Search

Aim. The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy. Materials and methods. All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was administered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients. Results. From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34±8% vs 8±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51±10%, 50±10% and 39,1±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported. Conclusion. The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established during controlled clinical trials.

Aim. To determine predictors for decision-making on a differential approach to choosing glucocorticosteroids (GCS) for children and adolescents with acute lymphoblastic leukemia (ALL). Subjects and methods. The analysis covered 1064 primary patients aged to 1 to 18 years with ALL who had been registered at the clinics of Russia and Belorussia in April 2002 to November 2006. Before induction therapy, the patients were randomized into a dexamethasone (DEXA) 6 mg/m2 group (n=539) and a methylprednisolone (MePRED) 60 mg/m2 one (n=525). Results. The entire group showed no statistically significant differences in survival rates between the patients receiving DEXA or MePRED. However, an analysis of age groups revealed the benefits of DEXA in children younger than 14 years (the event-free survival (EFS) was 76±2 and 71±2%, respectively (p=0.048); the overall survival (OS) was 81±2 and 77±2%, respectively (р=0.046); therapy-induced mortality was 6.4% (DEXA) and11.1% (MePRED) (р=0.014); the rate of isolated extramedullary relapses was 1.5% (DEXA) and 4.4% (MePRED) ( р=0.009). At the same time, EFS and OS in 14-to-18-year-old adolescents were statistically significantly higher than in those who used MePRED (EFS, 65±6 and 52±6%, respectively (р=0.087); OS, 72±6 and 61±6%, respectively; (р=0.17). Conclusion. The findings suggest that it is possible that the choice of a GCS for ALL therapy must be also based on a patient’s age. There is a need for further studies of this matter in prospective randomized multicenter trials in children and adolescents.

Aim. To evaluate the efficiency of the original ALL-MB-2002 protocol within the multicenter study of treatment of acute lymphoblastic leukemia (ALL) in children. Subjects and methods. A total of 1873 primary patients with ALL aged 1 to 18 years, of whom 1544 patients were enrolled in this study, were notified at 36 clinics of Russia and Belarus from April 15, 2002, to January 1, 2008. Results. With the median observation of 4.12 years, 7-year event-free survival (EFS) was 73±13%; overall survival (OS) 78±2%; relapse-free survival 82±1%. The rates of EFS and OS were equal and amounted to 76±2 and 80±2% in the standard-risk group (SRG) and intermediate-risk group (ImRG), respectively. In the high-risk group (HRG) patients, EFS and OS were as high as 30±6 and 37±6%, respectively. The frequency of relapses with central nervous system lesion was as much as 4.7% in all the patients, 6-year cumulative risk for isolated neurorecurrences being 2.5% in the SRG patients. Adolescents, patients with the baseline leukocytosis (more than 100109/l), and those with a splenic size of over 4 cm or more from the costal arch margin had substantially worse survival rates. A poor early response to therapy (on induction days 8 and 15) was also associated with its lower efficiency. Conclusion. Despite a considerable rise in the number of centers and a slight increase in the intensity of therapy, the results of the new ALL-MB-2002 protocol are as minimum equivalents obtained in the use of the previous ALL-MB-91 protocol. A significant improvement in the overall results of therapy and a reduction in the cumulative risk for isolated neurorecurrences were noted in the ImRG patients.

Проанализирована значимость прогностических факторов эффективности терапии у детей с острым лимфобластным лейкозом (ОЛЛ), получающих терапию по протоколу ALL-MB-2002, в зависимости от группы риска. В исследование были включены 1544 первичных больных ОЛЛ в возрасте от 1 года до 18 лет, получавших лечение в 36 клиниках России и Беларуси в период с 15 апреля 2002 г. до 1 января 2008 г. Из 1544 больных, включенных в анализ, пациенты группы стандартного риска (SRG) составили 69,2 %, промежуточного риска (ImRG) — 24,5 % и 6,3 % пациентов были отнесены к группе высокого риска. Анализ, проведенный у пациентов SRG, продемонстрировал резкие различия в выживаемости между отдельными подгруппами больных. Выявлены достоверные различия в показателях выживаемости пациентов в зависимости от возраста (старше и младше 10 лет), инициального лейкоцитоза (более и менее 30 × 10 9 /л), инициального пальпаторного увеличения селезенки (более и менее 4 см из-под края реберной дуги) и параметров раннего ответа на терапию (8-й и 15-й день). При ретроспективном определении больных, относящихся к SRG, с использованием новых критериев (инициальный лейкоцитоз

The paper presents the results of a multicenter randomized study of two-dose COLI-ASP regimens in therapy of consolidation of standard risk-group (SRG) children and adolescents with acute lymphoblastic leukemia (ALL) treated by the ALL-MB-2002 protocol. The principal aim of the study was to elucidate whether the dose of COLI-ASP might be reduced without losing the efficiency of therapy. The analysis covered primary ALL patients notified at 36 clinics of Russia and Belarus, enrolled for the study in the period of May 1, 2002, to October 10, 2006. Out of 819 patients to be examined, 414 received COLI-ASP in a dose of 10,000 U/m2 (a control group), and 405 children took it in a dose of 5,000 U/m2 (a study group). No statistically significant differences were found between the patients in gender, age, baseline leukocytosis, and spleen size. The study showed no statistically and clinically significant differences in event-free, overall, and relapse-free survival (EFS, OS, and RFS, respectively) and relapse rates with the use of two-dose COLI-ASP regimens. However, in the control group, the death rate in remission was twice greater than that in the study group (p = 0.02). Detailed analysis of the outcomes of therapy in some subgroups revealed no differences between the control and study groups. The Cox multiple regression analysis has indicated that the factors influencing EFS and RFS are the baseline sizes of the spleen, baseline leukocytosis, age, and a response to treatment in the period of induction, rather than the dose of E. coli asparaginase. The authors have also found that among the SRG patients, there is a subgroup of patients without risk factors, in whom the reduction in the COLI-ASP dose may substantially increase survival rates, by lowering toxicity and mortality in remission.

Therapy results of 61 patients (children and adolescents, 2—17 years of age; a median — 8.76 years) with B-cells non-Hodgkin lymphomas III—IV stage and B-cell acute leukemia (B-NHL/B-ALL), treating according to protocol with polichemotherapy and monoclonal antibodies against B-cell receptor CD20 — rituximab (Mabthera, Hoffmann La Roche) applications, are presented. The protocol consist of cytoreductive phase and 6 polychemotherapy courses, similar to original protocol B-NHL-BFM 90, with exception of decreasing methotrexate dosage in 2 first courses from 5 to 1 g/m2/24 hours. Rituximab — 375 mg/m2 IV — in Day 0 first 4 courses was given.Four patients have died within first 3 weeks of therapy, 2 were primary refractory patients and 55 patients have achieved complete remissions. There was no case of remission death; relapse has developed only at one patient (neuroleukemia in patient with Burkitt lymphoma). 54 patients (88%) are in continuous complete remission. Overall and event-free survival rate were 0,90±0,04 with median follow-up after therapy ending 34 months (12—53 months). Authors discuss tactics of such combined therapy, features of remission registration, considering that at third of patients, residual mass was long-term detected, and for which assessment besides CT/MRT a positron-emission tomography (PET) and/or a repeated biopsy were done. Also it is possible to conclude that with use of target therapy chemotherapy intensity of such tumors can be reduced. Authors concluded that in cases of target therapy efficacy criteria should be modified, and it is necessary to use as much as possible informative technique to remission control (PET, minimal residual disease assessment with use of molecular-genetic methods).

Early therapy response is one of the major prognostic factors influencing an outcome of acute lymphoblastic leukemia (ALL). The purpose of the given work was to define a time point (TP) of fusion gene transcript (FGt) monitoring by reverse-transcriptase PCR that clearly predicts outcome in infants with MLL-rearranged ALL, enrolled onto MLL-Baby protocol. Molecular remission (cMR) was defined as absence of FGt at nested RT-PCR with sensitivity 1 × 10–4 or higher confirmed with negative result in the following time point (ТP). Detection of FGt in bone marrow (BM) was performed by qualitative nested RT-PCR on 15th , 36th and 43th days of therapy (TP1-TP3) and also during consolidation/intensification (ТP4-ТP9). Retrospectively, patients were divided into two groups. First group included 14 patients who achieved cMR by TP4, where two relapses occurred. The second group consisted of four MLL-AF4-positive patients, who did not achieve cMR by TP4. In this group there were 3 relapses. Number of relapses was significantly higher in the second group (odds ratio 18.00; 95 % CI: 1.19-271.47; p = 0.044). 6-years event-free survival (EFS) in the first group was 0.84 ± 0.10, in the second group — 0.25 ± 0.21 (p = 0.023). Cumulative incidence of relapse in the first group was 0.15 ± 0.01, in the second group 0.75 ± 0.08 (p = 0.022). Time of cMR achievement did not correlate with any known prognostic factors including therapy response on day 8, 15 and 36. Slow achievement of cMR corresponds to poor outcome in infant ALL with MLL rearrangements. Persistence of FGt at TP4 allows defining patients with high risk of relapse.

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. The main features of bone marrow blasts cells in Burkitt lymphoma/leukemia (BL) are L3 morphology, mature immunophenotype of blasts with surface IgM expression, and presence of typical MYC gene rearrangements.The aim of the study was to show discrepancy examples in laboratory signs of BL.Patients and methods. 10 patients (8 boys and 2 girls) aged 1 to 18 years were included in the present study. The inclusion criterion was the identification of discrepancies between flow cytometric, morphological and cytogenetic data.Results. In 2 cases there were no rearrangements of the MYC gene. In 2 patients, the L2 morphological variant went against the presence of typical MYC gene rearrangements. In one case, undifferentiated blasts cells were described by morphology together with presence of surface IgM, and atypical genetics. In 8 patients, there was no expression of surface IgM. Of these, patients with absence of cytomorphological data cytometric and genetic data were controversial.Сonclusion. The cases presented in this study and the cases described in the literature demonstrate the importance of an attentive and comprehensive approach in evaluating the results of laboratory tests in the diagnosis of BL.

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.

Introduction. Surface immunoglobulin expression is a main immunophenotypic criteria of mature subtype of B-lineage acute lymphoblastic leukemia. Although the majority of such cases represents Burkitt leukemia/lymphoma, it was shown for several times that membrane IgM could be detected in the absence of other mature lymphomas signs.The aim of the study was to evaluate heterogeneity of childhood acute lymphoblastic leukemia (ALL) with surface IgM expression and to assess correspondence of BIV EGIL ALL subtype with Burkitt lymphoma (BL) bone marrow dissemination.Materials and methods. Immunophenotypic, cytomorfologic and genetic data of 54 BIV-ALL cases were analyzed.Results. Among the studied patients 39 had BL, while others belonged to B-cell precursor ALL (BCP-ALL). All BL patients and none of BCP-ALL patients carried C-MYC rearrangement while in BCP-ALL group in 8 cases and in any BL cases KMT2A rearrangements were found. None of BCP-ALL children had L3 morphology according to FAB classification.Conclusions. B-lineage ALL with surface IgM expression is rather heterogeneous group of cases including typical BL and rare cases of BCP-ALL even with KMT2A-rearrangements. Combination of all available diagnostic technologies will allow precise split of these two different disease and select the appropriate treatment scheme.

Bone marrow tumor blasts immunophenotyping is an essential part of Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL) differential diagnostics. Nevertheless immunoglobulin heavy and light chains detection on the cell surface could meet several biological and methodological pitfals. Thus the aim of the present study was development of additional BL immunophenotypic criteria. Leukemic blasts antigen profile in 21 BL cases and 84 children with BCP-ALL was compared in a retrospective way. Antigen expression patterns in BL and BCP-ALL were significantly different. It was shown that even in cases with weak immunoglobulin M expression these two tumor types could be distinguished well by complex immunophenotype analysis. In present study all cases of CD34-negative B-lineage ALL without myeloid coexpression and with high CD20-positive cells proportion belonged to BL.

We developed and implemented in multicenter setting the standardized approach for flow cytometric minimal residual disease (MRD) monitoring in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Participation of multicenter group reference laboratories in several ring trial studies demonstrated high concordance rate between participants. Successful integration of one additional laboratory in the multicenter group has shown good level of our approach reproducibility. These results will allow implementing MRD detection in stratification system of pediatric ALL treatment protocols of Russia-Belarus multicenter group.

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.

Comparison of interpretation of acute lymphoblastic leukemia (ALL) flow cytometric diagnostics data was the aim of the study. Immunophenotyping data obtained from 10 patients with ALL were analysed separately in 26 laboratories from Russian Federation and Kazahstan. Results comparison showed four main type of discordance: B-lineage ALL diagnostics during heavy bone marrow regeneration, great variability of T-ALL interpretation, complexity of ambiguous lineage acute leukemia and, finally, very different report types, unique for each laboratory. All these problems are the serious obstacles for standardization of flow cytometric ALL diagnostics in multicenter setting. Continuation of similar QC rounds following by consecutive discussions with further development of consensus diagnostic algorithm could be the first step for standardization of ALL immunophenotyping in Russian Federation and CIS countries.

Hereby we present methodological aspects and prognostic significance of minimal residual disease (MRD) monitoring in infant acute leukemias. Based on our own experience we made algorithm for detection of MRD in this group of patients. We conclude that general concordance between MRD detection by flow cytometry and real-time polymerase chain reaction (PCR) for fusion gene transcripts achieved 87.0 %. Concordance was significantly lower during induction in comparison to consolidation/intensification and relapse treatment (78.6; 90.4 and 93.4 %, correspondingly; p = 0.002). It was not dependent on presence of normal B-cell precursors. Concordance between MRD results obtained by qualitative real-time PCR in bone marrow and peripheral blood samples was 84.5 %. Interestingly, all discrepant results (22 samples 15.5 %) were MRD-positive in bone marrow, but negative in peripheral blood. Despite high qualitative concordance rate between MRD detection in bone marrow and peripheral blood samples we could not show prognostic value of MRD monitoring in peripheral blood by fusion gene transcripts. Multivariate analysis revealed that MRD-positivity at time-point 4 in bone marrow was the only significant and independent prognostic factor of unfavorable outcome in the observed group of patients (hazard ratio 7.326; 95 % confidence interval 2.378–22.565).

In this review we present current state of cytogenetic and molecular genetic diagnostics of various aberrations in infant acute leukemias together with our own experience in this field. A complex characteristic of acute leukemias was performed for both MLL-positive and MLL-negative patients. Genetic heterogeneity was shown. Common and rare cytogenetic and molecular genetic aberrations were presented.

191 consecutive unselected children with acute lymphoblastic leukemia aged from 1 to 16 years were enrolled in the study. Bone marrow samples were obtained at the time of initial diagnostics as well as at days 15 (n = 188), 36 (n = 191), and 85 (n = 187) of remission induction. Minimal residual disease (MRD) was assessed by 6–10-color flow cytometry. Flow cytometry data at day 15 allowed distinguishing three patients groups with significantly different outcome (p ˂ 0.0001): 35.64 % patients with MRD < 0.1 % represented 5-year event-free survival (EFS) of 100 %; 48.40 % cases with 0.1 % ≤ MRD< 10 % had EFS 84.6 ± 4.2 %; 15.96 % patients with very high MRD (≥ 10 %) belonged to group with poor outcome (EFS 56.7 ± 9.0 %). At the end of remission induction (day 36) 36 children (18.85 %) with MRD higher than 0.1 % had significantly worse outcome compared to remaining ones (EFS 49.4 ± 9.0 and 93.5 ± 2.1 % respectively; p ˂ 0.0001). From a clinical standpoint it is relevant to evaluate both low-risk and high-risk criteria. Multivariate analysis showed that day 15 MRD data is better for low-risk patients definition while end-induction MRD is the strongest unfavorable prognostic factor.

Key words: chronic myeloid leukemia, BCR-ABL expression, automated GeneXpert method

Aim of the study – characterization of immunophenotype in infant acute myeloid leukemia (AML). 90 patients (40 boys and 50 girls) with acute leukemia (AL) aged up to 365 days were included in the current study. AML was found more frequently in infants than in older children (26.67 % and 10.83 % respectively; p = 0.0002). Significant immunophenotypic differences were observed in patients with and without MLL gene rearrangements. Number of cases in those tumor cells expressed CD99, CD61, CD133, CD15, NG2 varied between MLL-positive and MLL-negative groups. CD61-negativity, high CD99, CD15, CD133 and NG2 expression were immunophenotypic signatures of MLLrearranged infant AML, although CD99 and NG2 had the highest diagnostic efficacy. Thus infants’ AML immunophenotype differs significantly due to the presence of MLL gene rearrangements. Diagnostic immunophenotyping of infants’ AML allows predicting presence of MLL rearrangements by either CD99 or NG2 expression.

117 cases of infant acute lymphoblastic leukemia without Down syndrome (aged from 1 to 365 days) were included in the current study.Rearrangements of 11q23 (MLL) were revealed in 74 (63.2 %) patients. Among this group the most common rearrangement was t(4;11) q21;q23)/MLL-AF4 detected in 63.5 % cases, less frequently was found t(11;19)(q23;p13)/MLL-MLLT1 (in 18.9 % cases), t(10;11) p12;q23)/MLL-MLLT10 and t(1;11)(p32;q23)/ML L-EPS15 (each one in 6.8 %), t(9;11)(p22;q23)/MLL-MLLT3 in 2.7 %. Children under 6 months of age had significantly higher incidence of 11q23 (ML L) rearrangements in comparison with infants olde r than 6 months (84.0 % vs. 47.8 %, p < 0.001). P atients with translocations 11q23 (ML L) more frequently had BI-A LL and less frequently BII-ALL than children without these rearrangements (p < 0.001 f or both). Fusion gene transcript w as sequenced in 26 ML Lrearranged cases. Depending on breakpoint position within ML L and partner genes we detected 7 differ ent types of ML L-AF4 fusion gene transcript, 3 types of MLL-MLLT1, 2 types of MLL-EPS15. The most common fusion site within MLL gene was exon 11, detected in 14 (53.8 %) patients.

Aim of the study – immunophenotype description of infant acute lymphoblastic leukemia (ALL). 64 patients (29 boys and 35 girls) with acute leukemia (AL) aged from 0 to 11 months were included in the current study. ALL was found less frequently in infants than in older children (67.19 % and 87.69 %, respectively). BI-ALL was the most common immunological ALL type (60.46 %) in infant ALL, while BII-ALL was notably less frequent compared with other age groups (30.23 %). Significant immunophenotypic differences were observed in patients with and without MLL gene rearrangements. Number of cases in those tumor cells expressed CD10, CD20, CD45, CD133, CD15, NG2 varied between MLL-positive and MLL-negative groups. CD10- and CD20-negativity, high CD45, CD15, CD65 and NG2 expression were immunophenotypic signatures of MLL-rearranged infant ALL, although NG2 had the highest diagnostic efficacy. High CD34 and CD65 expression was frequently associated with presence of MLL-AF4 fusion gene. Thus infants’ B-cell precursor ALL immunophenotype differs significantly due to the presence of MLL gene rearrangements. Diagnostic immunophenotyping of infants’ ALL allows predicting presence of MLL rearrangements and NG2 is the most applicable single marker.

We performed clinical and laboratory characterization of patients with rare translocation t(1;11)(p32;q23) leading to MLL-EPS15 fusion gene formation. Study cohort consisted of 33 primary acute leukemia (AL) cases including 6 newly diagnosed and 27 patients previously described in literature. Among study group patients t(1;11)(p32;q23) was found most frequently in infant AL cases (median age 8 months). In acute lymphoblastic leukemia (ALL) male/female ratio was 1:3, in acute myeloid leukemia (AML) it was 1:1. Additional cytogenetic aberrations in 38 % of patients were revealed. The most frequent breakpoint position in EPS15 gene was intron 1. Four different types of MLLEPS15 fusion gene transcripts were detected. Primers-probe-plasmid combination for MLL-EPS15 fusion gene transcript monitoring by realtime quantitative polymerase chain reaction (RQ-PCR) was developed and successfully applied. In 3 patients RQ-PCR was done on genomic DNA for absolute quantification of MLL-EPS15 fusion gene. High qualitative concordance rate (92 %) was noted between minimal residual disease data obtained in cDNA and genomic DNA for MLL-EPS15 fusion detection.