Clinical efficacy of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has been demonstrated in haploidentical and HLA-matched bone marrow but not in unrelated peripheral blood stem cell (PBSC) transplantations. Also, no direct comparisons have been published with current standard of care, combination of antithymocyte globulin (ATG), calcineurin inhibitors, and either methotrexate or mycophenolate mofetil (MMF). Eighty-six adult patients (median age 34 years; range, 18 to 59) with acute myeloblastic and lymphoblastic leukemia underwent unrelated PBSC transplantation with PTCy, tacrolimus, and MMF as GVHD prophylaxis in the single-center trial (clinicaltrial.govNCT02294552). The control group comprised 125 consecutive historical control patients who received ATG, tacrolimus, and methotrexate or MMF. Cumulative incidences of grades II to IV acute (19% versus 45%, P = .0003), grades III to IV acute (4% versus 27%, P < .0001), and chronic GVHD (16% versus 65%, P < .0001) were significantly lower in the PTCy compared with the ATG group. PTCy-based prophylaxis was associated with reduced incidence of nonrelapse mortality (16% versus 36%, P = .005; HR, .55; 95% CI, .34 to .89) and improved overall survival (69% versus 40%, P = .0007; HR, .43; 95% CI, .26 to .70), event-free survival (65% versus 38%, P = .0006; HR, .49; 95% CI, .31 to .78), and GVHD relapse-free survival (52% versus 12%, P < .0001). PTCy-based prophylaxis also had a better safety profile compared with ATG with reduced incidence of veno-occlusive disease, cytomegalovirus reactivation, invasive mycosis, and reduced severity of mucositis. In this study we demonstrated that PTCy in combination with tacrolimus and MMF is a safe and effective GVHD prophylaxis for unrelated PBSC transplantation. Although there are several limitations of the historical control approach, this study suggests the superiority of a PTCy-based approach over an ATG-based prophylaxis.

Mesenchymal stem cells (MSCs) are widely used in cell therapy due to their convenience, multiline differentiation potential, reproducible protocols, and biological properties. The potential of MSCs to impregnate magnetic microcapsules and their possible influence on cell function and ability to response to magnetic field have been explored. Interestingly, the cells suspended in media show much higher ability in internalization of microcapsules, then MSCs adhere into the surface. There is no significant effect of microcapsules on cell toxicity compared with other cell line-capsule internalization reported in literature. Due to internalization of magnetic capsules by the cells, such cell engineering platform is responsive to external magnetic field, which allows to manipulate MSC migration. Magnetically sorted MSCs are capable to differentiation as confirmed by their conversion to adipogenic and osteogenic cells using standard protocols. There is a minor effect of capsule internalization on cell adhesion, though MSCs are still able to form spheroid made by dozen of thousand MSCs. This work demonstrates the potential of use of microcapsule impregnated MSCs to carry internalized micron-sized vesicles and being navigated with external magnetic signaling.

Трансплантация гемопоэтических стволовых клеток (ТГСК) является ведущим методом лечения злокачественных заболеваний системы крови и наследственных заболеваний, а также ряда солидных опухолей у детей, подразделяется на аутологичную (ауто-ТГСК) и аллогенную (алло-ТГСК) трансплантации. Проведение ТГСК осуществляется с учетом показаний, наличия донора-родственного, неродственного, гаплоидентичного, с применением режимов кондиционирования различной интенсивности (миело аблативные, режимы кондиционирования сниженной интенсивности доз, немиелоаблативные), профилактики реакции «трансплантат против хозяина», которая является ведущим осложнением. Наряду с цитостатическим воздействием при выполнении алло-ТГСК осуществляется иммуноадоптивный эффект-«трансплантат против лейкоза».

Whether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy-Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24, p < 0.01; HR 2.65, 95% CI 1.46-4.81, p < 0.01, respectively). Haplo groups experienced a lower leukemia-free survival (LFS) compared to 1Ag-MMUD-PB (Haplo-BM: HR 1.51, 95% CI 1.06-2.14, p = 0.02; Haplo-PB: 1.47, 95% CI 1.05-2.05, p = 0.02); overall survival (OS) was also lower in Haplo-HCT (Haplo-BM: HR 1.50, 95% CI 1.02-2.21, p = 0.04; Haplo-PB: HR 1.51, 95% CI 1.05-2.19, p = 0.03). No differences were observed for graft-versus-host/relapse-free survival (GRFS) and relapse incidence (RI). Haplo-BM was associated with a lower risk of grade III-IV acute graft-versus-host disease (GVHD) (HR 0.44, 95% CI 0.24-0.81; p < 0.01), while no statistical differences were observed between groups for grade II-IV aGVHD and for cGVHD. Use of PTCy in 1Ag-MMUD-HCT is a valid alternative to consider when using alternative donors. Larger analysis of 1Ag-MMUD versus Haplo-HCT are warranted.

Although the prognostic significance of vascular endothelial growth factor (VEGF) has been researched extensively in patients with hematologic malignancies undergoing chemotherapy, its role in allogeneic hematopoietic stem cell transplantation (HSCT) requires further investigation. The present study evaluated the associations between VEGF level and relapse rate and early complications after HSCT. VEGF levels were analyzed in 91 consecutive patients before the start of conditioning, on day 0, on the day of engraftment, and on the day of diagnosis of veno-occlusive disease (VOD). Compared with a normal level, an elevated high VEGF-A level before conditioning was associated with an increased 2-year relapse rate (55% versus 24%, P = .003; hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.49 to 7.08) and decreased event-free survival (20% versus 44%; P = .022; HR, 2.03; 95% CI, 1.11 to 3.72). No association was found between VEGF level and the incidence of acute GVHD (P > .05). In patients with VOD, VEGF-A level was elevated on day 0 and on the day of VOD diagnosis (P < .05). A low VEGF-A level on day 0 was associated with reduced nonrelapse mortality (14% versus 35%; P = .048; HR, 0.32; 95% CI, 0.10 to 0.99). Our results indicate that a high VEGF-A level before HSCT increases the risk of relapse, and a high level after conditioning is associated with increased risks of early complications and nonrelapse mortality.

The aim of this study was to evaluate efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute lymphoblastic leukemia (ALL), and to specify significant factors affecting clinical outcomes. Patients and methods. The study included 354 ALL patients aged 1 to 61 years who underwent allo-HSCT over a period of 1995 to 2015. Before HSCT, 24% of patients were in the 1st remission, 26%-in 2nd remission, 17%, in the ≥ 3rd remission; 34% of patients had active disease. Results. Overall survival (OS) was 47% when HSCT was performed in remission status versus 18% in patients transplanted in active disease state (p <.0001). Appropriate relapse incidence (RI) comprised 26% and 50%, respectively (P <.0001). Five-year OS was similar in children and adults (48% and 47% respectively, p>0.2). Pre-transplant remission state showed certain correlations with OS in pediatric and adult transplant patients, i.e., 79% vs 60% for HSCT in 1st remission; 40% vs 43% in 2nd remission, and 33% vs 23% for the patients treated in ≥ 3rd remission. ALL RI in children and adults were also comparable for HSCT carried out in 1st remission (21% vs 32%), 2nd remission (33% vs 17%), and 17% vs 23% for HSCT performed in ≥3rd remission (p>0.2). Most ALL patients underwent myeloablative conditioning regimen (MAC) before allo-HSCT (n=89). OS in MAC group was 53% versus 40% among patients who underwent reduced-intensity conditioning (RIC) regimens (n=70, p=0.04). The conditioning regimen intensity did not correlate with the RI after allo-HSCT (24% and 30% (MAC vs RIC respectively), p=0.09). Non-relapse mortality (NRM) did not significantly differ for children and adults (32% vs 37%, p>0.2), being dependent on the disease state: 21% vs 25% after HSCT in the 1st remission; 31% and 43%, when treated in the 2nd remission, and 50% vs 61% if transplanted in ≥3rd remission. Conclusion. Allo-HSCT from an HLA-matched related or unrelated donor is indicated in patients with high-risk ALL in first remission and in all the patients in the second remission.

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Background: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Both janus kinase (JAK) inhibitor, baricitinib, and dexamethasone demonstrated the reduction of mortality. In this matched control study we compared dexamethasone to another JAK inhibitor, ruxolitinib. Methods: The study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by 29 clinical and laboratory parameters predicting survival. Results: Ruxolitinib treatment in the general cohort of patients was associated with equivalent to dexamethasone mortality rate: 9,6% (95% CI 4,6-14,6%) vs 13,0% (95% CI 7,5-18,5%, superiority p=0.35, non-inferiority p=0.0137), respectively. Time to discharge without oxygen support requirement was also not different between these groups: 13 vs 11 days (p=0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated reduced mortality in ruxolitnib-treated patients with febrile fever (OR 0.33, 95%CI 0.11-1.00). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p=0.042), ruxolitinib therapy was associated with better safety profile due to reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p=0.025). Conclusions: Ruxolitinib may be an alternative anti-cytokine therapy with comparable efficacy in patients with potential risks of steroid administration. Patients with febrile fever at admission may benefit from ruxolitinib administration. Funding: Ruxolitinib was obtained from Novartis through Managed Access Program (MAP).