ALBERT

Description: Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is characterized by low response rate to standard therapy and relapses in the course of treatment. CHOP-like therapy shows 70-80 % of overall response rate, though 2-year progression-free survival is observed only in 30-40 % of patients. Older patients are more frequently diagnosed with AITL than younger subjects. Usually the median age of those patients is 60 years. A search for new approaches to treatment of AITL has an important medical and social aspect. Aim: The aim of our study is to define rational approaches to treatment of younger patients with AITL, to assess the overall and progression-free survival depending on the type of therapy. Patients and methods: 45 patients with AITL were treated between 2002 and 2016 in our center. The diagnosis was verified according to WHO classification. We analyzed clinical outcomes in 17 (38%) patients younger than 55 years treated by different protocols. Results: Of 17 patients there were 9 men and 8 women with a median age of 41 (range, 29-55) years. 14 of 17 patients had Ann Arbor stage IV. Bone marrow involvement was detected in 7 of 17 cases by histological tests. Lung involvement was observed in 10 cases. B symptoms and elevated LDH level were present in all patients. Despite the younger age of the patients, 12 of 17 were classified as having an intermediate-high (n=5) and high (n=7) risk IPI score. There were 5 of 17 patients, who received CHOP-like therapy; other 12 patients were treated by longed therapy. There were 4 of 5 patients after CHOP-like therapy, who showed the progression from 1 to 4 (median 2) months, one achieved partial remission. There were 12 of 17 patients who were treated by the longed therapy according to RALL-2009 protocol (ClinicalTrials.gov public site; NCT01193933), successfully used for treatment of acute lymphoblastic leukemia in Russia. The program is based on non-intensive but uninterrupted treatment. After induction + consolidation phases (150 days) patients received maintenance therapy by interferon-A and thalidomide over 2 years. All 12 patients achieved complete remission, none of them showed disease progression. Two patients received autologous stem cell transplant (Auto-SCT) as first line consolidation treatment, conditioning regimen was CEAM (CCNU, etoposide, Ara-C, melphalan). One patient died after Auto-SCT from infection complications without disease progression. 11 (92%) of 12 patients treated by RALL-2009 protocol are alive, follow-up survival varies from 3 to 73 (median 19) months. A univariate analysis of overall and progression-free survival curves showed that longed therapy is more effective than CHOP-like therapy (Fig.1). Conclusion: Though, the study is small, the results show that higher efficiency of RALL-2009 protocol than CHOP-like therapy in younger patients withAITL. It is particularly important for working patients. The principle of non-intensive but uninterrupted usage cytostatic drugs and longed maintenance therapy by immunomodulators allows to avoid the early treatment failures and provides optimistic long-term results. Figure 1 (A) Overall and (B) progression-free survival of younger patients with AITL depending on the type of therapy. Figure 1. (A) Overall and (B) progression-free survival of younger patients with AITL depending on the type of therapy. Disclosures No relevant conflicts of interest to declare.

Description: Multipotent mesenchymal stromal cells (MSCs) have immunomodulatory properties and have been successfully used for treatment of autoimmune diseases and acute or chronic graft-versus-host disease. Therapy with MSCs is not always effective. It has been shown that MSCs immunomodulatory properties can be improved by means of various agents, such as IFN-g, TNF-a, IL-17. After 4 hours of IFN-g exposure the expression level of immunomodulatory genes increased - IDO1 300, CSF1 - 7, and IL6 - 2.4 times. MSCs typically express low levels of MHC class I, and no MHC class II or co-stimulatory molecules (e.g., B7-1, B7-2, or CD40), making them partially immunoprivileged. However, treatment with IFN-g leads to increased expression of HLA-DR antigens on MSCs. After injection to the patient the characteristics of MSCs differ from those which have been studied in culture due to their interactions with other cells in the bloodstream and tissues. In this study the model of MSCs and MSCs treated with IFN-g (IFN-g-MSC) interactions with allogeneic lymphocytes in vitro was developed. The aim of the study was to identify the changes in MSCs and IFN-g-MSCs characteristics after co-cultivation with lymphocytes in vitro in dynamics. Materials and methods MSCs were isolated from 13 bone marrow (BM) samples used for allogeneic hematopoietic cells transplantation and cultured by a standard method in aMEM with 10% fetal bovine serum (FBS). MSCs on 2-3-d passages were seeded 105 cells per flask with 25 cm2 bottom area and a day later 500 units/mL of IFN-g were added for 4 hours to half of the cultures. Then the media was changed on RPMI-1640 with 10% FBS. Some cultures were seeded with 106 allogeneic lymphocytes, to half of these cultures 5 mg/ml phytohemagglutinin (PHA) was added for lymphocytes activation. All flasks were cultured up to 4 days at 37°C and 5% CO2. After 1, 2, 3 and 4 days lymphocytes were washed from MSCs. MSCs were removed from the flasks with trypsin and the number of viable cells was determined by dye exclusion method (trypan blue). For each of the MSCs cultures the mean fluorescent signal intensity level (MFI) of HLA-DR was determined by direct immunofluorescent staining with anti-HLA-DR APC (BD Pharmingen) antibodies and measured on flow cytometer BD FACS Canto II (BD Biosciences, USA). Data are presented as mean ± standard error. Statistical analysis was performed using Student's t-test (considered reliable p

Description: Introduction Intensive “pediatric oriented” treatment with heavy cytostatic load, incorporation of allogeneic HSCT is now considered a backbone approach in adult ALL therapy. Highly myelosuppressive treatment is more toxic and less reproducible, so RALL has initiated non-intensive but non- interruptive protocol “ALL-2009”and started a prospective multicenter trial for adult Ph-negative ALL based on: 1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are 〉25% in bone marrow after 7 days of prephase; 2) de-intensified but non-interruptive treatment with doses modification according to the myelosuppression with total treatment duration of 127 weeks; 3) prolonged implication of L-asparaginase (total proposed dose 590.000 IU/m2); 4) autologous hematopoietic stem cell transplantation (HSCT) after non-myeloablative BEAM conditioning followed by prolonged maintenance – for T-cell ALL patients. Allo-BMT was an option for high risk patients with sibling donors. The study is registered on the ClinicalTrials.gov public site; NCT01193933. Methods and patients From Jan 2009, till June 2014, 30 centers enrolled 250 pts: median age 30 years (15-60 years), 115f/135 m; in 2,4% phenotype was unknown (n=6), B-lineage ALL - 63,2% (n=158), T-lineage ALL - 34% (n=85), biphenotypic - 0,4% (n=1). Cytogenetics was available in 62,4% of patients (n=156) and 41% of them (n=64) had normal karyotype (NK). 25,2% of patients (n=63) were in the standard risk (SR) group (WBC 100 for T-lineage; EGIL BI, T-I-II-IV; LDH 〉 2N; late CR; t(4;11)-positive), 39 patients were not qualified by risk group. The analysis was performed in June 2014. The median time of follow-up was 26,1 mo. Results Prednisolone was replaced with dexamethazone after prephase in 68,1% of patients (135 of 198). The portion of non-responders to PRD in SR and HR groups was 54% and 67%, respectively (p=0,06). CR rate in 228 available for analysis patients was 87% (n=198), induction death occurred in 10,5% (n=24), resistance was registered in 2,5% (n=6). The majority of CR patients (91%) achieved it after prephase (7,1%, n=16) and the 1st phase of induction (83,9%, n=164). Late responders constituted 9% (n=18). None of those factors (PRD sensitivity, initial risk group, immunophenotype, late response) influenced overall (OS) or disease-free survival (DFS). OS rate in older ALL patients (〉30) was substantially less than in younger ones (52,7% vs 73,6%, p=0,0009). DFS was comparable - 61,2% vs 71,5%, p=0,1. 24 of 75 (32%) CR T-ALL patients underwent autologous BMT after BEAM conditioning at a median time of 6 mo from CR and proceeded to further maintenance. No relapses were registered in this group so far. Allogeneic BMT was performed only in 14 patients (Ò-ALL-7, B-ALL-7) on the protocol. Totally 47 patients (20,6%) relapsed (16 with T-lineage, 31 with B-lineage ALL). At 48 mo OS for the whole group constituted - 65,6%, DFS - 69,3%. OS and DFS differed in B-ALL patients with NK in comparison with abnormal karyotype: 80% vs 57%,(p=0,01) and 81% vs 61%, respectively (p=0,02), but not in T-ALL patients. Conclusions Our data demonstrate that the proposed treatment approach is rather effective and reproducible. OS and DFS did not depend on various common risk factors (initial risk group, WBC, LDH, immunophenotype, late response, PRD resistance). The only independent risk factor for OS was age (〉30 y). In B-cell ALL abnormal karyotype became an independent adverse risk factor for OS, DFS, relapse incidence. Fig.1 Overall survival (A) according to age in the whole cohort and disease-free survival (B) in B-cell ALL according to karyotype Table 1 (A) OS in different age groups (B) DFS in B-cell ALL Figure Figure. (A) OS in different age groups Figure Figure. (B) DFS in B-cell ALL Disclosures No relevant conflicts of interest to declare.

Description: Introduction. Patients (pts) with oncopathology who have hyperexpression of c-MYC demonstrate low response to chemotherapy and poor prognosis. In our study we investigated the level of c-MYC gene expression in pts withmultiple myeloma (MM) and/or monoclonal gammopathy undetermined significance (MGUS) at the moment of MM/MGUS diagnosis. Patients and Methods. 40 patients with newly diagnosed MM/MGUS and 9 healthy bone marrow donors (as a control group) were included in our study. The median age of patients with MM/MGUS was 56 years (29-77), donors - 32 years (24-41). The bone marrow collection for examination was done at the moment of diagnosis. The investigated material was divided into 2 samples: all mononuclears and separated CD138+ cells. Level of c-MYC expression was identified by quantitative real time PCR (qRT-PCR). The whole number of qRT-PCR analysis was 98. Induction therapy (VCD/PAD) was initiated for 36 patients with MM, 4 patients with MGUS remained under observation. Antitumor response was evaluated after induction therapy according to the IMGG criteria. Results. From 98 samples among pts reliable results qRT-PCR and evaluated c-MYC expression were in 36 samples from total mononuclears and 17 from separated CD138+ cells. In all 18 samples from healthy donors: 9 from total mononuclear, and 9 from CD138+ cells results of qRT-PCR were reliable. Mean c-MYC expression level among MM/MGUS pts was 55.014 (2ΔCt) in CD138+ cells and in samples from total mononuclears - 17.585 (2ΔCt). In healthy donors the results were 7.183(2ΔCt) and 1.907 (2ΔCt) respectively. After induction therapy complete response (CR) was demonstrated 6 patients, very good partial response (VGPR) - in 7 patients, partial response (PR) - in 15 and other 5 pts were refractory. Mean c-MYC expression level in samples from separated CD138+ cells in pts with CR was-14.259 (2ΔCt), with VGPR-38.314 (2ΔCt), with PR-50.506 (2ΔCt), and in refractory pts-181.271 (2ΔCt), among patients with MGUS the level was 10.928 (2ΔCt). In samples from mononuclears: 5.138, 30.355, 11.877, 38.911, 7.323 (2ΔCt) respectively. Thus, response after induction therapy was worse among patients with high gene c-MYC expression (Figure 1 a). Such a correlation was not revealed in analysis of data from samples of total mononuclears (Figure 1 b). Conclusion. Mean c-MYC gene expression level in CD138+ cells among MM/MGUS pts was higher than among healthy donors (p

Description: Acute myelogenous leukemia (AML) is the most sensitive to natural killer (NK)-cell reactivity among blood malignancies treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Function of NK cells is regulated by their inhibitory and activating surface receptors, including killer-cell immunoglobulin-like receptors (KIRs). KIRs with specificity to different HLA class I-encoded ligands seem to play a major role in allorecognition: HLA-C allotypes with asparagine at position 80 (HLA-C1ligands) are recognized by KIR2DL2/3, HLA-C allotypes with lysine at position 80 (HLA-C2 ligands) are recognized by KIR2DL1and KIR2DS1, and HLA-B allotypes with a polymorphic sequence motif at position 77-83 (Bw4 ligands) are recognized by KIR3DL1.There are numerous but sometimes contradictory data about the role of KIR genes and genes of their HLA ligands in outcomes after HLA-identical related and HLA-matched unrelated HCST in patients with AML. The goal of our prospective study was to evaluate the influence of KIR genes and HLA class Iligands on overall survival (OS) and event-free survival (EFS) after allo-HSCT in adult patients with AML. 35 patients with AML (median age 36 years, range 19-60) treated with allogeneic HSCT in our transplant center from HLA-identical related (n=19) and HLA-matched (10/10) unrelated (n=16) donors were included in the study. Median follow-up was 18 months (range, 5-56). The pre-transplantation risk category included standard or high risk. Patients in complete remission 1 (CR1) were categorized as standard risk (n=22), whereas patients in 〉 CR1 were considered as high risk (n=13). In case of HLA-identical related HSCT donor KIR genotyping was performed simultaneously with HLA-typing. In case of HLA-matched unrelated HSCT donor KIR genotyping was performed in time of confirmatory HLA-testing or in day of HSCT. KIR genotyping was done using a PCR-SSP kit (Olerup, Sweden). Overall survival (OS) and event-free survival (EFS) were calculated by Kaplan-Meier method, and compared with log-rank test. OS was defined as survival without lethal event from any cause, EFS was defined as survival in complete remission without lethal event from any cause. The 3-year estimated OS and EFS in all patients were 66 and 43%, respectively. 10 patients died (29%), relapse (hematological and/or molecular) was diagnosed in 18 patients (51%). The pre-transplantation risk category was the main factor affecting OS and EFS after HSCT. The probability of the 3-year OS and EFS for standard-risk patients was 86 and 57%, respectively. Nobody of our patients with high risk lived more than18 months. Conditioning regimen, graft source and donor/patient gender combination had no significant effect on OS and EFS. The patients with unrelated HLA-matched donors had better (not significantly) EFS in comparison with recipients of related HLA-identical grafts (p=0.12). The influence of KIR and HLA- ligand genes on EFS after allo-HSCT was investigated in patients with standard risk. We did not find the immunogenetic factors (presence of B- haplotypes in donors, donor KIR B content, presence of centromeric or telomeric B- motifs in donors, presence of missing HLA ligand for any inhibitory KIR of donor), which significantly affected EFS, but we found two obvious tendencies. The patients with HLA-C1/C1 homozygosity had a tendency to improved EFS compared with patients having either HLA-C1/C2 or HLA-C2/C2 ligands (p=0.09). There was a tendency to better EFS in HLA-C1/x recipients of KIR2DS1 -positive allografts (p=0.09). Our data suggest that KIRs and their HLA class I ligands play role in the graft versus leukemia effect in AML. It seems that HLA-C1 homozygosity improves EFS in patients after allo-HSCT, and KIR2DS 1-positive donors are preferable for HLA-C1/x patients. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4840 The causes of drug resistance in acute leukemias (AL) have been studied very intensively and the key research was done on Bcl-2 family proteins. Last studies have showed that high level Bcl-2 expression in acute leukemia is really associated with drug resistance andpoor prognosis [Haematologica 2007, U. Testa]. It was demonstrated that lower Bax/Bcl-2 ratio (

Description: Introduction Allogenic bone marrow transplantation (allo-HSCT) with high-dose, post-transplantation cyclophosphamide (CY) nowadays has become an alternative for standard immunosuppression. Many groups have shown that high dose CY after allo-HSCT selectively deplete alloreactive T effector cells and downregulate Granzyme B expression in CD8+ T and NK cells after allogeneic HSCT. Despite that fact there is no data about other T cell populations, such as Tregs and their immunosuppression abilities after post-transplant CY. We studied Granzyme B expression in Treg on day +14 after allo-HSCT with post-transplant CY and standard immunosuppression. Patients and methods. Peripheral blood samples were collected in EDTA-tubes at day +14 after allo-HSCT in patients with hematological malignancies with post-BMT-CY alone (n=8) and patients with standard immunosuppression (post-HSCT CSA, MMF or MTX at standard dose) (n=18). The anti-CD4-PE-Cy7, anti-CD25-APC, anti-CD127-FITC and anti-Granzyme B-PE (Becton Dickinson, USA) antibodies were used to determine Treg cells population as CD4+ CD25high CD127low. We did not include anti-FoxP3 antibodies as FoxP3 is not so specific in humans and particularly after allo-HSCT due to technical difficulties, several isoforms and etc. CD4- lymphocytes (certainly containing CD8+ and NK-cells population that obligatorily express granzyme B) were used as internal positive control to define population of CD4+ CD25high CD127low GranzymeB+ cells and gMFI (geometric mean fluorescence intensity). 50000 of CD4+ cells were analyzed on a BD FACSCanto II (Becton Dickinson, USA). Results. Mann-Whitney U test was used to test for differences between Granzyme B+ Treg cells after post-transplant-CY alone and in a group of standard immunosuppression. The percent of CD4+ CD25high CD127low GranzymeB+ cells among CD4+ cells at day +14 after post-transplant CY alone was statistically higher (30.1±21,9; p=0.018*) than in patients with standard immunosuppression (3,52±1,56) (see Chart 1). There is no differences in Granzyme B expression (gMFI) in CD4+ CD25high CD127low cells after post-transplant-CY (2131,8±412,7) alone and in a group of standard immunosuppression (1718,17±316,8; p=0.541). It's worth to note that probably this mechanism in combination with depletion of alloreactive T effector cells and downregulation of Granzyme B expression in CD8+ T and NK cells help to prevent aGVHD in this group of patients. Conclusion We suggest that post-transplant CY spares Granzyme B expression in Tregs in a patients with post-transplant-CY and help to prevent aGVHD development in this group of patients. Despite the fact that the analyzed group is small, obtained data is important and needs further investigation. Figure 1. Granzyme B expression in Tregs after post-transplant-CY alone and in a group of standard immunosuppression. Figure 1. Granzyme B expression in Tregs after post-transplant-CY alone and in a group of standard immunosuppression. Disclosures No relevant conflicts of interest to declare.

Description: Introduction. Nowadays high-dose post-transplantation cyclophosphamide (CY) replace standard immunosuppression (IST). Thereby, the investigation of T-cells reconstitution after post-transplant-CY doesn't reach appropriate level, and probably it's very different from what we see after standard IST. We studied the reconstitution of memory T-cells on day of engraftment (WBC〉1000 cellsus) after allogenic hematopoietic stem cell transplantation (allo-HSCT) with post-transplant-CY and standard immunosuppression therapy. Patients and methods. During 2 years, 29 patients with different hematological malignancies were included in this study. Median of age was 36 years (24-60 years). 16 patients were males, 13 - females. 22 received RIC, 7 - myeloablative regime. Match unrelated donor (MUD) was in 17 cases, "Mismatch" MUD - 2, Match related donor (MRD) - 9, "Mismatch"MRD - 1. 4 patients were in relapse or disease progression. CY as alternative IST was administrated to 6 patients. Standard immunosuppression consisted of CSA, MMF or MTX at standard dose. Peripheral blood samples were collected in EDTA-tubes at day of engraftment after allo-HSCT (Me= 20 day (14-35)). Isolation of mononuclear cells from human peripheral blood was made by standard protocol using Lympholyte®-M Cell Separation Media (Cedarlane Labs). The anti-CD4- APC-Cy7 antibody (Becton Dickinson, USA) and FSC/SSC were used for determine population of CD4+T-cells. Anti-CD45R0- FITC (Becton Dickinson, USA) antibody were used to determine memory T-cells as subpopulation of CD4+ T-cells. Due to cyto- and lymphopenia 1,000,000 events was analyzed. Results. Mann-Whitney U test was used to test for differences between memory T-cells (CD4+ CD45R0+) after post-transplant-CY alone and in a group with standard IST. The percent of memory T-cells in CD4+ cell population at day of engraftment after post-transplant CY alone was statistically higher (74,3% ± 5,1% ,p=0.048*) than in patients with standard immunosuppression (49,4%±6,7%). Conclusion. We may conclude that patients with post-transplant CY had a different "T cell reconstitution profile". Reported data show us that probably post-transplant CY spares memory T-cells in contrast with standard IST, and also probably that CY is more selectively immunosuppressor than "gold standard" (such as CSA, MMF and etc.) not only on effector T-cells population. Despite the fact that the analyzed group is small, obtained data is important and needs further investigation. Disclosures No relevant conflicts of interest to declare.

Description: Background: The number of inhibitor hemophilia patients in Russia is presently about 200 patients (4% of all hemophilia patients). Current medical community is moving towards increasing the efficacy and safety of treatment, as well as the standardization of services and improvement of standards of care in rare diseases area. Patient registries and databases are key tools for the improvement of patient care, healthcare resources planning as well as social, economical and quality of life outcomes. Due to the lack of data on clinical course of disease, treatment approaches and outcomes, National Hematology Society initiated continuously running prospective, multi-center, open-label, non-interventional, observational Registry of INhibitor Hemophilia patients (RING) in July 2014. Aims: to document the natural history of hemophilia A or B disease in subjects with any type of inhibitors and to describe long-term treatment related outcomes in routine clinical practice. Methods: Data of all inhibitor patients are collected by physicians from patients medical records documenting the routine patient's examination and reflecting the medical practice at the particular treatment center. All data are entered into e-database using on-line access secured by the Operator. Results: In total 183 patients (101 adult and 82 children) from 47 centers were included in the Registry by June 2015. The majority of patients (90%) have severe hemophilia. The age of inhibitors diagnostics was: ≤10 years - 83%, 11-20 years - 3%, 21- 50 years - 5%, ≥51 years - 3% of patients. Chronic viral infections are diagnosed in 55 (30%) patients: 1 - HIV, 5- HBV and 49 - HCV. In 28% of patients annual bleeding rate (ABR) are ≥ 16, in 42% - 6-15, in 21% - ≤ 5. Approximately 25% of patients have zero joint ABR. Life threatening bleedings were registered in 25 patients (14%). Only 15 (8%) patients undergo immune tolerance induction (ITI); treatment with bypassing agents is administered in 151 (82%) patients. Due to the fact that activated prothrombin complex concentrate (aPCC) is not supplied by the State guarantees program 83% of patients receive rFVIIa (on-demand treatment - 50% and prophylaxis - 33%) and only 17% of patients have an access to aPCC treatment. The current data show that 34 (27%) patients with rFVIIa treatment need ≥3 injections to stop a bleeding episode thus they are identified as non-responders. Conclusion: The clear view of current treatment situation based on available Registry data demonstrates the necessity of administering alternative treatment approaches for non-responding to rFVIIa inhibitor patients, which would optimize resources of the State guarantees program. Disclosures No relevant conflicts of interest to declare.

Description: Introduction. For more than a decade it's postulated that the addition oftyrosine kinase inhibitors (TKI) to chemotherapy has dramatically improved the long term outcome in Ph-positive adult acute lymphoblastic leukemia (Ph+ ALL). Nevertheless whether do we need chemotherapy at all and if yes - how intensive it should be, is still the matter of debates. The only randomized trial addressing this issue (GRAAL, Blood 2015, 125: 3711-3719) has demonstrated the lack of benefit of more intensive induction at all checkpoints: complete remission (CR) rate, major molecular complete remission (MMolCR), molecular complete remission (MolCR), progression disease (PD) and resistance. We have conducted two consecutive trials in Ph+ ALL aiming to evaluate the efficacy of more and less intensive chemotherapy approach in combination with constant non-stop 600 mg Imatinib application. Aim. Toanalyze of the protocol RALL-2009 with ITK and RALL-Ph+-2012 effectiveness in patients with Ph+ ALL. The primary objective was the major molecular complete remission (MMolCR) rate after induction (70th day), patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. Patients and methods. Since Jan 2010 till July 2016, 120 new cases of ALL were verified in our National Research Center for Hematology with 68 (56,7%) of them being B-cell precursors ALL and 25 diagnosed as Ph-positive (36,8%). Since 2010 till 2012, 10 Ph+ ALL pts (median age 35 years (19-68), m/f (50%)/(50%), CNS disease=1, WBC〉 30*109/l=5(50%), bcr/abl transcript p190/p210/p190+210 6(60%)/3(30%)/1(10%)) were treated according to RALL-2009 protocol (ClinicalTrials.gov public site; NCT01193933) with parallel Imatinib. This protocol includes 8 cytostatic drugs and no intervals between treatment phases. Since 2012 till now 15 other pts (median age 40 years (17-61); m/f 7(46,7%)/8(53,3%); CNS disease=1, WBC〉30*109/l=5(33,3%), bcr/abl transcript p190/p210/p190+210 9(60%)/5(33%)/1(7%)) were included in RALL- Ph+-2012 protocol, based mainly on 600 mg Imatinib with prednisolone, VNCR, L-asp, followed by 6-MP and MTX. Both protocols suggested the shift to Dasatinib (100-140 mg) after non-achievement of MolCR at day 70 of treatment. MolCR was stated if no bcr/abl chimeric transcript was detected by PCR with 10-4 sensitivity. All patients were considered as candidates for allogeneic HSCT if HLA-identical donor was available. Results. At day 70th disregarding the chemotherapy intensity there was 40% of MolCR on both protocols (RALL-2009 - n=4 and RALL-2012 - n=6). No death within 2 months of induction/consolidation were registered on less intensive protocol in comparison with 2 cases on RALL-2009. Hematological CR was achieved in all pts (except two early deaths on RALL-2009) - 23 of 25 (92%). There was one autologous HSCT in older pts, included in RALL-2012 (n=3, aGVHD and severe infections, at a median +4 months after HSCT and more than 12 months of CR duration). The 3y OS, DFS and relapse probability (RP) for all 25 pts constituted 37,8%, 32,5% and 52,1% (Fig. 1). The long-term outcome on both protocols (RALL-2009 and RALL-2012) was similar: OS - 45% vs 27,7% (p=0,27), DFS - 45% vs 22,1% (p=0,94), RP - 35,7% vs 57% (p=0,29), respectively (Fig.2). Conclusion. De-intensification of the chemotherapy does not affect the effectiveness of the therapy Ph-positive acute lymphocytic leukemia in era of the tyrosine kinase inhibitors. We haven't seen differences in achievement of molecular remission when we deescalated chemotherapy (40% vs. 40%). However, when we reduced toxicity of the chemotherapy in ALL-2012 protocol, we were able to realize more extra allo-BMT and it could improve long-term results of the therapy Ph+ ALL. Figure Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL protocols. Figure. Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL protocols. Figure Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL-2009 and RALL-2012 protocols. Figure. Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL-2009 and RALL-2012 protocols. Disclosures No relevant conflicts of interest to declare.