The efficacy and the safety of the administration of multipotent mesenchymal stromal cells (MMSCs) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic hematopoietic cell transplantation (HSCT) were studied. This prospective clinical trial was based on the random patient allocation to the following two groups receiving (1) standard GVHD prophylaxis and (2) standard GVHD prophylaxis combined with MMSCs infusion. Bone marrow MMSCs from hematopoietic stem cell donors were cultured and administered to the recipients at doses of 0.9–1.3 × 106/kg when the blood counts indicated recovery. aGVHD of stage II–IV developed in 38.9% and 5.3% of patients in group 1 and group 2, respectively, (P = 0.002). There were no differences in the graft rejection rates, chronic GVHD development, or infectious complications. Overall mortality was 16.7% for patients in group 1 and 5.3% for patients in group 2. The efficacy and the safety of MMSC administration for aGVHD prophylaxis were demonstrated in this study.

Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the regulatory molecular mechanisms of the disease, we performed RNA sequencing analysis of 14 pairs of skin samples collected from patients with psoriasis. Subsequent pathway analysis and extraction of the transcriptional regulators governing psoriasis-associated pathways was executed using a combination of the MetaCore Interactome enrichment tool and the cisExpress algorithm, followed by comparison to a set of previously described psoriasis response elements. A comparative approach allowed us to identify 42 core transcriptional regulators of the disease associated with inflammation (NFκB, IRF9, JUN, FOS, SRF), the activity of T cells in psoriatic lesions (STAT6, FOXP3, NFATC2, GATA3, TCF7, RUNX1), the hyperproliferation and migration of keratinocytes (JUN, FOS, NFIB, TFAP2A, TFAP2C) and lipid metabolism (TFAP2, RARA, VDR). In addition to the core regulators, we identified 38 transcription factors previously not associated with the disease that can clarify the pathogenesis of psoriasis. To illustrate these findings, we analyzed the regulatory role of one of the identified transcription factors (TFs), FOXA1. Using ChIP-seq and RNA-seq data, we concluded that the atypical expression of the FOXA1 TF is an important player in the disease as it inhibits the maturation of naive T cells into the (CD4+FOXA1+CD47+CD69+PD-L1(hi)FOXP3−) regulatory T cell subpopulation, therefore contributing to the development of psoriatic skin lesions.

A lower chemotherapeutic load and a small number of allogeneic BMTs did not affect total positive treatment results in adult patients with ALL, by complying with the principle achieving the continuity of cytostatic effects and by preserving the total cytostatic loading dose. The results of the Russian investigation casts some doubt on the necessity of using very intensive consolidation cycles and performing a large number of allogeneic BMTs in adult patients with ALL.

Аmp1q21 is one of the most common chromosomal abnormalities in patients with new-onset MM and may appear in the course of disease progression. The presence of аmp1q21 is an important prognostic factor and must have to be included in the diagnostic study both at disease onset and progression.

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 BII-III, T-III; LDH < 2N; no late CR; t(4;11)-negative), 59,2% (n=148) - in the high risk (HR) 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.