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<b><i>Introduction:</i></b> This prospective study evaluated a calcineurin inhibitor-free graft-versus-host disease (GVHD) prophylaxis regimen of ruxolitinib in combination with post-transplant cyclophosphamide (PTCy). <b><i>Patents and Methods:</i></b> Twenty patients with primary or secondary myelofibrosis were prospectively enrolled. Reduced intensity conditioning was performed, followed by allogeneic stem cell transplantation from related (<i>n</i> = 7) or unrelated (<i>n</i> = 13) donors. GVHD prophylaxis included only PTCy and ruxolitinib (45 mg) from day–7 to day–2, and 15 mg from day+5 to day+100. This trial was registered at www.clinicaltrials.gov as #NCT02806375. <b><i>Results:</i></b> Primary engraftment was documented in 17 patients. One patient experienced primary graft failure and 2 died before engraftment. Eleven patients demonstrated severe poor graft function (SPGF), which required ruxolitinib dose reduction. The regimen was well tolerated, with grade 3–4 non-haematological toxicity in 30%, viral reactivation in 45%, and severe sepsis in 15% of patients. The incidence of acute GVHD grade II–IV was 25%, grade III-IV GVHD was 15%, and moderate chronic GVHD was 20%, with no severe cases. Only 2 patients required systemic steroids. Haematological relapse was documented in 1 patient. Two-year non-relapse mortality was 15%, 2-year overall survival was 85%, and 2-year event-free survival was 72%. <b><i>Conclusion:</i></b> GVHD prophylaxis with PTCy and ruxolitinib is associated with low toxicity, good acute and chronic GVHD control, and low relapse incidence. However, the relatively high rate of SPGF should be taken into account. SPGF could possibly be mitigated by ruxolitinib dose reduction.

The addition of rituximab to a variety of chemotherapy regimens for the treatment of patients with CLL has yielded promising results in phase II trials. The R-FC regimen demonstrated particularly high rates of overall response (ORR), complete remission (CR), progression-free survival (PFS) and overall survival (OS) in relapsed/refractory CLL (Wierda, et al, JCO 2005). REACH was an open-label, multicenter, randomized, phase III study to evaluate the efficacy and tolerability of R-FC versus FC in relapsed or refractory patients with CD20 positive CLL. The primary endpoint of the study was progression free survival. Five hundred and fifty two patients from 17 countries were randomized (1:1) to receive either R-FC or FC. Rituximab was administered IV before the FC infusion for a total of 6 treatment cycles at intervals of 28 days (Cycle 1: 375 mg/m2 IV; Cycles 2–6: 500 mg/m2 IV). Fludarabine (25 mg/m2 IV/day) and cyclophosphamide (250 mg/m2 IV/day) were administered over 3 days for 6 cycles. Baseline demographics, disease characteristics, and prognostic factors were well balanced between the two arms. Median age was 63 years. All Binet stages were represented (A 10%, B 59%, C 31%). A median of one prior treatment had been administered, consisting of single-agent alkylator therapy (66%), purine-analogs (16%), or combination treatments (CHOP, COP, F-containing, 18%). Patients with prior FC combination treatment or prior rituximab were not eligible. Median observation time was 25 months. The primary endpoint PFS was significantly prolonged by median 10 months in the R-FC arm (30.6 months) compared to FC (20.6 months, p =0.0002, Hazard Ratio (HR) 0.65 [95% CI 0.51; 0.82]). Secondary endpoints EFS, TTNT, DR showed similar results. ORR were higher for R-FC vs. FC (70% vs. 58%, p=0.0034), due to superior CR rates (24% vs. 13%, p=0.0007). Multiple subgroups were analyzed applying a Cox-regression model: all Binet stages experienced similar incremental benefits in PFS (HR Binet A 0.75, B 0.65, C 0.61). Mutational status and cytogenetic subgroups remained prognostic and benefited from the addition of rituximab to FC (HR IgVH unmutated 0.62, mutated 0.7; del17p pos 0.75, neg 0.63; del13q pos 0.56, neg 0.77). Median overall survival was not reached for R-FC and was 53 months for FC, (p=0.29, HR 0.83). Of 47 patients that relapsed and were treated in the R-FC arm, 30% received rituximab again. Sixty-nine patients were treated at relapse in the FC arm, and 49% received rituximab. Grade 3/4 Adverse Events were higher in the R-FC arm (80%) vs. FC (74%), but serious adverse events were similar (50% vs. 48%, respectively). Grade 3/4 neutropenia and febrile neutropenia were only marginally increased for R-FC (42% and 15%) vs. FC (40% and 12%, respectively), the same was seen for thrombocytopenia (R-FC 11% vs. FC 9%). Grade 3/4 infections (R-FC 18%, FC 19%) were similar, and there was no difference in bacterial, viral, or fungal infections between the two arms. Grade 3/4 anemia was slightly increased in the FC arm (R-FC 2%, FC 5%). Slightly higher Fatal Adverse Events were seen with R-FC (13%) vs. FC (10%). Fatal SAEs were mainly due to infections, secondary neoplasms, and cardiac disorders. Summary and conclusion: In this large randomized trial in relapsed or refractory CLL, with 10 months improvement in PFS and a doubling of CR rates, R-FC was statistically significant and clinically meaningful superior to FC in the primary analysis. Improvement in PFS was seen across most subgroups, including all Binet stages. Fatal AEs were relatively high in both arms. However, overall, the addition of rituximab to FC in REACH showed a very favorable risk-benefit profile and did not reveal any new or unexpected safety signals.

In the world, annually the level of emissions from fisheries in the seas reaches 10.8% or 9.1 million tons per year, and according to Russian experts, only in the trawl and snurry fisheries of the Russian Far East, annual emissions are about 1.2 million tons. Therefore, the purpose of this work is to analyze the structure of catches of the main commercial species of crabs and by-catch of other invertebrates and fish. The collection of biological materials and fishing statistics was carried out in the course of research work from July 27 to October 5, 2021 on the research vessel (RV) Zodiak in the northern part of the Sea of Okhotsk (North Sea of Okhotsk subzone SOM, 55°01ʹ58 °05ʹ N and 142°00ʹ-154°02ʹ E; West Kamchatka subzone ZK, 58°00ʹ-59°40ʹ N and 154°45ʹ-159°30ʹ E). In the SOM, studies have shown that, depending on the depth, the near-bottom temperature varied widely from –1.48 to 2.84 °С, in the WK — from 0.20 to 6.72 °С, which is generally typical for this season of the year and water areas. The number and distribution of the main objects of the crab fishery, namely the opilio snow crab in the SOM and the blue crab in the ZK, are at the average long-term level. A rare extensive research area made it possible to describe the true distribution of crabs. The structure of hydrobiont catches also included 13 trumpeter species and 13 fish species in two subzones of the Sea of Okhotsk. Since crab fishing in different periods of the year is carried out in different water areas and is mainly concentrated in a small area, structure of catches is likely will be less diverse.

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