Background: Primary bone lymphoma (PBL) accounts for about 5% of extranodal lymphomas, the most common type are Diffuse Large B-cell Lymphoma (PBL-DLBCL). R-CHOP chemotherapy combined with or no radiation therapy can induce 5-year overall and progression free survival about 63% and 60% for localized-stage and only 41% and 35% for advanced stage and with adverse factors (AF). Due to the rarity of the disease the optimal treatment strategy still remains unknown. Further research is thus needed to increase treatment efficacy for patients with advanced stage PBL-DLBCL and with AF. Aims: To evaluate the efficacy of mNHL-BFM-90 program in adult patients with advanced stage PBL-DLBCL and with AF. Methods: Twenty three previously untreated pts with PBL-DLBCL underwent mNHL-BFM-90 treatment between May 2007 and July 2014; mean age 41 years (range 17-65); age ≥60 years 3 pts (13,6%); M\F=14\9. Tumor stage according to the Ann-Arbor classification: stage I (involvement of 1 bone) - 7 pts (30,4%), II (involvement of regional lymph nodes) - 3 pts (13%), IV (multiple bone involvement) - 13 pts (56,6%); stage >I 16 pts (69,5%). All pts with stage I had large-size tumors (>6sm) with soft tissue contact invasion. LDH elevation was observed in 10 pts (43,5%), B-symptoms in 15 pts (65%), large-size tumors - 20 pts (87%). The most common tumor sites were the skull bones, vertebrae, and femur. All patients received treatment according to the mNHL-BFM-90 intensive program This program was modified in the following way: adriamycin was administered on the 3rd day of course AA at a dose 50 mg/m2; methotrexate was administered on the 1st day of course C at a dose 1.0 g/m2 for 12 hours. All patients underwent from 4 to 6 courses. Twelve (52%) pts received rituximab on day 0 prior to each course of therapy. Five pts received radiotherapy, all pts received intrathecal prophylaxis of central nervous system (CNS) involvement. Results. Complete remissions were achieved in 23 pts (100%). Relapses were observed in three patients in 6, 9 and 40 months after completion of treatment. From 2 pts with early relapse, one was diagnosed as «double-expression lymphoma» (MYC expression >70%, BCL2 >60%), both pts proliferation index Ki-67 accounted 100%. All 3 pts received salvage therapy and died from progression of disease. With a median follow-up of 69 months (range 17-110) both progression-free and overall survival of 23 pts constituted 87%. Grades 3, 4 hematological toxicity was observed in all pts. No deaths related to mNHL-BFM-90 treatment occurred. No second malignancies were observed. Conclusion The mNHL-BFM-90 demonstrated high efficacy and acceptable toxicity in patients with advanced-stage PBL-DLBCL and with AF. Figure Figure. Disclosures No relevant conflicts of interest to declare.

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Background. Aggressive lymphomas accounts for about 80% of primary gastrointestinal non-Hodgkin`s lymphomas (PGIAL). In adults the most common type is diffuse large B-cell lymphoma (DLBCL). Burkitt lymphoma (BL) is rare and mainly affects children. R-CHOP chemotherapy can induce favorable result for localized-stage. But the presence of adverse factors (AF) and advanced stage decrease the efficacy of this therapy: 3-year progression-free survival (PFS) and overall survival (OS) are about 50% and 60% respectively. The optimal treatment strategy for this pts still remains unknown. Aim. Efficacy and safety assessment of the modified chemotherapy protocol NHL-BFM-90 (m NHL-BFM-90 and LB-M-04) in the treatment of the PGIAL with advanced stage and AF. Patients. 74 previously untreated pts with PGIAL underwent mNHL-BFM-90 or LB-M-04 treatment between January 2002 and December 2015; out of them, 45 pts - primary gastric lymphoma (PGL), 29 pts - primary intestinal lymphoma (PIL); median age 39 years (range 14-72); age ≥60 years 10 pts (13,5%); M\F=44\30; stage >I 58 pts (78,3%); B-symptoms 30 pts (40,5%); Bulky disease 28 pts (37,8%). Patients characteristics in groups presented in Table 1. In the PIL group compared with the PGL was predominance of male (M\F=20\9 versus 21\24), stage II-IV (89,6% versus 71%), high level of LDH (72% versus 49%), Bulky disease (55% versus 27%). In pts with high Ki-67 (>40%) FISH test on t(8;14) was performed. Burkitt`s lymphoma diagnosed in 5 pts (11%) with PGL and 9 pts (31%) with PIL. In the PIL group more than half (58,6%) pts received surgical treatment before chemotherapy, and only 2 pts (4,4%) - in the PGL group. Of the 74 pts, 60 (81%) were diagnosed with DLBCL, 14 (19%) - BL. All pts with DLBCL received treatment according to the mNHL-BFM-90 program (2 courses A and 2 courses B) that was modified in the following way: doxorubicin (50mg\m2) was added on the third day of course A. All patients with BL received treatment according to the LB-M-04 program (2 courses A and 2 courses C) that was modified in the following way: doxorubicin (50mg\m2) was added on the third day of course A, methotrexate was administered on the 1st day of course C at a dose 1500mg/m2 for 12 hours. No one received consolidation radiotherapy from both groups. Results. In DLBCL group the overall response rate (ORR) was 95%. Complete remission (CR) was achieved in 38 from 40 pts (95%) in PGL, and 17 from 20 pts (85%) PIL. With a median follow-up of 74 months (range, 1-156) disease-free and overall survival of 60 pts with DLBCL constituted 86.7% and 91,7%, respectively. In BL group all pts achieved CR and alive with no signs of progression with a median follow-up of 110 months (range, 62-154). Hematologic toxicity of grade 3 and 4 was observed in 80% of pts. Severe complications became the reason for subsequent switch to CHOP therapy after 2 courses in 6 pts with PGL DLBCL. There was no treatment-related mortality. Conclusions. The mNHL-BFM-90 and LB-M-04 demonstrated acceptable toxicity and high efficacy in patients with PGIAL. Burkett lymphoma is not rare in adults with PGIAL and detection of t(8;14) can improve treatment outcomes. Table 1 Characteristics of the patients with aggressive primary gastrointestinal non-Hodgkin`s lymphomas. Table 1. Characteristics of the patients with aggressive primary gastrointestinal non-Hodgkin`s lymphomas. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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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.