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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.

Introduction It is postulated that the improvement in the overall treatment outcome in adult Ph-negative ALL came from the implementation of more aggressive pediatric-like protocols and higher portion of allogeneic HSCT. Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the opposite approaches: less intensive but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933. Patients and Methods The ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks prd/dexa with 3 instead of 4 dauno/vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks-continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications- with 1 day HD MTX and with 1 d HD ARA-C, both with L-asp and 3 ds dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11),L>100). No central MRD monitoring was performed. Since Apr 2009 till June 2015 20 centers had recruited 168 BCP-Ph-negative ALL pts with a median age 28 years (15-54), 84f/84 m. Full cytogenetics was available in 67,3% (n=113), 43,4% of them (n=49) had normal karyotype (NK), 10% (n=9%) had no mitosis, 47,6% (n=54) - different abnormalities (hypoploid-1, hyperploid-12, t(11q23)/MLL-8, del11q23-2, t(1;19)-2, t(12;21)-1;others-28). 26,7% of pts (n=45) were in the standard risk (SR) group (WBC 30; EGIL BI, LDH > 2N; late CR; t(4;11)-positive), 28 patients (n=16,8%) were not qualified by the risk. The analysis was performed in June 2015. 158 pts were available for analysis. Results CR rate in 158 available for analysis pts was 87,7% (n=139), induction death occurred in 9,1% (n=14), resistance was registered in 3,2% (n=5). The majority of CR pts (87,8%) achieved it after prephase (12,2%, n=17) and the 1st phase of induction (75,6%, n=105). Late responders constituted 12,2% (n=17). Allogeneic BMT was performed only in 9 of 144 patients who survived induction (6,2%). Totally 31 pts (22,3%) had relapsed. At 60 mo OS for the whole group constituted - 50%, DFS - 51.3%. In a univariate analysis among various risk factors (age <> 30y, initial risk group, WBC, LDH, immunophenotype, late response >35d, PRD resistance) age (>30 y) became statistically significant for OS, DFS and relapse probability (RP) (pic.1), abnormal karyotype - for DFS (30% vs 68%, p=0,04) and RP (42% vs 19%, p= 0,04). In a multivariate analysis no common risk factors were significant. Conclusions Our data demonstrate that the proposed treatment approach is rather effective. We believe that constant non-interruptive treatment without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that it should be very strict compliance of the pts to the protocol. All pts, mostly from the region hospitals who refused prolonged and constant treatment (~5%), relapsed. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: FL is one of the most frequent types of lymphomas: it consists about 22% of non-Hodgkin lymphomas in Russia. 20 % of pts have an aggressive tumor after standard therapy. In FL pts with unfavorable prognosis (FLIPI-1 III-IV, fast growth of tumor mass, B-symptoms, third cytological grade of tumor, bulky, absence of tumor response after first line R-CHOP-21 therapy) autoSCT allows to increase the overall (OS) and progression-free survival (PFS). Aim: To estimate an efficacy of HDT (high dose therapy) with following autoSCT in front-line therapy of FL pts with factors of poor prognosis. Patients and Methods: Since 2000 to 2015 years in National Research Center for Hematology were treated 39 FL pts with poor prognosis. All pts received R-CHOP-21 induction therapy. In 24 patients (62%) who hadn't partial response or poor prognosis patients with partial response after 4-6 courses autoSCT was performed. This group consists of 17 males and 7 females with median age 46 years old (31-68). Majority of pts (23/24) had IV stage of disease according to Ann Arbor. In 16/24 (66%) cases pts had bulky disease. 3/24 pts had phenomenon of leukaemization. Basing on FLIPI-1 criteria all pts were divided into 3 groups: low risk - 5/24, intermediate - 3/24, high - 16/24. B-symptoms were in majority of cases (18/24). 18/24 pts were diagnosed with I-II cytological grade of FL, 6/24 - III A/B. Basing on tumor growth pattern there was following ratio: nodular tumor growth revealed in 6/24 pts, nodular-diffuse tumor growth - in 15/24, diffuse tumor growth - in 3/24. Immunochemical analysis of serum and urine proteins was performed in 20/24 cases, among them increased level of serum β2-microglobulin was diagnosed in 10/20 pts. Increased activity of lactate dehydrogenase (LDH) was revealed in 16/24 pts. Bone marrow involvement at the time of disease onset was diagnosed in 18/24 pts. Results: After induction R-CHOP-21 chemotherapy pts underwent HDT which included two courses R-DHAP, following high-dose cyclophosphamide with rituximab, then high dose etoposide with rituximab. As condition regimen R-BEAM was performed. All 24 FL pts, who underwent autoSCT, continue to be in complete remission. Median follow-up was 31 months (7-178). Conclusions: Preliminary results of the first prospective study of intensive therapy of FL in Russia demonstrate that autoSCT in front line therapy provides to achieve a complete remission in pts with poor prognosis and allows to increase an overall and disease-free survival. Disclosures No relevant conflicts of interest to declare.

Background: Approximately 50% of diffuse large B-cell lymphomas (DLBCL) are defined as high-grade by IPI. They are characterized by aggressive course and poor response to standard chemotherapy (CT): 5-years overall survival (OS) rate of less than 30%. R-DA-EPOCH has demonstrated very optimistic results (overall and progression-free survival (PFS) were 90%), but high-risk patients (IPI 3-4) showed only 43% of OS and PFS [1]. The addition of high-dose AraC (12 g/m2) to the upfront therapy of high-risk DLBCL has significantly improved the outcome on Hyper-CVAD/HMA and mNHL-BFM-90 protocols [2, 3]. But high toxicity of these protocols restricts their application. We suggested that addition of courses R-HMA in rotation with R-DA-EPOCH could improve the treatment outcome and decrease toxicity. Aim: To evaluate the efficacy and toxicity of R-DA-EPOCH/R-HMA protocol in patients with untreated high-grade diffuse large B-cell lymphoma. Patients and Methods: 33 untreated DLBCL patients from 4 centers were enrolled in a prospective study between August 2013 - July 2015; stage II-IV; ECOG 0-3; median age 55 years (27-76); age ≥60y/ Results: The median follow-up is 12 months (4-24). There was no mortality associated with toxicity. The main non-hematological toxicities of R-HMA were infections (mucositis, pneumonia, sepsis, enteropathy) grades 1-2 and 3-4 in 90% and 10%, respectively. Hematological toxicity grade 4 for less than 4 days we observed only after courses R-HMA. Complete remission (CR) was achieved in 29 (88%) patients. In 2 patients we observed progression of the disease after first cycle of chemotherapy, in another 2 cases - partial remission after 2-3 cycles and following progression of disease. In patients older than 60 years with doses reduction in R-HMA failures were absent, except one later relapse after 13 month CR. With a median follow 12 months overall and disease-free survival of 33 patients constituted 90,5% and 74% , respectively. In a group of patients older than 60 years results of therapy seemed to be better than in young patients: OS were 100% vs 85,6% (p=0,1), DFS were 80% vs 74,9% (p=0,2), respectively. So the combination of R-DA-EPOCH/R-HMA may be considered as optimal intensive approach in the older patients. Conclusions: TheR-DA-EPOCH/R-HMA protocol demonstrated acceptable toxicity and high efficacy in patients with high-grade DLBCL. This protocol has shown optimistic results in the elderly patients and it could be recommended for further investigation in that group. Ññûëêè: 1. Salit RB, Fowler DH, Wilson WH, et al. Dose-adjusted EPOCH-rituximab combined with fludarabine provides an effective bridge to reduced-intensity allogeneic hematopoietic stem-cell transplantation in patients with lymphoid malignancies.J Clin Oncol. 2012. 10;30(8):830-6. 2. Oki Y, Westin JR, Vega F, et al. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol 2013; 163(5):611-20. 3. Magomedova AU, Kravchenko SK, Kremenetskaia AM, et al. Nine-year experience in the treatment of patients with diffuse large B-cell lymphosarcoma. Ter Arkh. 2011;83(7):5-10. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

Introduction. Favorable therapeutic regimen for pregnant women with primary mediastinal B-cell Lymphoma (PMBCL) is determined by tumor mass, somatic status, period of pregnancy and potential risk of teratogenic effects of medications which penetrate through placenta. Aim. To estimate chemotherapy efficacy of PMBCL in case of pregnancy and its toxicity for fetus. Patients and Methods. Since 2004 to 2015 years in National Research Center for Hematology were treated 106 patients with primary mediastinal B-cell lymphoma. In 8 (7,5%) from them disease debuted during 2-3 trimester of pregnancy, one women had two fetuses simultaneously. Before delivery women underwent induction chemotherapy with VACOPB- regimen in 5/8 cases and with R+DAEPOCH in 3/8 cases. Results. After induction treatment had been performed 6/8 women achieved a partial remission, 1/8 had progression, 1/8 - complete remission. High dose chemotherapy was performed in 7/8 women after 1 month following delivery. It was born 9 children (4 boys and 5 girls). Median body weight was 2000 g. (1300 - 3600 g.). Median growth was 47 cm. (40 - 53 cm). In two cases when rituximab had been administered to women before delivery, children were diagnosed with intrauterine pneumonia. One child, born from woman after VACOPB chemotherapy had thrombosis of superior vena cava. All women continue to be in complete remission of PMBCL, children are practically healthy without malformations. The median follow-up of patients was 40 months (15 - 78 months). Conclusions. Pregnancy is not a contradiction for induction chemotherapy of PMBCL in 2-3 trimesters. Rituximab shouldn't be administered before delivery because of a high risk of infectious in fetus. Disclosures No relevant conflicts of interest to declare.

Background: Course of multiple myeloma (MM) is associated with hemostatic disorders that can lead to bleeding or thrombosis. According to previous studies the most risky period of time for thrombotic complication is the first year after diagnosis. Aims: The study was aimed to analyze of hemostasis conditions in newly diagnosed (ND) MM patients (pts) and to compare their initial status with the status after induction therapy (IT) and with the status of healthy volunteers (HV). Patients and Methods: 17 pts with ND MM: 10 males, 7 females at the age of 26-72 (median age - 54) were involved in the study. The distribution of the stages among the participants according to Durie-Salmon system: stage I - 1 pts, stage II - 5 pts, stage III - 8 pts, stage III in 8 pts. Immunochemistry variants: IgG - 11 pts, IgA - 2 pts, MM B-J - 4 pts. Average paraprotein (PP) level was 34g/L (0,8 - 78). HV group consisted of 26 persons without serious diseases, 40 - 70 y.o., (median age 50). Hemostasis analysis was taken place twice: before and after the IT which included 4-8 bortesomib-containing cycles (PAD, VCD, VD). After the IT 6 pts achieved CR, 5 pts - VGPR, 4 pts - PR and 1pt was resistant. Average value of PP decreased to 8 (0,1 - 29,7). Routine tests: activated partial thromboplastin time (APTT, normal rate 25-38 sec), international normalized ratio (INR, normal rate 0.85-1.15), D-dimer concentration (normal rate 0-500 mkg/l). Two global tests: thrombin generation test by using endogenous thrombin potential (ETP, normal rate 760-1450 nM*min) and thrombodinamics (TD), characterized by the initial clot growth velocity (Vi, normal rate 36-56 um/min), stationary velocity (Vst, normal rate 20-30um/min), and density of a fibrin clot measured by light scattering from clot (D, normal rate 16000 - 32000 conventional units). Hypocoagulability wasassessedby data APTT > 38 sec, INR> 1.15, ETP < 760 nM*min, Vi < 36 um/min, Vst < 20 um/min, D < 16000 cu. Hypercoagulability was considered in cases when APTT < 25 sec, INR < 0,85, D-dimer > 500 ng/ml, ETP > 1450 nM*min, Vi > 56 um/min, Vst > 30 um/min, D > 32000 cu. Statistics. Ðaired t-test and Pearson correlation coefficient (r) have been got with SAS 9.1. 95- percent CI has been used. Results: ND MM APTT evaluation demonstrated normal coagulation in 13pts and extended one in 4pts (48 sec [38-57]). INR was normal in 13 and increased in 4 cases (1.3% [1.2-1.5]). Increased concentration of D-dimer was revealed in 7pts (3810 ng/ml [350-7270]). ETP was normal in 12 and increased in 5 cases (1592 nM*min [1406-1779]). Vi was normal in 11 and increased in 6pts (62 um/min [58-65])). Vst was reduced in 1pts (15um/min), normal in 10pts and increased in 6pts (36um/min [28-44]). Density of clot was normal in 8 pts and decreased in 9pts (9769 UE [6379-13160]). (Tab. 1) After IT only 1 pt had elongated APTT (44sec), the results of the others were normal. INR was normal in all cases. D-dimer concentration was normal in 12pts and increased in 5pts, but this data was statistically less (1080ng/ml [500-1003]) than in ND MM. ETP was normal in 13pts, elevated in 4 pts (1604 nM*min [1099-2109]). Vi was normal in 12pts and increased in 4pts (61 um/min [57-65]). Vst was decreased in 2pts (13 and 14um/min), normal in 13pts and increased in 2 (32 and 43um/min). Density of clot became normal in 14pts, but clot remained not dense enough in 3 pts (9512 [13606-15779]). (Tab. 1) We found that inverse linear relationship between PP level and blood clot density was more significant in ND MM (Fig. 1, fig.2). Statistically significant difference was revealed between clot density in ND MM and pts in PR or CR and between them and HV (Fig. 3). Furthermore, a significant difference was identified between D-dimer concentration in ND MM pts and after IT (Fig. 4). Conclusions: MM pts have complex disorders of hemostasis characterized by a tendency to hyper- and hypocoagulation at the same time. In spite of an increased tendency to thrombosis confirmed by D-dimer, ETP, TD, pts are under risk of bleeding related to the formation of defective clot and elongated APTT. According to the obtained results one can assume that PP embedded in the clot and disorder its structure. However, further studies are needed to confirmthat assertion. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

Introduction The majority of clinical recommendations on MDS indicate the use of IST for low-risk hypoplastic MDS patients. ATG followed by cyclosporine A (CSA) is recommended for younger pts with normal karyotype or with +8, CSA - for older patients with autoimmune phenomenon or hypoplastic bone marrow. There are no reports on the use of CSA with splenectomy as a combined IST for MDS patients. Here we report the long term (20 years) results of the single center trial comprising 61 MDS pts treated with CSA as the first or the second line treatment + splenectomy. Patients and methods. Since 1995 till June 2015, 61 patients were included in the combined IST protocol. There were 34 males, 27 females; median age constituted 39 years (16-74), refractory cytopenias with multileaneage dysplasia = 46, RAEB1/2 = 15; IPSS - low-risk= 4, intermediate 1 =40, intermediate-2 =9, high =4; no risk evaluation - 4 patients. All patients had trepanobiopsy evaluation, half of them - bilateral. It worth to note that bilateral trepanobiopsy permitted to redefine cellularity in 15% of patients. Pure hypoplastic forms of MDS were registered in 38 patients (63%), combination of hypoplasia with hyperplasia or normal cellularity - in 10 (16%), hyperplastic forms - in 13 (21%); non-clonal lymphoid nodules in b/m were detected in 29 pts (46%); fibrosis - in 7. Cytogenetics was done in 57 pts, 32 had normal karyotype; 5 had trisomy 8; 8 - high risk cytogenetics (-7/7q-, complex); 8 - different intermediate. Cyclosporine A was applied at a dose 5 mg/kg per day, followed by reevaluation of response at 2-3 months. In case of response CSA was continued, if there was no response or it was inadequate - splenectomy was done followed again by CSA; if progression occurred - CSA was stopped. We consider splenectomy as a component of the programmed IST as it leads to removement of a big lymphoid organ. For younger patients ATG for 20 mg/kg for 5 days could become the 2nd or the 3rd line of treatment. For patients with sibling donors allogeneic HSCT was an option. Analysis was carried out in June 2015. The patients were grouped for analysis according to cellularity (hypo vs hyper, in case of combination hypo with hyper/normal the case was considered as hypocellular), % of b/m blast cells (<> 5%), IPSS index (low/int-1 vs int-2/high), cytogenetics, the presence of lymphoid nodules. Results. CSA was started as the 1st line treatment in 42 patients, as the second line (after ATG or splenectomy or ESA) - in 20. 5 patients were transplanted from sibling donors. 35 patients received CSA as monotherapy (16 of them had a progression or a transformation to AML). Totally splenectomy was performed in 20 patients, in 8 patients it was followed by additional immunosuppression with ATG (9 patients) or MMF (1 patient). Splenectomy was performed by laparoscopy, no deaths or sever complications were noted. Half of the splenectomized patients achieved sustained response after operation and continuation of CSA. On the whole 18 patients had progression to RAEB or transformation to AML (1 from low-risk group, 7 - int1, 6 - int2, 5 - from high risk). Complete remission was achieved in 15 patients (24%), with overall response rate of 56% (n=34) with a median duration of response - 21 months (1-230 mo). The 20-years survival data revealed highly statistical difference between hypoplastic forms of MDS vs hyperplastic (38% vs 0%), bone marrow blast cells less vs more than 5% (43% vs 5%), IPSS categories low/int1 vs int2/high (50% vs 0%), cytogenetics favorable vs intermediate vs high (62% vs 35% vs 0%) (Pic.1). No differences were detected in patients with or without lymphoid nodules in b/m (38% vs 35%). Conclusions Our small but prolonged study has demonstrated a substantial long-term efficacy of the combined IST. CSA followed by splenectomy is a reasonable treatment approach in MDS patients with hypoplastic features in bone marrow, normal or intermediate karyotype, low blast cell count, low/int1 IPSS score. Pic.1 Overall survival of MDS patients treated with combined IST depending on cellularity, blast cells count, cytogenetic features and IPSS score. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Aim. To evaluate late nephrotoxicity of intensive modified program NHL-BFM-90 (mNHL-BFM-90) in adult poor-prognosis patients with diffuse large B-cell lymphoma (DLBCL). Materials and methods. The data of laboratory tests of blood and urine of 40 patients with DLBCL which received mNHL-BFM-90 protocol in the Hematology Research Center in the period from 2002 to 2009 years was analyzed. Group consisted of 20 men, 20 women, aged from 31 to 76 years, median age - 56.5 years at the time of the survey, the median period after therapy- 6 years. Individual cumulative dose of ifosfamide - 8-12 g / m 2 , cyclophosphamide - 2-3 g / m 2 , methotrexate - 6-9 g / m 2 . Comparison group included 19 patients (8 men and 11 women), aged from 39 to 78 years, median age - 70 years at the time of the survey, who received therapy to CHOP or R-CHOP. The median period after therapy - 5,5 years. Individual cumulative dose of cyclophosphamide - 3-6 g / m 2 . Laboratory tests of blood and urine were performed before chemotherapy and after 5 years after treatment. Results. From all 40 patients with DLBCL received mNHL-BFM-90, signs of chronic kidney disease were found in 32 (80%) patients, only 2 (5%) of them showed a decrease in creatinine clearance daily. In comparison group signs of chronic kidney disease were found in 12 (63%) patients, 2 patients (10.5%) showed a reduction in the daily creatinine clearance. No significant differences in the manifestations of nephrotoxicity in the long term between comparison groups were found. No significant differences in the manifestations of nephrotoxicity in the long term period were found between two groups of patients (who underwent and not underwent acute renal failure during high-dose chemotherapy). Amount of nephrotoxicity signs was significantly dependent on the presence of hypertensive disease in history (p = 0.02). Conclusion. Nephrotoxicity of high-dose mNHL-BFM 90 exceeds significantly nephrotoxicity program CHOP / R-CHOP. Conducting high-dose chemotherapy in 10 (25%) patients complicated by acute renal failure, 2 (20%) patients required hemodialysis in contrast to the group of standard chemotherapy without such complications (p=0,01). However, in the long term observations there weren9t significant differences in the nephrotoxic manifestations between two groups. Impaired renal function in the long term period observed in 100% of patients undergoing acute renal failure during treatment and only in 71% of patients without acute renal failure (p=0,04). It was comparable repairing of renal function in the long term in patients undergoing high-dose therapy between patients with and without acute renal failure among those who showed signs of chronic kidney disease. Disclosures No relevant conflicts of interest to declare.

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is a rare tumor derived from follicular T-helper and characterized by low response rate and relapsing course to standard therapy. CHOP-like therapy shows 70-80 % of overall response rate, though 2-year progression-free survival is observed only in 30-40 % of patients. Unsatisfactory results of treatment angioimmunoblastic T-cell lymphoma by ÑÍÎÐ-like therapy require searching new approaches to therapy. Aim: To define a rational approach to treatment of angioimmunoblastic T-cell lymphoma. Patients and methods: Ñlinical outcomes of 23 patients with newly diagnosed AITL treated between June 2002 and July 2015 we retrospectively analyzed. The diagnosis was verified according to WHO classification. Results: Among the 23 patients 14 men and 9 women were included with a median age of 63 (range, 29-81). Twenty-two of 23 patients had Ann Arbor stage IV. Bone marrow involvement was detected in 21 of 23 cases by histological investigation. Nine of 23 patients received CHOP-like therapy; other 14 patients were treated prolonged therapy. Eight (89%) of 9 patients after CHOP-like therapy had treatment failure. Time to disease progression ranged from 1 to 7 months (median 3). Fourteen of 23 patients were treated by prolonged therapy consisting of low dose cytotoxic drugs weekly and supporting the therapy by interferon-A and thalidomide. Supporting therapy has administrated after achieving complete remission and was continued in 2 years. Prolonged therapy wasn't finished in 3 patients with severe infections and somatic pathology. Eleven (79%) of 14 patients treated by prolonged therapy achieved complete remission, treatment was finished only in 5 of 11 patients; follow-up varies from 3 to 67 months, a median 29. Univariate analysis of progression-free survival curves showed that prolonged therapy is more effective than CHOP-like therapy (p < 0.01) (Fig.1). Prolonged therapy was performed in 4 of 8 patients with progression disease after CHOP-like therapy; 2 patients achieved a complete remission, continuing 41 and 77 months. Conclusion: Although, this was a small retrospective study, the results show that efficiency of prolonged therapy is better than CHOP-like therapy in patients withangioimmunoblastic T-cell lymphoma. Prolonged therapy allows preventing early treatment failures. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction. Primary mediastinal B-cell lymphoma (PMBCL) amounts from 0,9 to 4% of Non-Hodgkin Lymphomas. Predominantly suffer young women. All relapses in PMBCL occur as early events. Taking into account unfavorable prognosis in case of relapse or progression of PMBCL (2-year overall survival (OS) is about 15% [Kurvilla J., 2008]), it's necessary to achieve a complete remission (CR) in first line treatment. Aim. To compare an efficacy of R-DA-EPOCH followed by R-DHAP and autologous peripheral blood stem cell transplantation (autoSCT) with BEAM conditioning regimen with modified (m) NHL-BFM-90 chemotherapy protocol in pts with partial remission (PR) of PMBCL. Patients and Methods. In 107 pts (34 males, 73 females) diagnosis of PMBCL was established according to WHO criteria. All pts had stage II of disease according to Ann Arbor classification. 30 pts received R-DA-EPOCH, 77 pts - m-NHL-BFM-90 ± R. Median age of pts in R-DA-EPOCH group was 28 years old (from 20 to 67 years old); in m-NHL-BFM-90 ± R-group - 77 years old. Increased LDH concentration was revealed in 24 from 30 (80%) pts in R-DA-EPOCH group and in 75/77 (97%) pts from m-NHL-BFM-90 ± R group. Bulky mediastinal disease was in 30/30 (100%) pts in R-DA-EPOCH group and in 59/77 (76%) - m-NHL-BFM-90 ± R group. In case of CR after 6 courses according to computer tomography and PET scanning treatment was completed. In case of PR pts underwent 2 R-DHAP courses with autoSCT (BEAM conditioning regimen). All pts from m-NHL-BFM-90 ± R group independently from PET-results stopped treatment. All cases of treatment failure occurred till one year of observation. Kaplan-Meier method was used to calculate OS and relapse-free survival (RFS). OS was defined as time from diagnosis to death from any reason; RFS was defined as time from diagnosis until relapse or death from any cause. Results: After 6 R-DA-EPOCH therapy CR was achieved in 24/30 (80%) pts, 6/30 (20%) pts had PR and underwent 2 R-DHAP courses followed by auto-SCT (BEAM). 2- RFS and OS was 100%. Median follow up was 16 months. In m-NHL-BFM-90 ± R group 10-year RFS and OS were 85% and 92%, respectively. Median follow up was 53 months. Conclusion: High dose pulsed m-NHL-BFM-90-chemotherapy as well as R-DA-EPOCH allows getting high efficacy of primary mediastinal B-cell lymphoma therapy. Although future analysis will show more distant results of R-DA-EPOCH chemotherapy. Disclosures No relevant conflicts of interest to declare.

Background. Patients with myeloproliferative neoplasms (MPN) have a high risk of portal thrombosis. This problem leads to the disability of the patient without prompt treatment, or with resistance to conducted therapy. The aim of this publication is to present own experience with antithrombin III, which subsequently will form the basis for the development of new treatment approaches for acute and subacute portal thrombosis resistant to therapy with anticoagulants (heparin, low molecular weight heparins (LMWH)) in patients with MPN. Material and methods. At the outpatient department of National Hematology Research Center (Moscow) were observed 5 patients with MPN (3 patients with primary mielofibrosis, 2 essential thrombocythemia). Course of the disease was complicated by acute and subacute thrombosis of the portal system, resistant to treatment by anticoagulants. Antithrombin III was used for treatment of these patients in the outpatient department first time. Antithrombin III was administered regardless of the level of endogenous antithrombin III in combination with LMWH in therapeutic or prophylactic doses. The drug was used at a dose of 1,000 IU by intravenous bolus injections of 3-5 in 3 days (total dose rate of 3000-5000 IU). Results. Treatment was performed on an outpatient basis, the side effects were not observed. In all 5 cases, use of the antithrombin III in combination with LMWH observed positive clinical effect as a quick relief of pain, and early recanalization of the thrombosed vessels (from 3 weeks to 1.5-2 months) (Table 1). In all cases it was normalization of increase of endogenous antithrombin to normal values​​; it was observed positive changes in other parameters: the value of D-dimers, fibrinogene, XII-dependent fibrinolysis ([Figure 1][1]). Conclusion. Antithrombin III therapy is indicated for the management of acute and subacute portal thrombosis in patients with MPN who are resistant to treatment with anticoagulants (heparin and LMWH). The advantage of the therapy is the possibility of therapy on an outpatient basis without the risk of side, including hemorrhagic complications. | Patient | Diagnosis. Clinical features. | Localisation of thrombosis | Preliminary treatment. Duration of the preliminary treatment | Treatment with antithrombin III, 1000 IU. | | -------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------- | ----------------------------------------------------------------------------------------------------- | ----------------------------------------- | ---------------- | | Number of injections | Total dosage | The efficiency. Duration of treatment | | 1. L.T | PMF, JAK-2 - 31%. Thrombocytosis, leukocytosis. | The portal and superior mesenteric vein (complete occlusion). | Heparin, clopidogrel, aspirin. 2 weeks. | 3 | 3000 IU | Pain relief after the first injection. Complete recanalization of the portal and superior mesenteric veins in 3 weeks | | 2. D.T. | PMF, JAK-2 - 83%. Ðistory of bleeding from the duodenal ulcer. | Occlusive thrombosis of the portal and splenic veins. | The patient received long-term antiplatelet therapy. | 5 | 5000 IU | Partial recanalization of the portal vein, complete recanalization of the splenic vein in 8 days. Complete recanalization of the portal vein in 4 weeks. | | 3.V.T. | ET, Varicose veins of the esophagus and stomach grade 2-3. History of gastric bleeding. Splenectomy with secondary thrombocytosis. | Occlusive thrombosis of the main part and the left branch of the portal vein. | Heparin, LMWH, aspirin, clopidogrel. 1.5 months. | 5 | 5000 IU | Recanalization of the left branch of the portal vein in 10 days, partial recanalization of the portal vein in 1.5 months. | | 4.Ts.I. | PMF, JAK-2 - 25%. History of radiation therapy of the spleen. | Thrombosis of the main part and the left branch of the portal vein, splenic vein. | Heparin, LMWH - 5 months with partial recanalization of the portal vein, the persistent pain. | 5 | 50000 IU | Pain was stopped in 2 weeks, recanalization of the left branch of the portal vein, the appearance of the blood flow in the hepatic portal vein in1 month. | | 5. I.R. | ET, JAK-2 – 34%. Genetic thrombophilia - prothrombin gene mutation G20210A (het). Pregnancy 22-23 weeks | Hepatic vein thrombosis (Budd-Chiari syndrom). Ascites, hepatomegaly, splenomegaly. | Heparin LMWH - 2 months with reduction of ascites, no changes of thrombosis. | 3 | 3000 IU | Absence of pain and ascites, partial recanalization veins of the liver, a significant decrease liver and spleen size, a significant improvement in coagulation in 2 months. | Abstract 5098. Table 1. Dynamics of clinical parameters in therapy with Antithrombin III. ![Figure 1.][2] Figure 1. Disclosures No relevant conflicts of interest to declare. [1]: #F1 [2]: pending:yes

Background: Patients (pts) with multiple myeloma (MM) have an increased risk of thrombosis. Previous studies have shown that 3.7–4.6% of pts undergoing peripheral blood stem cell (PBSC) mobilization developed thrombotic complications. Aims: The aim of the study was to investigate the blood coagulation status in MM pts during PBSC mobilization. Methods: 20 pts: 12 males, 8 females at the age of 27 – 64 years (median 53) were included in the study. After bortezomib-containig induction therapy 5 of them achieved CR, 11 – VGPR and 6 – PR. PBSC mobilization was performed by using cyclophosphamide (CY, 4g/m2) and granulocyte colony-stimulating factor (G-CSF, 5mcg/kg/day). A central venous catheter (CVC) was placed on the day before CY administration and heparin-sulphate continuous infusion (500 IU/hour) as thromboprophylaxis was started. Subcutaneous injections of G-CSF were administrated when WBS decreased less 1 x 109/l. The procedures of stem cell collection were carried out when the number PB CD 34+ cells exceeded 10 x 103/ml. Hemostasis analysis was performed 5 times, namely before (point 0) and 24 hours after heparin administration (point 1), the next day after CY infusion (point 2), before G-CSF administration (point 3) and on the day of PBSC collection (point 4). Condition of hemostasis was assessed by the results of activated partial thromboplasin time (APTT, normal rate: 25 – 38 sec) and thrombin generation test, namely by using endogenous thrombin potential (ETP, normal rate: 760 – 1450 nM*min) in every point. Hypercoagulation was considered in cases when APTT < 25 sec and ETP > 1450 nM*min. And hypocoagulation was estimated by data APTT > 38 sec and ETP < 760 nM*min. Time series analysis performed using TIMESERIES procedure in SAS 9.3 (SAS Institute Inc. Cary, NC). Significance level of alpha was set at 0.05. Results: Before heparin administration (point 0) APTT evaluation showed normal coagulation in 18 pts (90%) and hypocoagulation in 2 pts (mean 34 sec, 95% CI 32 – 36 sec) (Figure 1). ETP was normal in 14 pts and increased in 6 cases (mean 1441 nM*min, 95% CI 1304 – 1578 nM*min) (Figure 2). Pts in CR demonstrated no significant difference in coagulation status compared to pts in VGPR or PR. On the next day after CVC incorporation and starting thromboprophylaxis (point 1), APTT and ETP have significantly changed (p < 0,05) to hypocoagulability in response to heparin infusion: mean data APTT became 38 sec (95% CI 36 – 41 sec) and mean ETP - 938 nM*min (95% CI 801 – 1074 nM*min). On the next day after CY administration (point 2) APTT was statistically significantly decreased (p < 0.05) reaching 35 sec (95% CI 34 – 36 sec). ETP had also changed but to a lesser degree, the mean was 1079 nM*min (95% CI 929 – 1229 nM*min). Hemostasis at point 3 was characterized by APTT mean 38 sec (95% CI 37 – 40 sec) and ETP mean 1057 nM*min (95% CI 911 – 1203 nM * min). On the day of PBSC collection mean values of measured parameters have not changed as compared to the previous point: APTT was 40 sec (95% CI 37 – 43 sec) and ETP was 1046 nM*min (95% CI 916 – 1176 nM*min) (Table 1). Thrombotic events were diagnosed in 2 cases of the total of 20 pts. There were two females, 54 and 56 years, both in CR MM. The first pt developed CVC-associated thrombosis. She had additional risk factors such as obesity (BMI – 44) and heterozygous MTHFR polymorphism. The second pt demonstrated acute violation of cerebral circulation which arose due to occlusion of the right internal carotid artery. She was a hard smoker and heterozygous FV Leiden polymorphism. Having confirmed thrombotic complications, the dose of heparin had been increased. Besides, folic acid was administrated for the first pt and combination of aspirin and pentoxifilline for the second. PBSC collection was successful for both pts. Summary: The results of our study identify latent hypercoagulation status in 30% pts of confirmed by elevated ETP. Those changes were registered despite of achievement CR or PR MM. Thrombotic complications have developed in 10% from our group. Notably, one should consider individual risk factors for each pt. Figure 1 Figure 1. Figure 2 Figure 2. Table 1. Measurements data of parameters of hemostasis Measuring point Mean APTT (95% CI) Mean ETP (95% CI) 0 33.6 (31.2-35.9)* 1441.1 (1304.3-1577.9)* 1 38.6 (35.7-41.6)* 937.6 (801.3-1074.0)* 2 35.2 (33.9-36.5)* 1079.0 (928.8-1229.2)* 3 38.1 (36.7-39.5) 1057.2 (911.4-1203.1) 4 39.6 (36.5-42.8) 1046.2 (916.0-1176.3) * Means in the same column are significantly different (P Disclosures No relevant conflicts of interest to declare.

Introduction Proposed in 1916 by Shlofferom Katznelson, splenectomy has been widely used since then in the treatment of immune thrombocytopenic purpura. ITP seems to be the most common indication for SE. According to the available literature up to 50-80% of laparoscopic SEs are being performed in patients with ITP, in our Centre - up to 20%. Laparoscopic SE should be considered as the treatment of choice for recurrent thrombocytopenic purpura after the initial response to steroid therapy. Indications for SE include all forms of immune thrombocytopenic purpura, requiring repeated courses of hormone therapy, as well as the cases of developed life-threatening complications, as for example intracranial hemorrhage. Earlier indications for splenectomy included lack of the hormone replacement therapy effect for 6 months. The dimensions of the spleen in patients with ITP are usually within normal or slightly increased limits. Thus these patients may get all the benefits of minimally invasive surgery. Goal: 1. to assess the results of the SE in the treatment of ITP 2. to clarify its place in the treatment of ITP. 3. to investigate the influence of the multiple lines drug therapy on the efficiency of SE in patients with ITP. Materials and Methods 87 SE have been performed in patients with ITP in 2008 – 2013, among them 63 female, 24 male. Median age 28 years old. Duration of the disease before surgery was from one month to 51 years, in 69 patients - over 6 months. 62 patients (71.3%) before SE received only corticosteroids. 25 (28.7%) received besides corticosteroids: 14 - GCS + immunoglobulin 5 - GCS + rituximab 7 - GCS + romiplostim 3 - GCS + cyclosporine 1 - GCS + eltrombopag 1 - GCS + azathioprine Results and Discussion Average duration of the laparoscopic SE was 109 min (from 50 to 250 min), on the average 100 min with the mean blood loss of 300 ml (median 200 ml). In 20 patients intraoperative blood loss was negligible, in 14 – over 500 ml. In patients treated with only corticosteroids blood loss over 500 ml was in 16%, in pretreated- in 20%. Intraoperative complications (5.7%): • pneumothorax-1 • intraoperative bleeding led to conversion-2 • acute respiratory failure-1 • bleeding from the bed of the spleen, stopped by conservative measures-1 Postoperative complications occurred in 13,8% (n = 12): •patients treated with corticosteroids 11.3% •patients receiving multiple lines of therapy - 24%. •thrombotic complications (3.4%) •portal vein thrombosis 1 •tibial vein thrombosis 1 •ischemic stroke 1 •pneumonia 8 (9%) •intestinal bleeding-1 (1.1%) In 13 (14.9%) patients, operated on with thrombocytopenia < 20x109/l, average blood loss was 320 ml (100-1200 ml). The operation was complicated in 2 patients by intraoperative bleeding required conversion. One patient in the postoperative period developed acute adrenal failure, pneumonia, septic shock. In 49 (56.3%) patients, operated on with thrombocytopenia 20-100x109/l, mean blood loss was 240 ml (0-1100 ml). Postoperative complications developed in 7 (14%) of them (1 portal vein thrombosis, acute respiratory failure 1, pneumonia 5). In 26 (29.8%) patients, operated on with the platelet count of more than 100x10, average blood loss was 370 ml (0-2000 ml). One intraoperative complication - injury to the diaphragm. Postoperative complications (1 bleeding, pneumothorax, 1, 1 pneumonia, thrombosis of the saphenous veins of the lower extremities 1) developed in 4 (15%) pts. In 69 patients with the duration of the disease over 6 months the efficiency of SE was 84%. In 17 patients with the duration of the disease less than 6 months - 70.6%. In patients treated with corticosteroids, efficiency of SE was estimated as 85.5% In pretreated - 60%. Nonefficient SEs were observed in 10 pts. In 10 patients the platelets count after SE remained Administration of romiplostim (n = 7) led to an increase of the platelets count up to 60-80 x 109/l in 7 patients (100%) in the first week after surgery Conclusion • SE results in a full or partial response in 79.6% of patients with ITP • Optimal time for SE is 6 - 12 months after the onset of the disease • Risk of complications of the procedure increases with the delay of SE • A history of multiple lines of drug therapy reduces the efficiency of SE in ITP from 79.6% to 60.0%. Disclosures No relevant conflicts of interest to declare.

BACKGROUND: Follicular lymphoma (FL) is one of the most frequent types of B-cell lymphomas and accounts for about 22% of all non-Hodgkin lymphomas in Russia. The disease is usually a long-term condition with frequent relapse. At the same time 15-20% of pts have fast-tumor progression. Patients (pts) of this group die within the first 1.5-2 years from the time of diagnosis. High-dose chemotherapy (HDT) followed by ASCT in the presence of nonfavorable characteristics of FL (fast growth of tumor volume, B-symptoms, third citological grade of tumor, large tumor size, absence of anti-tumor response to R-CHOP courses in the first remission) increases the overall survival and progression-free survival of pts. AIM: To estimate HDT with ASCT efficiency among pts with FL in front-line therapy who received treatment in the National Research Center for Hematology during 2000-2013. PATIENTS AND METHODS: The results of ASCT among 12 pts with FL have been analyzed: 8 male and 4 female aged from 31 to 50 with median age 43. Patients in the main group (11/12) were on the IVth stage of tumor growth. In 6/12 cases the tumor size was more than 6 sm. Among 7/12 pts, besides lesions of lymphatic nodes, extra nodal lesions were found: infiltration in psoas (1/12), kidney (1/12), stomach (1/12), lungs (1/12), thyroid (1/12), pancreas (1/12). In 2/12 cases leukaemization was observed. Based on FLIPI criteria all the pts were divided into three groups: in the first risk group - 5/12 pts, in the second - 3/12, in the third - 4/12. B-symptoms were in the majority of cases (9/12). 9/12 pts were diagnosed with I-II cytological grade of FL, among 3/12 - III A/B. Based on the character of tumor growth the dispersion was the following: nodular tumor growth - 5/12, nodular-diffuse tumor growth-6/12, diffuse tumor growth - 1/12. Immuno-chemical investigation of protein serum and urine was performed in 9/12 cases, and among them rising serum β2-microglobulin above the norm was observed in 4/9 pts. A rise in lactate dehydrogenase concentration above the norm was observed among 4/12 pts. Lesion of bone marrow at the beginning of the disease was identified among half of the pts (6/12). Induction courses were performed on the R-CHOP programs, with intensive therapy - on protocol mNHL-BFM-90. RESULTS: Anthracycline courses were prescribed for nearly all of the pts as an inductive therapy: R-CHOP (11/12). mNHL-BFM-90 protocol was chosen as an inductive regime because of the fast growth of tumor size, IIIB grade of FL in 1/12 case. This tumor growth behaved like diffuse large B-cell lymphoma. In three cases medical-diagnostic splenectomy was undertaken before chemotherapy. After the inductive regimes the pts were given HDT based on the following scheme: two courses R-DHAP, course with rituximab and high-doses cyclophosphamide, a course with rituximab and high doses of etoposide, R-BEAM. All 12 pts, who were given ASCT are in full remission on the main disease. The period of observation is from 13 to 164 months. CONCLUSION: This first experience of intensive therapy in FL in Russia demonstrates that ASCT as a front-line therapy leads to complete remission of FL among pts who have nonfavorable prognosis factors. Disclosures No relevant conflicts of interest to declare.

Introduction. Most studies have found that hyperleukocytosis (HL >100*109/l) is a poor prognostic factor in acute myeloid leukemia (AML). It is diagnosed in 5-13 % of cases and is more common in AML with monocytes’ differentiation (M4, M5), as well as in cases with poor prognostic molecular markers, such as FLT3-ITD and others. According to the literature the early (during the first week) mortality in AML due to HL may reach 90%. The main cause of death are leukostasis, leading to neurological symptoms, respiratory distress syndrome (RDS) with lung lesions, disseminated intravascular coagulation (DIC) syndrome with the development life-threatening bleedings and massive tumor lysis syndrome during induction therapy. Aim. National Research Center for Hematology (NRCH) has initiated a prospective clinical study aiming to develop a feasible clinical approach preventing severe tumor lysis syndrome during induction in AML patients with initial WBC >100*109/l by using serial plasmapheresis (PA). Patients and Methods. From Jan 2010 till June 2014, 92 patients with de novo AML were treated in the NRCH according to AML-10 protocol (ClinicalTrials.gov Identifier: NCT01587430). Initial white blood cell (WBC) count more than 100x109/l was detected in 18 patients (19,5%): median age - 38 y (17-56yy), M/F - 10/8, WBC - 130x109/l (100-408x109/l), LDH -1765 µ/l (720-6653). 2 patients were in the favorable, 13 – in the intermediate, 2 - in the poor cytogenetic risk group. 83,3% (15/18) patients had hepatosplenomegaly and lymphadenopathy, 38.8 % (7/18) - gingival hyperplasia, 16,6 % (3/18) - neuroleukemia, 16,6% (3/18) - skin leukemids. All patients had infectious complications at diagnosis. Lung infiltrates due to leukostasis were revealed - in 77,8% (14/18), including 5 patients (27,8%) with RDS; neurological symptoms (headache, blurred consciousness) - in 33,3% (6/18), DIC syndrome - in 8/18 (44,4%) with 1 intracranial hemorrhage. All patients received allopurinole 600 mg/day. PA procedures were started during cytoreductive therapy (hydroxyurea 10 mg/kg/day 1-2 days) sometimes with leukapheresis (LA) and were continued within 1 or 2 days of conventional 7+3 (ARA-C 100 mg/m2 bid iv 1-7 d, DNR 60 mg/m2 x 3d) 2 hours after short (30 min) ARA-C infusion. DNR was applied on days 3 to 5 or 5 to 7, thus PA did not interfere with its pharmacokinetic properties. All patients concomitantly have got intensive hydrating (3-4 l) and diuretic therapy with electrolytes and albumin support. Results: Cytoreductive therapy with hydroxyurea was used for a median 2 days (1-7 dd). Half of the patients (9/18) have got 1-2 procedures of LA (median 2). Median 2 (1-4) procedures of PA were performed in 17/18 patients. The volume of removed plasma for 1 PA procedure was 1200 ml (900-1500 ml), the volume of compensation was – plasma 1100 ml (500-1600 ml) +/- 20% albumin 50-150,0 and 0,9% NaCl 500-1000,0. Median WBC count after cytoreductive therapy at the 1st day of 7+3 was 60x109/l (5,6-124x109/l). DNR was administered on days 5-7 in 16 and on days 3-5 - in 2 patients. No severe cytolysis with the development of multiple organ failure was observed. Only 1 patient with massive extramedullary involvement has developed just laboratory signs of acute renal failure without stopping the urinary function. Less than third of the patients (5/18) developed the transient signs of volemic overload within the first days of chemotherapy treated successfully with diuretics and plasmapheresis. CR after the 1st induction was achieved in 50% of (9/18) patients. Additional 7 patients achieved CR after the 2nd induction, resulting in 89% overall CR rate. Only 1 patient (5,5%) died with severe infectious complications during aplasia. Allogeneic bone marrow transplantation was performed in 8 of 16 CR patients. The median OS and DFS was 28 and 23 months, 3-years OS and DFS was 32% and 35% respectively. Conclusions. Our small study brought us to a conclusion that serial PA procedures during cytoreductive phase and the first days of 7+3 may prevent the development of tumor lysis syndrome and its complications. This clinical approach is feasible, easy to perform and decreases early mortality. Disclosures No relevant conflicts of interest to declare.

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 30 for B-lineage, >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.

Introduction. The vast majority of AML clinical trials incorporate high-dose ARA-C (HDARA-C) as a basic approach. Though it was recently proved by a controlled prospective comparison that different treatment strategies in patients with AML did not show clinically relevant outcome differences (Th.Buchner, JCO, 2012), the RALSG initiated a randomized multicenter AML-10 trial (ClinicalTrials.gov Identifier: NCT01587430) aiming to evaluate the necessity of HDARA-C in consolidation in the context of high total dose of different anthracyclines/anthracenedione (660-720 mg/m2). Materials and methods. The patients aged 16-60 yy with de novo AML (except APL) were randomized before treatment start to different types of consolidation after two induction 7+3 with daunorubicin 60 mg/m2x3 and ARA-C 100 mg/m2 bid iv (1-7d) in the 1st course and 200 mg/m2/d (1-7d) continuous infusion in the 2nd course: (1st arm) two courses of 7+3 with Idarubicin (Ida) 12 mg/m2x3 and with Mitoxantrone (Mito) 10 mg/m2x3, in both ARA-C 100 mg/m2 bid iv (1-7d); (2nd arm) two courses of HDARA-C 1g/m2 bid iv 1-3 days with Ida 8 mg/m2 3-5 days and Mito10 mg/m2 3-5 days. After consolidation all pts proceeded to the maintenance 5+5 courses (ARA-C 100 mg/m2 bid iv 1-5 days with 6-mercaptopurine 50 mg/m2 1-5 days). Allogeneic HSCT was indicated to patients from intermediate and poor cytogenetic risk groups, late CR, WBC > 100*109/l. Results. From Jan 2010 till Jan 2014, 250 AML patients from 20 centers were randomized: (1st arm) 125 pts (m.age 45 y, 17-59 yy; 73f / 52m; LDH=674 IU (128-6653); cytogenetics favorable - 17,3%, intermediate - 66,7%, poor - 16%) and (2nd arm) 125 pts (m.age 43y, 16-60yy; 69f/56m; LDH=704 IU (123-8159); cytogenetics favorable - 20%, intermediate - 58,6%, poor - 21,4%). No molecular testing in cytogenetically normal pts was done. The analysis was performed in May 2014. The follow-up data were available in 199 pts. CR was achieved in 72,9% (n=145), early death was registered in 12,7% (n=25) and refractory disease - in 12,4% (n=24). Death in CR did not differed in a randomized groups (1st) 13,9% and (2nd) 13,7%. 17% of CR pts (n=20) were withdrawn from the protocol due to refusals (3,5%), infectious complications (13,5%). No relevant cardiotoxicity was registered on both arms. 12% (8 pts on the 1st arm, 9 - on the 2nd) were transplanted in 1st CR from HLA-identical donors. 3-years OS and DFS by intent-to-treat analysis were identical on both arms: (1st arm) 43% and 62%, (2nd arm) - 38% and 51%, respectively. For those patients in whom consolidation was fulfilled the comparison of DFS in different cytogenetic groups demonstrated equal efficacy of each consolidation arm: favorable - 85% (1st) and 85% (2nd), intermediate -65% (1st) and 57% (2nd), poor - 20% (1st) and 22% (2nd). In a multivariate analysis only cytogenetic group (HR=3,01, p=0,005) and CR achievement after the 2nd induction course (HR=2,83, p=0,0007) adversely influenced DFS. As the land-mark (5 mo of CR) analysis have shown, the bad prognosis of late CR could be modified by allo-HSCT in 1st CR: DFS of transplanted patients = 86%, non-transplanted=27% (p=0,03). Conclusion. Our interim analysis has demonstrated that conventional 7+3 consolidation is equal in long-term outcome to high dose ARA-C in case of the high total doses of different anthracyclines/ anthracenedione in induction/consolidation. CR after the 2nd induction became independent adverse prognostic factor (even inside cytogenetic risk groups) defining patients who should be transplanted in 1st CR. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Introduction Allogenic bone marrow transplantation (allo-BMT) with high-dose, post-transplantation cyclophosphamide (CY) to promote graft-host tolerance has become an alternative for standard immunosuppression. This post-BMT CY-based immunosuppression regimen has comparable efficacy with other immunosuppressive regimens including cyclosporine A and mycophenolate mofetil. Previously we reported a significant reduction of acute GVHD rate by using MSC infusion for GVHD prophylaxis (n=19, p=0.009) [Abstract 1256, 52nd ASH Annual Meeting abstract]. So we studied high-dose, post-transplantation cyclophosphamide and mesenchymal stem cells (MSC) infusion for graft-versus-host (GVHD) prophylaxis for patients with advanced disease after FLAMSA (where amsacrin was substituted for idarubicin) and FluBuATG conditioning regimen. Patients and methods 7 patients with a median age 38 years (24-59 years; 5 males, 2 females; 4 donors/recipient pairs was sex matched, 3 was sex mismatched). All patients with advanced disease (relapsed or refractory AML n=4, ALL n=2, MM n=1) with a median blast cells 17.4%, underwent allo-BMT (n=5 from HLA-identical related donor, and n=2 from unrelated donor). Conditioning regimen was composed of fludarabine, busulfan, and horse anti-thymocyte immunoglobuline for 2 patients, in 4 patients FLAMSA was applied, and 1 patient has no conditioning regimen at all (he was in profound prolonged aplasia after previous course of chemotherapy). For GVHD prophylaxis CY at dose 50 mg/kg daily at day +3 (n=2) and at day +3,+4 (n=5) was used. All patients also received MSC for acute GVHD prophylaxis at day of recovery (WBC>1*109/l) at dose 1*106/kg. No other immunosuppression was used. Results Neutrophil engraftment was achieved at a median day +20 (range from 17 to 44 days). Acute GVHD occurred in 3 patients (43%) at a median day +45; all cases were Grade 2-3 (with only skin n=2; and with skin and liver involvement n=1); there was only 1 patient with late refractory GVHD in this study treated with prednisone at a dose 2 mg/kg; all other patients responded to initial treatment with cyclosporine A at 3 mg/kg. Overall mortality rate was 42.6%. 1 patient died in CR at day +60 due veno-occlusive disease (TRM - 14%). Relapses occurred in 2 patients (28.6%) at a 3,8 and 2.4 months. The overall survival is 51.4% with a median of follow-up 3,9 month. Conclusion Despite the fact that we study small group use of cyclophosphamide with MSC for GVHD prophylaxis is a very attractive approach for patients with advanced disease, and needs further investigation. Disclosures: No relevant conflicts of interest to declare.

Background Bone marrow involvement occurs in 10–20% of cases of diffuse large B-cell lymphoma (DLBCL). According to its morphological characteristics bone marrow involvement can be concordant (CBM) or discordant (DBM). DLBCL with bone marrow involvement (DLBCL BM) is characterized by aggressive course and poor response to standard polychemotherapy, with the worst results observed in the group of patients with CBM: 5-year overall survival rate is less than 10%. Application of the mNHL-BFM-90 treatment program in DLBCL BM patients resulted in only partial remission. In many cases there was persistent residual bone marrow infiltration, whereas the tumor fully regressed in other locations. In these cases it seemed reasonable to apply consolidating high-dose sequential chemotherapy (sHDT) and autologous stem cells transplantation (ASCT). Aim To evaluate the efficacy of the mNHL-BFM-90 treatment program with sHDT and ASCT in DLBCL BM patients. Patients and Methods We performed a pilot prospective trial, including 15 consecutive adult patients (median age 44 years, range 23–57, female=4, male=11, CBM=5, DBM=10) with newly diagnosed DLBCL BM who were treated with sHDT and ASCT as a part of the mNHL-BFM-90 program from Feb 2005 till July 2013. All patients underwent 4 courses of mNHL-BFM-90 chemotherapy program, including A blocks (methotrexate 1,5 g/m2 day 1, ifosfamide 800 mg/m2 days 1–5, vincristine 2 mg day 1, doxorubicin 50 mg/m2 day 3, etoposide 100 mg/m2 q 12 hrs days 4–5, cytarabine 150 mg/m2 q 12 hrs days 4–5, dexamethasone 10 mg/m2 days 1–5) and C blocks (methotrexate 1,5 g/m2 day 1, cytarabine 2 g/m2 q 12 hrs days 2–3, vinblastine 10 mg/m2 day 1, etoposide 100 mg/m2 q 12 hrs days 4–5, dexamethasone 10 mg/m2 days 1–5). After 4 induction courses patients continued receiving treatment according to the sHDT scheme, including 2 DHAP courses and 3 high-dose courses with the hematopoietic stem cells (HSC) mobilization and collection: cyclofosfamide 4 g/m2 day 1, methotrexate 8 g/m2 day 15 and vincristine 2 mg day 15, etoposide 500 mg/m2 q 12 hrs days 31–34. In cases of sufficient quantity of collected CD34+ cells (≥ 2x106/kg), the BEAM conditioning and the ASCT were applied. The programed therapy was fully implemented in 6 out of 15 patients. The average amount of harvested HSC was 4x106/kg (range 2–7,2x106/kg). Due to unsufficient HSC collection, ASCT was not carried out in 9 patients. If complete remission (CR) was achieved only after sHDT, one additional Dexa-BEAM course was carried out (4 patients). The other patients completed the therapy after the sHDT (5 patients). The rates of overall survival (OS) and probability of relapse were estimated (±SE) by using the Kaplan-Meier method. Statistical analysis was done using JMP ver. 10.0 (SAS, Cary, NC). Results Two patients achieved CR after 4 courses of chemotherapy program mNHL-BFM-90, while the other 13 patients achieved PR; however, they had residual disease only in the bone marrow. All patients achieved CR after sHDT therapy. There were 2 patients with early relapse (8 months): one of them had CBM and another had DBM. One of these cases of relapse was registered in patient after ASCT. Remission has been maintained in 4 of 5 patients with CBM. There were no cases of death from the chemotherapy toxicity. At the median 44 months (range 19–95) follow-up the overall survival was 82±12%, and probability of relapse was 15%. Conclusions DLBCL with bone marrow involvement has a very poor prognosis with the CHOP-like therapy, and we consider it as the basis for high-dose chemotherapy. Our trial showed that the long persistence of the tumor in the bone marrow requires the prolonged treatment. The primary-intensive mNHL-BFM-90 treatment program with the sHDT and ASCT was used for the first time in the DLBCL BM patients, including patients with CBM, and has shown high efficacy. Disclosures: No relevant conflicts of interest to declare.

Relapses after allogeneic stem cell transplantation (allo-SCT) are the main cause of treatment failure in acute myeloid leukemia (AML). Chemotherapy with subsequent donor lymphocyte infusions (DLI) is considered to be the optimal approach for complete remission (CR) achievement and induction of “graft versus leukemia” effect. There is a tendency to use low-dose chemotherapy (i.e. Low-dose Ara-C) in this setting because of less toxicity. However the efficacy of low-dose chemotherapy is not satisfactory and leads to 45-67% CR rate. In this study we apply intensive chemotherapy (7+3) followed by DLI in aplasia in with relapsed AML. Aim To investigate the efficacy of DLI perfomed in neutropenia after reinduction chemotherapy 7 +3 (Cytarabine 100 mg/m^2 every 12 hours daily for 7 days, and Idarubicin 12 mg/m^2 daily on days 1, 2, and 3) in AML patients (pts) with overt relapse after allo-SCT. Methods The study comprised 16 AML patients. The median age was 31 years (16 - 57 years), male – 11 female - 5. Twelve patients underwent allo-SCT in first remission, 4 pts - in overt relapse of AML. Allo-SCT was carried out from HLA-matched sibling donor in all pts. Myeloablative conditioning regimen was performed in 10 pts. Reduced intensity conditioning (RIC) - in 6 pts. AML relapse occurred at a median 4,7 months (range from 1 to 51 months) after allo-SCT. Patients received DLI at day 7 (7-14 days) after chemotherapy during myelotoxic agranulocytosis. The number of infusions ranged from 1 to 4 (median 2 DLI) per patient. DLI after chemotherapy were carried out twice in 1 patient due to the second relapse. So we analysed 17 cases of relapse in 16 pts. Total amount of the CD3+cells varied from 1 to 16,7x10^7 CD3+cells/kg (median 6,0x10^7 CD3+ cells/kg). The interval between DLI was 1-4 weeks. All pts received 2 - 6 MUE Interleukin-2 (IL-2) subsequently after DLI. Chimerism was monitored by PCR analysis (VTTR and STR) and by FISH – analysis for centromers of X and Y – chromosomes after DLI each 2-4 weeks up to 6 months, then every 3 months. Results Complete remission with 100% donor chimerism was achieved in 14 (82%) out of the 17 cases. There were no toxic deaths, 3 pts died in leukemia progression. All pts developed severe infections in neutropenic phase (mucositis, pneumonia, sepsis), but they were cured. Eight pts (57%) out of 14 developed a relapse in 5 months after DLI (from 1 to 17 months) and 6 pts (35%) remained in remission. Follow-up period was 12 months (1 - 124 months). Median overall survival constituted 15 months. Acute graft versus host disease (GVHD) after DLI was diagnosed in 8 patients 47% (6 - I-II grade; 2 - III-IV grade). Chronic GVHD was diagnosed in 8 pts (47%): limited -6 pts (35%), extensive - 2 pts (12%). Conclusion Our data show that despite myelotoxicity and infections 7+3 and subsequent DLI+ IL-2 is an effective treatment for AML pts with overt relapse after allo-SCT. Disclosures: No relevant conflicts of interest to declare.

Background Splenectomy (SE) at the Myelofibrosis (MF) is one of the difficult operations on the techniques and perioperative complications. There are a lot of complications such as inflammatory and adhesive processes, a massive bleeding associated with disorders of hemostasis in thrombocytopenia or thrombocytosis, enlargement of varicose veins, concomitant pathology. A SE doesn’t cure myelofibrosis but may be performed in some cases. Success is unpredictable, and the operative mortality of SE is on the order of 10%. Objectives Evaluate the clinical and hematologic SE efficiency in patients with MF, resistant to traditional treatment. Patients and methods We analyzed the medical case history of 52 patients with MF, which were observed in the National Research Center for Hematology from 2004 to 2013. All patients were performed SE. 47 patients diagnosed with primary MF, and 4 – post-polycitaemic MF and 1 patient post-trombocitaemic MF. PMF was diagnosed according to the criteria established by WHO (2008), which include bone marrow fibrosis, and splenomegaly leyko-eritroblastosis in peripheral blood. The average age at diagnosis was 47 years (24 – 78 years), and before the SE – 53 (25 – 79 years). Women and men ratio was 1.3:1. According to the predictive model of the Dynamic International Prognostic Score System - (DIPSS) 38 (73%) patients before the SE attributed to intermediate risk 2, 14 (27%) patients – high risk. BCR-ABL gene not found a single patient, and the gene mutation JAK2V617F at different stages of the disease is detected in 53% of cases. Genetic adverse factors are not taken into account because of the small number of studies. Massive and huge splenomegaly was present in 37 (71%) patients. Spleen weight 0.9 to 2.9 kg is removed in 15 (29%) patients, from 3 to 7 kg is removed in 35 (67%) patients. In two cases, removal of the spleen weight of 10 and 11 kg. Statistical analysis were done using SAS 9.3 and JMP 10.0 (SAS Institute Inc., Cary, NC). Results Disease duration was about 76 months and ranged from 1 to 240 months. Surgical complications occurred in 21 patients, including bleeding 3, thrombosis 1, infection 2. Surgical complications from SE in intra-and early postoperative period was 8% from 1978 to 2003. Surgical complications from SE in intra-and early postoperative period was not fixed from 2004 to 2013. After SE complications were hepatomegaly, resistant thrombocytosis (platelet count ≥ 600 × 109/L), leukocytosis (white blood cell count greater than 10 x 109/l) and blast transformation of the disease. More than 80% of patients after SE had no symptoms of intoxication. 22 patients with MF had transfusion dependent anemia, 11 (50%) had disappeared transfusion requirements after SE in and the effect lasted for about a year. Only 4 of the 15 patients with thrombocytopenia who underwent SE due to refractory thrombocytopenia were observed a significant increase in platelet count above 100h109 / L, for an average of 6 months. The possibility of the resumption of long-term cytoreductive therapy appeared in 30 (58%) patients. Currently alive 19 (37%) patients, mean follow-up was 37 months (4 to 72 months) after the SE and of 105 (12-264) months after diagnosis. 33 (63%) patients died during the observation period after SE (1 – 84 months, mean – 27 months). Among these, 27 (82%) patients died of transformation disease and 6 (18%) died of comorbidity. 19 (37%) patients, with a mean follow-up of 37 months after SE (from 4 to 72 months) continue treatment with hydroxyurea. Median survival after SE is 3 years (Figure 1), with a median overall survival - 11 years (Figure 2). Conclusion Despite the potential complications SE is an effective palliative method for patients with MF in the absence of leukemic progression. SE indicated in patients with drug refractory MF, acute constitutional symptoms, anemia, transfusion-dependent, and portal hypertension. Modern methods of surgery, as well as supporting therapy in the perioperative period can safely perform the SE. Disclosures: No relevant conflicts of interest to declare.

Abstract 2034 Background: Mantle cell lymphoma (MCL) is aggressive B-cell neoplasm diagnosed predominantly among elderly men. (R)CHOP-like schemes are effective in remission induction, but the progression-free survival is disappointingly short (median 16–20 months) with median overall survival of 3–4 years. Upfront use of high-dose cytarabine (12 g/m2), autoSCT and rituximab at all stages of therapy is the most effective treatment but possible only with patients younger 65 years. Decrease in AraC doses to 4 g/m2 per cycle significantly reduce progression free survival. Prominent efficacy of gemcitabine-oxaliplatin combinations and irinotecan in relapsed and refractory MCL patients allowed including these drugs in first-line treatment in cases when the scheme R-HD-Met-AraC (Romanguera J. 2005) is impossible. Aim: Toxicity and efficacy assessment of schemes R-DA-EPOCH/R-GIDIOX and R-DA-EPOCH/ R-HD-Met-AraC in primary MCL patients eligible for autoSCT. Patients and Methods: Since May 2008 35 untreated MCL patients (median 55 years (29–63), males/females 68,5%/31,5%, MIPIb: 34% low, 26% intermediate, 40% high risk) were enrolled. After first R-EPOCH course (Wilson W. 2003) patients were stratified according to toxicity they had received either R-DA-EPOCH/R-HD-Met-AraC or R-DA-EPOCH/R-GIDIOX. In the absence of hematological toxicity grade 4 for more than 3 days, severe infection complications and signs of renal failure patients underwent treatment under the scheme R-HD-Met-AraC (rituximab 375 mg/m2 day 0, methotrexate 1000 mg/m2 24 hours CI day 1, cytarabine 3000 mg/m2 q 12 hrs days 2–3). If there was one of these complications patients underwent treatment under the scheme R-GIDIOX (rituximab 375 mg/m2 day 0, gemcitabine 800 mg/m2 days 1 and 4, oxaliplatin 120 mg/m2 day 2, irinotecan 100 mg/m2 day 3, dexamethasone 10 mg/m2 IV days 1–5, ifosfamide 1000 mg/m2 days 1–5). Further these courses are rotated: either R-DA-EPOCH/R-HD-Met-AraC or R-DA-EPOCH/R-GIDIOX. Depending on the terms of response, patients received 6–8 courses (3–4 cycles) of chemotherapy and autoSCT (BEAM-R) with in vivo purging by rituximab before harvest and reinfusion. Patients with residual tumor after autoSCT were consolidated with local radiotherapy. Rituximab maintenance was performed every three months for 3 years. The protocol was approved by the local ethics committee. Patients were analyzed in an intent-to-treat basis. Overall survival (OS) and event-free survival (EFS) rates were estimated (± standard error) by using the Kaplan-Meier method. Efficacy of the therapy was assessed by Cheson's response criteria (2008). Toxicity assessment was performed 93 R-DA-EPOCH, 60 R-HD-Met-AraC and 46 R-GIDIOX courses. Results: A median follow-up is 23 months (range 3–54). Toward August 2012 26 patients underwent autoSCT: 14 from R-HD-Met-AraC arm and 12 from R-GIDIOX arm. 1 induction death after first HD-Met-AraC course (acute renal failure and septic shock). Maintenance therapy with rituximab was completed in three patients. All patients achieved CR in R-HD-Met-AraC arm. In R-GIDIOX arm OR was 100%: 11 CR and 1 PR (without progression for 26 months after autoSCT). Main non-hematological toxicity of R-GIDIOX was hepatic, with elevated aminotransferases grades 1–2 and 3–4 in 59,5% and 7,1% of courses respectively, without clinical signs. The sources of stem cells were PB in 23 patients and BM in 3 cases of harvest failure after R-GIDIOX. Hematological toxicity of R-GIDIOX course: leukopenia grade 4 was in 71,4% (medium duration was 5,4 days, range 1–13), thrombocytopenia grade 4 was in 42,9%. The estimated 4-years OS rates for the R-GIDIOX group and the R-HD-Met-AraC group were 100% and 68% ± 17%. The estimated 4-years EFS rates for the R-GIDIOX group and the R-HD-Met-AraC group were 90% ± 10% and 69% ± 14%. Conclusions: Our main goal was to incorporate intensive induction, autoSCT and rituximab maintenance in first line therapy MCL patients. However, HD-Met-AraC scheme is highly toxic and its use is possible only in 2/3 of patients younger 65 years. R-GIDIOX scheme is less toxic than R-HD-Met-AraC and equally effective in response induction and mobilizing, so it could be recommended for those in whom high-dose AraC and methotrexate can potentially cause severe adverse consequences. Such an integrated approach might lead to a shift of paradigm of MCL from an incurable to a curable lymphoma. Disclosures: No relevant conflicts of interest to declare.

Abstract 1879 Splenectomy in patients with MDS is a treatment option that is beeing applied very rare [Steensma D., et al, Leuk Res.,2003; Bourgeosis E., et al, Leukemia, 2001]. There are anecdotal reports with very few patients demonstrating its efficacy. In most cases splenectomy was indicated for MDS patients with immune related thrombocytopenia. Here we would like to report the results of 33 splenectomies in patients with MDS who have been treated in our Center during 1994–2010. Within this period of follow-up totally 155 patients were diagnosed with different forms of MDS, 35% of them presenting with hypoplasia. The MDS treatment algorithm in our Center incorporates splenectomy as one of the options for pts with hypoplastic forms of MDS with bone marrow blast count less than 10%, refractory to initial cyclosporin A treatment or refractory to transfusions. Among patients who were splenectomised there were 20 females, 13 males with a median age of 40 years (range 18–74). Median time from diagnosis to splenectomy was 12 months (range 4–107). By WHO-classification there were 2 patients with RA, 22 – with RCMD, 2 – with MDS and del (5q), 6 - with RAEB, 1 - with AML after MDS. Cytogenetic analysis was available in 32 cases, and karyotype was normal in 15 patients (47%).The most common abnormalities were: del (5q) - 3, del (20q) - 2, trisomy 8 - 2, tetrasomy 8 - 1, monosomy 7 - 2, complex karyotype - 4. Bone marrow biopsy revealed hypoplasia in 25 patients (75%), myelofibrosis – in 7 (21%). The median WBC count was 2,6*109/L (range 0,6-8,7), hemoglobin 6,9 g/dL (47-119) and platelets 26*109/L (6-170). 27 pts (82%) were RBC transfusion dependent, 22 (67%) - platelets transfusion dependent. 13 pts had received immunosuppression therapy (ATG, cyclosporine A) before splenectomy, 2 - cytotoxic chemotherapy, 3 - decitabine. The majority of splenectomies were done by laparoscopic method - 26 (79%), in one case the convertion was done. In all cases we performed liver biopsy. Postoperative complications (hemorrhage) occurred in 1 patient but there were no deaths due to operation. One death occurred in 7 days after splenectomy due to fulminant progression to AML. Median spleen weight was 180 gms (range 70–930). Median intraoperative blood loss was 250 ml (range 50–9350). Histology was available in 30 patients. Extramedullary hematopoesis was revealed in 3 cases (10%), blast infiltration - in 2 (7%), massive lymphoid infiltration was detected in 5 cases and in one patient in was proved to be clonal (marginal zone lymphoma, MZL). Hemosiderin depositions in the macrophages were seen in half of the cases -16 (53%). One case was characterized by granulomatosis in spleen and liver with negative immunohistohemical staining to Mycobacteria tuberculosis. Splenectomy lead to sustained improvement of cytopenias in 16 cases (48%): decreased transfusion dependence in 14 (42%) and transfusion independence in 2 (6%). After splenectomy 5 patients were followed by “wait and see” approach, 17 continued with immunosuppressive therapy (ATG,CyA), 3 patients were treated with cytotoxic chemotherapy, 1 – with decytabine, 2 received EPO, 1- danazol, 2 - iron chelation therapy, 2 – only transfusions therapy. We did not noticed the infections rate augmentation after splenectomy. Transformation to AML was registered 6 (18%) at median 6 months (0,3 -9). 13 splenectomized patients (39%) died at a median 12 months (range 0,3-84) and the main death reasons were: AML progression, aplasia deterioration followed by infections and hemorrhage. 20 patients are alive with a median follow-up after splenectomy 33 months (2-108). Analysis of our 15-years study data give us a confidence to conclude that splenectomy still may be an adequate option for distinct forms of MDS (hypoplastic forms with bone marrow blast count less than 10%, refractory to initial immunosupressive treatment or refractory to transfusions), producing cytopenia improvement in half of the patients with decreasing transfusion dependance also in half of the patients, sometimes bringing a clear diagnosis (MZL). The mechanism of action is not very clear but we can speculate that splenectomy removes the “cell-destroying” organ, deminishes immune pathways of cytopenias due to large lymphoid compartment deletion, provides the resustainment of sensitivity to immunosupressive agents. Disclosures: No relevant conflicts of interest to declare.

Donor lymphocyte infusions (DLI) are considered to be the treatment of choice in pts with relapses after allogeneic hematopoietic stem cell transplantation (HSCT). This kind of treatment is based on alloreactivity of donor lymphocytes, mediating a graft-versus-leukemia (GVL) effect. However, the relapses of acute leukemia in many cases are not susceptible to DLI. There were few reports that the concominant administration of cytokines (IL-2, IFN-alfa) and DLI is more efficient for conversion to complete donor chimerism (CC) from mixed chimerism (MC) and leads to remission in pts relapsed after HSCT, but the significance of this therapy is still not estimated. The aim of study was to evaluate the efficacy of DLI treatment combined with IL-2 i.v. administration for CC establishment and remission induction in pts with relapses after HSCT for hematological malignancies. 26 pts were treated with DLI for relapses after ASCT from related siblings in 2001–2007. 12 of them were included in the study. Median age was 25 y (16–44), 9 men/3 woman, 4 pts with AML, 1 - APL, 1 - ALL, 1 -ANL, 3 -CML, 2- MDS. 2 pt received reduced intensity HSCT, 10- conventional one. Median time to relapse was 12,5 months (3,5 – 48 months).10 pts demonstrated hematological relapses, 1 pt with APL and 1 pt with CML - molecular relapses. All pts with AL in overt relapse received chemotherapy first and then DLI was performed in aplasia. CML pts were treated with Hydrea and Glivec and then DLI were administrated. Median dose of infused DL was 6,34 x 108/kg (median 6 transfusions per pt) with median of CD3+ cells. Chimerism status was investigated on BM and PB using VNTR/STR analysis at relapse, before every DLI and monthly after DLI completion. All pts demonstrated MC in bone marrow before chemotherapy (median 74% of host DNA). 9 pts were still MC after chemotherapy and before DLI (median 38% of host DNA), 3 pts became CC before DLI. In all pts DLI were combined with IL-2 (2–6 MU with every DLI). In 6 pts with MC after chemotherapy only 1 (with CML) became CC after 1 course of DLI and developed aGVHD II–III and then cGVHD. 5 pts (with AL and MDS) after DLI were still MC remaining in hematological remission. One of them died of CMV infection. 2 pts recieved the 2nd course of DLI + IL-2, became CC and are still well and alive (1 - with cGVHD, 1 - without GVHD) for 30 months. For 2 pts (AML) with MC 2nd DLI course was not possible (donor was not available) and they received the course of IL-2 (5 days for 6 MU daily) in 2 months after DLI. The both are in complete remission with CC and cGVHD. 4 pts showed no effect and soon relapsed despite the 2nd DLI course in 2 pt and 2nd course of IL-2 in 1 pt. Despite the small and heterogenious group we may conclude, that DLI administration concomitantly with IL-2 leads to more prominent GVL effect and quick conversion from MC to CC. The interesting observation is that the additional infusions of IL-2 were effective for conversion to CC and remission induction in 3 of 4 pts resistant for DLI.

Russian Leukemia study group is presenting the final analysis of the APL-06.01. randomized clinical trial. The aim of the study was to identify the efficacy of ATRA substitution of each other chemotherapy course while the 2-yrs maintenance after three induction/ consolidation 7+3 with daunorubicin dose of 180 mg/m2 per course and ATRA for 30 days while the first induction. The patients were randomized for two types of maintenance - (I type) rotation of 5-days ARA-C (100 mg/m2 bid) combined with daunorubicin (45 mg/m2 for 2 days, till the total dose of 650 mg/m2) or 6-MP (50mg/m2 p.o.5 days) or CHP (800 mg/m2 i.v.1 day) or (II type) rotation of the same courses of chemotherapy with 5-days 45 mg/m2 ATRA course. The II type of maintenance treatment contained twice less chemotherapy. The intervals between courses were 4 weeks From July, 2001 till January, 2006 114 APL patients from 26 centers were enrolled in the study. In 95% of pts APL was confirmed by cytogenetics or PCR. 102 patients were included in the analysis. CR rate was 85%, ED rate -15%, 4-yrs OS -68,3%, DFS - 77,4%, CCR - 89,5%. Suvival analysis according to randomization did not demonstrate statistical differences, but showed a trend (p=0,06) towards better DFS and CCR in patients maintened with chemotherapy only: 85,2% and 94,3% (I type) and 77,7% and 85,6% (II type). In the multivariant analysis only one factor was defined as statistically significant - the number of the patients randomized by the participating centers. OS and DFS were much higher in the centers randomized 6 and more patients comparing with less than 6 patients: 82,9%and 90,7% vs 48,8% and 63%, respectively (0,003). 1. So we can suggest that maintenance with ATRA alternating with chemotherapy is less effective than chemotherapy only. Whether addition not substitution of ATRA to chemotherapy maintenance will change the results will be checked in the next study.2. The experince of the centers in APL treatment is a cruicial point for survival.

Myelodysplastic syndrome (MDS) represents a heterogenous group of myeloid neoplasms characterized by abnormal differentiation and maturation of myeloid cells, bone marrow failure and genetic instability. The recent clinical and laboratory investigations suggest that MDS is closely related to diseases in which the bone marrow failure is mediated at least in part by the immune system. The are few studies concerning the of efficacy of treatment of MDS pts with cyclosporine A (CSA) but they are limited to the group of pts with bone marrow hypoplasia. The aim of our study was to evaluate the efficacy of CSA treatment in MDS pts as first line or second line therapy. 48 pts with different forms of MDS were included in study. The group of first line CSA treatment included 30 pts, male-18/female-12, RA-3, RARS-1, RCMD-18, RAEB-7, RAEBt-1, 20-normal karyotype, 10-different abberations including: 5q−, 16q+, −7, 12q+, −Y, [11p+,7q−] and complex abb. Hypoplastic bone marrow was revealed in 15 pts, hyperplastic-8 pts, hypo/hyper-7 pts. Second line therapy group included 18 pts, male-9/female-9, RCMD-11, RARS-1, RAEB-5, RAEBt-1, normal karyotype-3, cytogenetic anomalies-13 (+8, 5q−,−7, +8 and complex abb.). Hypoplastic bone marrow was revealed in 12 pts, hyperplastic-4 pts, hypo/hyper-4 pts. The first line therapy consited of splenectomy in 8 pts, low doses of Ara-C-3, interferon-α-3, chemotherapy-2 and ATG-2 pts. CSA was applied at 5–10 mg/kg/day initially and then adjusted according to blood levels and toxicity. The maintenance dose was 1–3 mg/kg/day. Minimum time to response evaluation was one month. Complete response (CR) was defined as normal PB counts, BM aspirate; partial response-improvement of PB counts to 50% of normal and freedom from transfusions; stabilization-decrease of transfusion requirements and stabilization of PB counts for more then 1 month. Total response rate in first group was 60% (18 pts) with median follow up of 10 months (2–134). CR was estimated in 20% (6pts), median follow-up 72 months (44–134). 2 pts with CR are in clonal remission. 2 pts from response group developed acute leukemia (AL). 40% of pts showed no response.58% of pts without response developed RAEB or AL. 42% of pts were in stable disease and were treated with another modalities. The response rate in second group was 61% (11 pts) with median follow-up of 7 months (1–78). 22% (4 pts) achieved CR, median follow-up 60 months (43–78). 39% of pts showed no response. 71% from these pts (5) transformed to RAEB or AL. 2 pts remained in stable disease. In both groups response was registrated from 1 to 4 months from treatment initiation (median 3 months). CR was achieved in the majority of pts after 1 year of treatment. Response was achieved in 77% of pts with hypo/hyper and hypoplastic bone marrow and in 12% of pts with hyperplastic bone marrow. Overall survival was decreased in pts with more the 5% blasts in bone marrow (p=0,02 for 1st line group, p=0,075 for 2nd line group), and increased for pts with hypo and hypo/hyper bone marrow cellularity (p=0,002 for 1st line group). There was no impact of cytogenetics. We may conclude, that CSA demonstrates good efficacy in therapy of MDS pts, especially for pts with RA, RARS and RCMD with hypo and hypo/hypercellular bone marrow and reactive lymphoid nodules in bone marrow. It can be initiated as 1st or 2nd line therapy and should be continued at least for 3 months before evaluating of response.

Nearly all de novo APL patients (pts) undergo complete remission (CR) when treated with all- trans-retinoid acid (ATRA) plus chemotherapy. Nevertheless a significant portion (20%) of these pts ultimately relapse during the first 2 years of therapy. Minimal residual disease (MRD) monitoring using RT-PCR is widely recognized method for detection of molecular relapses (MR) in APL pts during hematological remission. However, the precise MR definition and significance of therapy changing when MR is detected are still controversial. We report the results of molecular monitoring and MR treatment in 40 pts (17 male, 23 female, median age = 33) who were included in the APL studies from 1997 to 2005. The induction and consolidation consisted of four 7+3+ATRA courses or four courses of 5 days Daunozome + ATRA or AIDA-protocol. Maintenance (MT) was performed for 2 years of CR with chemotherapy (5+2 courses) or chemotherapy combined with ATRA or monotherapy with ATRA+INF-alfa after Daunozome. RT-PCR for PML/RARα was performed on fresh marrow aspirates in all pts before treatment and periodically (2–3month) during 2 years after CR induction (2–18 investigations, median 6, for each pt). RT-PCR was performed using recommendations of BIOMED-1 Concerted Action (1999). MR was defined as probable if chimeric transcript was detected once and was not find out by second investigation and as proved when PML/RARA was detected at least twice by consecutive investigations (in 2–4 weeks). In case of proved MR we changed the type of MT. In pts with early MR ( 12 mo of CR) were treated with ATRA+IFN-α. After two hematological relapses (HR) in the group of probable MR we started to change the type of MT even if MRD was detected once. The Table 1 reflects the effect of MT changes on the frequency of HR in pts with MRs. Table 1 Maintenance Probable MR Proved MR No MR/relapsed MT changed /pts relapsed MT unchanged/pts relapsed MT changed/pts relapsed MT unchanged /pts relapsed Chemotherapy (n=19) 3/0 2/1 3/0 1/1 10/1 Chemo+ATRA (n=15) - 6/1 1/0 - 8/1 ATRA+IFN- α (n =6) 1/0 1/1 1/0 - 3/2 Total (n=40) 13/3 6/1 21/4 Our data shows the equal frequency of HR in pts with and without MR: 4/19 and 4/21. The absence of difference is probably due to the treatment changes in case of MR. We also can admit that ATRA monotherapy as maintenance is ineffective approach (3 MR and 3 HR). We revealed the statistically significant difference in the probability of hetmatological relapse in pts with MR in whom MT was changed (0 from 9 relapsed) and not changed (4 from 10 relapsed) (p= 0,04). So it seems reasonable that in proved and probable MRs MT should be changed. However, more investigations should be done for definition of the best postremission treatment strategy in APL pts with MRD.

Background: MCL is B-cell neoplasm diagnosed predominantly among older men. (R)CHOP-like regimens demonstrated high response rate, but the event-free survival (EFS) and overall survival (OS) are disappointingly short - 16-20 months and 3-4 years, respectively. An addition of high-dose AraC (12 g/m2) to the upfront therapy and autoSCT have significantly improved outcomes but remain feasible largely for younger and medically fit patients. Based on the activity and good tolerance of gemcitabine-oxaliplatin combinations in relapsed and refractory MCL patients, we developed an alternative first-line regimen for patients who are not candidates for R-HD-MTX-AraC (R-HMA). We presented an initial data of our pilot protocol at ASH 2012 (#2043). According to the protocol patients who had renal insufficiency and/or experience prohibitive toxicity following the first course of R-EPOCH, were assigned to receive R-EPOCH/R-GIDIOX regimen, while others were treated with R-EPOCH/R-HMA regimen. Both arms received consolidative autoSCT followed by R-maintenance. Aim: Assess toxicity and efficacy of R-DA-EPOCH/R-HMA and R-DA-EPOCH/R-GIDIOX in untreated MCL patients eligible for autoSCT. Patients and Methods: 47 untreated MCL patients from 6 centers were enrolled in prospective study between May 2008 - Sep. 2013; stage II-IV; ECOG 0-3; median age 55 years (29-64); M/F 76%/24%; MIPIb: 28% low, 33% intermediate and 39% high risk. Following 1st R-EPOCH patients were assigned to receive either R-DA-EPOCH/R-HMA or R-DA-EPOCH/R-GIDIOX regimen. In the absence of hematological toxicity gr. 4, severe infections and renal failure patients received R-HMA (R 375 mg/m2 d1, MTX 1000 mg/m2/24 hours d 2, AraC 3000 mg/m2 q 12 hrs d 3-4). Patients who experienced at least one of the complications above received R-GIDIOX (R 375 mg/m2 d 1, gemcitabine 800 mg/m2 d 2 and 5, oxaliplatin 120 mg/m2 d 3, irinotecan 100 mg/m2 d 4, dexamethasone 10 mg/m2 IV d 2-6, ifosfamide 1000 mg/m2 d 2-6). Subsequently these courses were alternating with R-DA-EPOCH in each arm of the protocol. Patients who achieved CR after the first cycle (2 courses), received additional 2 cycles, (for a total 6 courses). Patients without CR after 2 cycles of therapy received 2 more cycles, for total of 8 courses, unless they progressed on therapy. Those patients who achieved PR/CR/CRu underwent autoSCT (BEAM-R). Response the therapy was assessed by Cheson's criteria (2007). Patients with residual PET+ tumor after autoSCT were consolidated with local radiotherapy. Post-transplant R- maintenance was administered for 3 years (R-375 mg/m2 every 3 months). Patients were analyzed on an intent-to-treat basis. Results: 29/47 patients were treated on R-HMA arm (Arm1) (median 51years; MIPIb: 35,7% low, 28,6% intermediate and 35,7% high risk) and 18/47 patients were on R-GIDIOX arm (Arm2) (median 60 years; MIPIb: 16,7% low, 38,9% intermediate and 44,4% high risk). There was 1/29 induction death after first R-HMA course (acute renal failure and septic shock). 1 of 18 patients had disease progression before autoSCT in Arm2. 28/29 patients from Arm1 achieved CR/CRu (96,6%). In Arm 2 OR and CR/CRu rates were 94,4% (17/18) and 77,8% (14/18), respectively. Main non-hematological toxicity of R-GIDIOX was asymptomatic elevation of transaminases (gr. 1-2 and 3-4 in 65,5% and 6,9% of courses respectively), while leukopenia gr. 4 occurred in 74,1% of courses (median 5 days, range 1-13), thrombocytopenia gr. 4 -39,7% courses. 45/47 patients underwent autoSCT: 28/29 in Arm1 and 17/18 in Arm2. The sources of stem cells were PBSC in 39/45 patients (86,7%) and BM in 6/45 (13,3%) patients with PBSC collection failure following R-HMA (3/28) or R-GIDIOX (3/17). With median follow-up of 31 months (range 11-76), the estimated 4-year OS and EFS remain identical in both groups: 78% (SE 12%) and 72% (SE 18%), respectively. Conclusions: Combination of R-DA-EPOCH/R-GIDIOX followed autoSCT and R-maintenance is well tolerated and produces EFS/OS similar to those seen with more toxic regimen utilizing R-HD-MTX-AraC. Equal outcomes were observed despite higher proportion of high risk patients treated with non-HD-AraC regimen. We conclude that R-GIDIOX can be an alternative component of induction regimen for those patient with MCL who are not candidates for intensification with high-dose AraC and MTX. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Background: The greatest progress in treatment of lymphoproliferative malignancy multiple myeloma (MM) was achieved in the past decade. According to population studies, in the last decade 5-year overall survival (OS) rate in patients (pts) with MM in the Germany was 39%, in the USA - 47%. Aims: To evaluate 5-year OS and progression-free survival (PFS) rates, to reveal the main independent predictor of mortality in pts with MM in Russia. Patients and Methods: Five medical centers participated in prospective study in Russian Federation. During the period from January 1st, 2009 to January 1st, 2012 170 pts with newly diagnosed MM were included (68 male, 102 female) in the study. The median age was 61 years (range 42 - 86). The primary endpoint was January 1st, 2015. 111 of pts (65%) were younger 65 years. At the moment of diagnosis most pts (25%) were in age between 55 and 60 years. The largest incidence rate for both sexes was in age between 60 and 65 years (Figure 1). Distribution of disease stages according to the Durie Salmon system was the following: III stage - 50%, II stage - 45%, I stage - only 5%. The most pts (55%) were with myeloma G. 83% of pts received bortezomib-based first line treatment, 16% of pts received only chemotherapeutic drugs; refusal of treatment was registered in 1% of cases. Autologous transplantation was performed in 14 (13%) patients in the age under 65 years. Overall response was achieved in 68% of pts, complete remission - in 26%. OS and PFS were evaluated using Kaplan-Meier analysis. Time to OS and PFS (events: progression or death) were measured from the initiation of treatment. Multivariate Cox proportional hazards regression analysis (after univariate analysis) was used to identify the main independent predictor of death. Statistical analysis was performed with SAS v.9.1. Results: 5-year OS rate was 37%, 5-year PFS - 16%, the median follow-up was 38 months (Figure 2 and 3). According to multivariate analysis the main factor associated with mortality was the stage of disease. For the I stage 5-year OS was 100%, for the II stage - 36%, for the III stage - 25% (the pairwise differences between OS was statistically significant, ð Conclusion: Our study revealed that the median age in a study pts with MM is ten years less than in Europe and USA. Main independent predictor of OS rate is the stage of disease. Figure 1. Multiple myeloma crude incidence rates (x 100,000) by age class and gender based on five regions of Russia. Figure 1. Multiple myeloma crude incidence rates (x 100,000) by age class and gender based on five regions of Russia. Figure 2. OS and PFS (without resistant cases) in pts with multiple myeloma. Figure 2. OS and PFS (without resistant cases) in pts with multiple myeloma. Figure 3. OS and PFS (without resistant cases) in pts with multiple myeloma. Figure 3. OS and PFS (without resistant cases) in pts with multiple myeloma. Disclosures Volodicheva: CELLTRION, Inc.: Research Funding.

Background: Necessity of maintenance therapy (MT) in patients with multiple myeloma (MM) after auto-HSCT continues to be a matter of debate in the community. To ensure it's proper application, it is important to set clear criteria when it is an appropriate type of treatment. MRD status of the patient after auto-HSCT could be such a criteria, than can be used to stratify the risk of relapse and justify the MT. Aims: To assess the efficacy of MT in patients with MM achieving a complete response after auto-HSCT accounting on whether or not they have minimal residual disease. Patients and Methods: Fifty-two patients with MM (19 male and 33 female, 24 to 66 years old - median, 54 years) who had achieved a complete response after auto-HSCT were enrolled in a prospective randomized clinical study in the period from January 2014 to February 2016. Subjects were at the following stages of the disease (ISS): 11 at Stage I, 23 at Stage II, and 18 at Stage III. The remission induction protocol included: bortezomib-containing regimens (VCD, PAD) for all 52 patients, immunomodulatory agents for 8, and bendamustine for 2. Distribution of patients by type of anti-tumor responses (according to the International Myeloma Working Group classification criteria) after induction was as follows: complete response in 26 patients (50 %), very good partial response in 12 subjects (23 %), and partial response in 5 individuals (27 %). Single auto-HSCT was used in 36 subjects and tandem auto-HSCT in 16. At 100 days post auto-HSCT, the MRD status was assessed by means of bone marrow examination using six-color Flow Cytometry with a panel of antibodies to the following antigens: CD38, CD138, CD45, CD56, CD117, and CD19. Tests yielding less than 50 clonal plasma cells in 500,000 white blood cells (< 0.01 %, Limit of Detection: 10-4) were reported as an MRD-negative status. A stringent complete response after auto-HSCT had been achieved in 25 patients (48 %), while an MRD-positive status was detected in 27 subjects (52 %). At 100 days post auto-HSCT, MRD-negative patients were randomized into two arms: 14 subjects were given bortezomib MT (1.3 mg/m2 s.c., one dose every two weeks for one year), and 11 patients were not administered M"; one female patient was subsequently withdrawn from maintenance therapy due to drug toxicity. Some of the MRD-positive subjects (19) received bortezomib MT according to the aforementioned regimen, while the others (8 patients) did not receive MT. The follow-up period from the time of MRD detection ranged from 5 months to 27 months (median 14 months). Two deaths (unrelated to the underlying condition) were registered in the course of the trial. Relapse-free survival (RFS) rate was selected as the efficacy endpoint for MM patients. Survival curves were constructed using the Kaplan-Meier method and a log-rank test was used to compare the survival estimates between two groups. The compared groups were overall balanced for known prognostic factors. Statistical analysis was done using SAS 9.4. Results: MRD-positive patients were found to have a lower 2-year RFS rate compared with MRD-negative patients: 49 % vs 60 % (P=0.056); the presence of MRD increases the risk of relapse (Hazard Ratio: 1.7, 95 % CI: 1.3 − 3.4) (Fig. 1). MT administered in MRD-negative patients did not increase their RFS: the 2-year RFS rates were found to be approximately the same in the MT and no MT arms (P=0.46), and equal to 84 % (Fig. 2). MT used in MRD-positive patients did increase their RFS: the 2-year RFS rate was higher in patients treated with MT compared with the no MT treated: 43 % vs 35 % (P=0.076) (Fig. 3). Following completion of MT, 8 out of 19 MRD-positive patients (42 %) achieved a better antitumour response, i. e. a stringent complete response. Conclusion: The reported study demonstrated that assessment of the MRD status provides an effective criterion for risk stratification in patients who have received auto-HSCT and are considered for MT. Maintenance therapy appears to be most appropriate in patients found to be MRD-positive after auto-HSCT, while for MRD-negative patients carrying out MT is inappropriate because it does not result in significant effect, but is associated with toxic complications. This study was approved by the local ethics committee. Disclosures No relevant conflicts of interest to declare.

Background: According to current data B-cell lymphoma unclassified (BCLU), intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma represents a highly aggressive type of lymphoma with dramatically bad response for chemotherapy. Cases with translocation of two genes (MYC and BCL2 or BCL6) are divided into double-hit lymphomas (DHL). We need to estimate risk factors to intensify treatment and manage indications for autologous stem cell transplantation (auto-SCT) according to individual characteristics. Aim: To evaluate results of BCLU treatment according to LB-M-04±R protocol in adults younger than 60 years old and CHOP-like regimens in elderly patients (≥60 years old) with auto-SCT in high risk patients group. Patients and Methods: 21 pts observed in National Research Center for Hematology (Moscow) between 2004 and 2014 years were included in a current study. All of them were convenient to BCLU diagnosis criteria according to WHO classification of hematological malignancies (2008). Genetic analysis included: standard karyotyping in 7 pts (6 – lymph nodes samples, 1 sample of cerebrospinal fluid). FISH analysis was performed in 21 pts (in 7 cases on tumor cells; on imprints of tumor in 4 cases, on histologic slides from paraffin blocks - in 10 cases). Taking into account heterogeneity of a common group we divided all pts into 2 subgroups: DHL and non-DHL cases (7 vs. 14 respectively). Pts younger than 60 years old (17 pts) were treated according to LB-M-04±R protocol which included A-C-A-C courses. Course A consisted from dexamethasone 10 mg/m2 i.v. 1-5 ds, methotrexate 1500 mg/m2 12-hours infusion 1st d, ifosfamide 800 mg/m2 1-5 ds, vincristine 1 mg/m2 1st d, doxorubicine 50 mg/m2 3rd d, cytarabine 150 mg/m2 4-5 ds, etoposide 100 mg/m2 4-5 ds; course C included dexamethasone 10 mg/m2 i.v. 1-5 ds, methotrexate 1500 mg/m2 12-hours infusion 1st d, vinblastine 5 mg/m2 1st d, cytarabine 2000 mg/m2 twice a day 2-3 ds, etoposide 150 mg/m2 3-5 ds. Rituximab were indicated before chemotherapy in dosage 375 mg/m2. CNS prophylaxis was made by intrathecal administration of prednisolone 30 mg, cytarabine 30 mg, methotrexate 15 mg in 1st day of each course. When complete remission (CR) was achieved after 2 courses, treatment lasted 4 courses. When tumor regression was diagnosed after 4 courses, treatment continued till 6 courses. 4 pts ˃60 years were managed by CHOP-like regimens ±R. We performed auto-SCT in non-DHL group with signs of poor prognosis (bone marrow involvement, multiple extranodal sites, CR after 6 courses) and in DHL when CR had been achieved after 4 courses. Pts with DHL after auto-SCT received 2 R-EPOCH courses more. As a conditional regimen BEAM was used. An overall survival (OS) as a primary endpoint and event-free survival (EFS) were assessed with using the Kaplan-Meier method (with log-rank test) to estimate an efficacy of treatment. Statistical analysis was performed with SAS 9.3 (SAS Institute Inc. Cary, NC). Results: Studying group included 9 males and 12 females. Comparing pts according DH and non-DH status, DHL group (n=7) consisted of 2 males and 5 females, median age 48 years (30-74), ECOG status was 2.6 (95%CI 1.3-3.9) and non-DH group consisted of 7 male and 7 female, median age was 46 (23-76), ECOG status was 2.4 (95%CI 1.8-3.1). DHL pts had stage II of lymphoma according to Ann-Arbor classification in 1 case, III in 1 case, IV in 5 cases. Non-DHL pts had stage II of lymphoma in 2 cases and IV in 12 cases. Bone marrow involvement was revealed in 2 cases in DHL group and in 5 cases in non-DHL group. More than 1 extranodal site took place in 3 cases of DHL and 8 cases of non-DHL. Survival rates of groups were comparable because they were not significantly different of these characteristics. The 2-year OS and EFS rates were less for DHL pts compared with non-DHL pts: OS: 43 vs. 75%, P=0.24 and EFS: 29 vs. 66%, P=0.09 respectively (Figures 1and 2). Auto-SCT was performed in 2 pts with DHL treated by LB-M-04±R protocol (both pts still be alive) and in 3 pts with non-DHL (1 pt treated by LB-M-04±R and 1 treated by CHOP-like regimen+R are alive in CR and 1 pt treated by LB-M-04±R protocol developed a relapse). Conclusions: Low OS and EFS in BCLU group are caused particularly by DHL cases. We need to enlarge an observation group to confirm benefits of auto-SCT in BCLU pts with signs of poor prognosis. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.