute lymphoblastic leukemia (ALL) is age. The most favorable age group is children from 2 to 9 years old, and the adolescents and young adults have the worst prognosis. Treatment of ALL at adolescents and young adults is a unique problem of modern hematology now. This work presents the analysis of 368 cases of patients with primary ALL 15–18 years old, which were registered in the database of Russian-Belarussian group from April 2002 to November 2014. The aim of the analysis was the estimation of effectiveness of different generations of protocol for adolescents and prognostic significance of different factors to reveal the ways of future therapy optimizing in this age group. Event-free survival of adolescents 15–18 years old according our study was 56 ± 5 % in ALL-MB-2002 study and 57 ± 6 % in ALL-MB-2008 study. We did not received any differences in survival based on immunophenotype of blast cells. But the risk group analysis showed the worst results at patients with ALL from pre-B-precursor cells of high risk. No difference was revealed according the gender. One of the general problems remains high toxicity of therapy at patients of this age group. Treatment related mortality (TRM) was 13.2 and 12 % at ALL-MB-2002 and ALL-MB-2008 accordingly. Main cause of deaths remains infection.
Aim. To study characteristics of 11q23 involvement, age-specific differences in the incidence of these chromosomal markers in acute myeloid leukemias (AML) in children, and to determine their prognostic significance in patients treated according to the protocols applied in leading Russian pediatric hematological clinics. Methods. The chromosomal analysis of bone marrow and peripheral blood cells has been performed prior to initiation of treatment in 395 children with primary AML aged from 0 to 16 years. The patients were treated in pediatric hematological clinics of Moscow and Moscow Region and in Yekaterinburg District Children’s Hospital No. 1. Clinical outcomes of 300 followed-up pediatric patients treated with similar modern therapy protocols were analyzed to evaluate the prognostic impact of 11q23/MLL abnormalities. To determine the incidence of 11q23/MLL rearrangements in AML of different age groups, we examined not only children, but also adult patients (n = 212). Results. In AML, the frequency of changes in the 11q23 region exceeded 40 % in children aged from 0 to 2 years. The frequency decrease with age and in patients over 40 years it was only 2 %. Significant heterogeneity of changes in karyotypes with 11q23/MLL rearrangements was observed: both various translocations with different regions of other chromosomes, and 11q23 deletions were detected. In addition, a great variability of numerical and structural additional chromosomal abnormalities was observed. The 10-year relapse-free survival rates (30.4 ± 6.7 %) and overall survival rates (35.1 ± 7.0 %) in AML with changes in the 11q23 region (n = 61) were significantly lower than those in patients from the intermediate risk group (n = 103): 48.9 ± 5.8 % and 43.8 ± 7.5 %, respectively (p = 0.035). The data are close to those in the high-risk group (n = 44): 35.9 ± 8.1 % and 38.3 ± 7.6 %, respectively. The study failed to confirm the published data that t(9;11) is a more favorable prognostic factor, and that t(6;11) and t(10;11) are less favorable ones than all other 11q23 translocations. Our results did not confirm a negative prognostic effect of additional chromosome abnormalities associated with 11q23 rearrangements. Conclusion. Pediatric AML patients with 11q23 abnormalities should be included in a high-risk group if therapy is performed according protocols applied in leading hematological centers of Russia.
Aim. To study characteristics of 11q23 involvement, agespecific differences in the incidence of these chromosomal markers in acute myeloid leukemias (AML) in children, and to determine their prognostic significance in patients treated according to the protocols applied in leading Russian pediatric hematological clinics. Methods. The chromosomal analysis of bone marrow and peripheral blood cells has been performed prior to initiation of treatment in 395 children with primary AML aged from 0 to 16 years. The patients were treated in pediatric hematological clinics of Moscow and Moscow Region and in Yekaterinburg District Children's Hospital No. 1. Clinical outcomes of 300 followed-up pediatric patients treated with similar modern therapy protocols were analyzed to evaluate the prognostic impact of 11q23/MLL abnormalities. To determine the incidence of 11q23/MLL rearrangements in AML of different age groups, we examined not only children, but also adult patients (n = 212). Results. In AML, the frequency of changes in the 11q23 region exceeded 40 % in children aged from 0 to 2 years. The frequency decrease with age and in patients over 40 years it was only 2 %. Significant heterogeneity of changes in karyotypes with 11q23/MLL rearrangements was observed: both various translocations with different regions of other chromosomes, and 11q23 deletions were detected. In addition, a great variability of numerical and structural additional chromosomal abnormalities was observed. The 10-year relapse-free survival rates (30.4 ± 6.7 %) and overall survival rates (35.1 ± 7.0 %) in AML with changes in the 11q23 region (n = 61) were significantly lower than those in patients from the intermediate risk group (n = 103): 48.9 ± 5.8 % and 43.8 ± 7.5 %, respectively (p = 0.035). The data are close to those in the high-risk group (n = 44): 35.9 ± 8.1 % and 38.3 ± 7.6 %, respectively. The study failed to confirm the published data that t(9; 11) is a more favorable prognostic factor, and that t(6; 11) and t(10; 11) are less favorable ones than all other 11q23 translocations. Our results did not confirm a negative prognostic effect of additional chromosome abnormalities associated with 11q23 rearrangements. Conclusion. Pediatric AML patients with 11q23 abnormalities should be included in a high-risk group if therapy is performed according protocols applied in leading hematological centers of Russia.
T-cell acute lymphoblastic leukemia (T-ALL) is a tumor developing as a result of malignant transformation of precursor T-cells. Despite the fact that T-ALL is responsible for about 10-15% of all ALL cases in children, it is essential to separate T-ALL in a special subgroup, as a nosological entity by the tumor biology, poor clinical outcome and resistance to therapy. We analyze the results of treatment of 644 patients with T-ALL, registered in the data base of the Russian-Byelorussian Research Group over 24 years of its work. The initial characteristics of the patients, responses to therapy, prognostic factors, and efficacy of various therapeutic options are analyzed.