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Depletion of αβ T cells from the graft prevents graft-vs.-host disease (GVHD) and improves outcome of HSCT from haploidentical donors. In a randomized trial, we aimed to evaluate the safety and efficacy of low-dose memory (CD45RA-depleted) donor lymphocytes (mDLI) after HSCT with αβ T-cell depletion. A cohort of 149 children was enrolled, 76 were randomized to receive scheduled mDLI and 73 received standard care. Conditioning was based on either 12 Gy total body irradiation or treosulfan. Rabbit antithymocyte globulin was replaced by tocilizumab and abatacept. Primary end points were the incidence of acute GVHD grades II–IV and the incidence of cytomegalovirus (CMV) viremia. The incidence of grades II–IV aGVHD was 14% in the experimental arm and 12% in the control arm, p—0.8. The incidence of CMV viremia was 45% in the experimental arm and 55% in the control arm, p—0.4. Overall, in the total cohort 2-year NRM was 2%, cumulative incidence of relapse was 25%, event-free survival 71%, and overall survival 80%, without difference between the study arms. Memory DLI was associated with improved recovery of CMV-specific T-cell responses in a subcohort of CMV IgG seropositive recipients.

Hematopoietic stem cell transplantation (HSCT) is a curative option for children with high-risk acute lymphoblastic leukemia (ALL). This retrospective single-center study analyzed 236 pediatric ALL patients in complete remission who underwent allogeneic HSCT using ex-vivo T cell depletion between 2012 and 2021. The majority received haploidentical grafts ( n  = 202), while the remainder received matched unrelated donor (MUD) grafts ( n  = 34). At four years, event-free survival (EFS) and overall survival (OS) were 57% and 67%, respectively. Total body irradiation (TBI)-based conditioning was associated with significantly lower relapse rates and superior EFS compared to chemotherapy-based regimens. Non-relapse mortality (NRM) was low (9%), with no significant difference between donor types. Pre-transplant minimal residual disease (MRD) positivity and transplantation beyond first complete remission were independently associated with higher relapse and inferior survival. Chronic GVHD incidence was lower in patients receiving abatacept and tocilizumab instead of ATG. These findings confirm the safety and efficacy of ex-vivo T cell-depleted HSCT in pediatric ALL, with outcomes comparable between haploidentical and MUD donors. TBI-based conditioning and MRD negativity remain key prognostic factors for improved outcome.

The delayed recovery of adaptive immunity underlies transplant-related mortality (TRM) after αβ T cell-depleted hematopoietic stem cell transplantation (HSCT). We tested the use of low-dose memory donor lymphocyte infusions (mDLIs) after engraftment of αβ T cell-depleted grafts.A cohort of 131 pediatric patients (median age 9 years) were grafted with αβ T cell-depleted products from either haplo (n = 79) or unrelated donors (n = 52). After engraftment, patients received mDLIs prepared by CD45RA depletion. Cell dose was escalated monthly from 25 × 103 to 100 × 103/kg (haplo) and from 100 × 103 to 300 × 103 /kg (MUD). In a subcohort of 16 patients, T-cell receptor (TCR) repertoire profiling with deep sequencing was used to track T-cell clones and to evaluate the contribution of mDLI to the immune repertoire.In total, 343 mDLIs were administered. The cumulative incidence (CI) of grades II and III de novo acute graft-versus-host disease (aGVHD) was 5% and 2%, respectively, and the CI of chronic graft-versus-host disease was 7%. Half of the patients with undetectable CMV-specific T cells before mDLI recovered CMV-specific T cells. TCR repertoire profiling confirmed that mDLI-derived T cells significantly contribute to the TCR repertoire up to 1 year after HSCT and include persistent, CMV-specific T-cell clones.

Recovery of immunity is delayed in recipients of T-depleted grafts. Adoptive transfer of memory T-cells may improve immune response to common pathogens. A cohort of 53 patients with malignant ( n  = 36) and non-malignant conditions ( n  = 17) received TCR alpha/beta depleted grafts from haploidentical ( n  = 25) or MUD ( n  = 28) donors. Donor lymphocytes were depleted of CD45RA-positive cells. At a median of 48 days after transplantation, patients received DLI at 25 × 10 3 /kg CD3 cells from haploidentical or 100 × 10 3 /kg CD3 from MUD donors. Up to 3 doses of donor lymphocytes were administered at monthly intervals, escalating to 100 × 10 3 /kg in haploidentical transplants and 300 × 10 3 /kg in MUD transplants. At a median follow-up of 23 months, the cumulative incidence of de novo acute GVHD after DLI is 2% (1 of 43), while the rate of reactivation of preexisting aGVHD was 50% (5 of 10). The transplant-related mortality is 6%. The overall survival rates are 80% and 88% in malignant and non-malignant conditions, respectively. Among patients with absent CMV-specific immune reactivity at baseline ( n  = 31) expansion of CMV-specific T-cells was demonstrated in 20 (64.5%) within 100 days. Infusions of low dose donor memory T-lymphocytes are safe and constitute a simple measure to prevent infections in the setting of alpha/beta T cell-depleted transplantation.

This paper presents an analysis of 24 cases in which recombinant factor VIIa (rFVIIa) was used in the management of hemorrhage in patients with thrombocytopenia associated with hematologic malignancies. This is the largest case aggregation to date and focuses on preliminary experience in the off-label use of this hemostatic agent. Data were extracted from the international, Internet-based registry, www.haemostasis.com, accessed in September 2003. The search results were manually cross-checked against monthly summary reports. The physicians providing the cases were contacted individually to approve the use of their cases, supply any information missing from the database, and validate the data already held. Patients with acute myeloid leukemia, acute lymphoblastic leukemia, Hodgkin’s disease, non-Hodgkin’s lymphoma, Burkitt’s lymphoma, B-cell or T-cell lymphoma, or aplastic anemia received rFVIIa at total doses of between 18 and 1040 μg/kg body weight. Bleeding stopped in 11 of 24 (46%) patients, markedly decreased in 8 of 24 (33%) patients, and decreased in 4 of 24 (17%) patients. In most patients, the response was achieved within 2.5 hours of administration of rFVIIa. The use of rFVIIa was generally well tolerated—1 case of ischemic stroke was considered to be possibly related to rFVIIa administration, but this has yet to be confirmed. A review of these 24 cases submitted to the www.haemostasis.com database suggests that rFVIIa is beneficial in the management of hemorrhage in patients with thrombocytopenia and hematologic malignancies. This warrants further investigation in rigorously controlled clinical trials.

In this paper, we unveil a groundbreaking method to amplify full-text search lemmatization, utilizing the OpenCorpora dataset and a bespoke paradigm retrieval algorithm. Our primary aim is to streamline the extraction of a word's primary form or lemma - a crucial factor in full-text search. Additionally, we propose a compact dictionary storage strategy, significantly boosting the speed and precision of lemma retrieval.

Currently, when satellite data volumes grow rapidly and exceed petabyte values and their quality provides reliable analysis of long-term time series, traditional data handling methods assuming local storage and processing may be impossible to implement for small or distributed research teams. Thus, new methods based on modern web technologies providing access to very large distributed data archives are gaining increasing importance. Furthermore, these new data handling solutions should provide not just access but also analysis and processing features, similar to desktop solutions. This paper describes the VEGA-Science web GIS—an open-access novel tool for satellite data processing and analysis. The overview of its architecture and basic technical components is given, but most attention is paid to examples of actual system application for various applied and research tasks. In addition, an overview of projects using the system is given to illustrate its versatility and further development directions are considered.

IntroductionThe live-attenuated BCG vaccine is known to cause disseminated Mycobacterium bovis infection in patients with severe combined immunodeficiency (SCID). However, BCG-related post-hematopoietic stem cell transplantation (HSCT) immune reconstitution inflammatory syndromes, similar to those described in patients with HIV infections, are less-known complications of SCID.Patients and MethodsWe reported on 22 BCG-vaccinated SCID patients who had received conditioned allogeneic HSCT with TCRαβ+/CD19+ graft depletion. All BCG-vaccinated patients received anti-mycobacterial therapy pre- and post-HSCT. Post-transplant immunosuppression consisted of tacrolimus in 10 patients and of 8 mg/kg tocilizumab (d-1, + 14, + 28) and 10 mg/kg abatacept (d-1, + 5, + 14, + 28) in 11 patients.ResultsTwelve patients, five of whom had BCG infection prior to HSCT, developed BCG-related inflammatory syndromes (BCG-IS). Five developed early BCG-IS with the median time of manifestation 11 days after HSCT, corresponding with a dramatic increase of CD3+TCRγδ+ in at least two patients. Early BCG-IS was noted in only one out of 11 patients who received tocilizumab/abatacept and 4 out of 11 patients who did not. Seven patients developed late BCG-IS which corresponded to T cell immune recovery; at the time of manifestation (median 4.2 months after HSCT), the median number of CD3+ cells was 0.42 × 109/ and CD3+CD4+ cells 0.27 × 109/l. In all patients, late BCG-IS was controlled with IL-1 or IL-6 inhibitors.ConclusionBCG-vaccinated SCID patients undergoing allogeneic HSCT with TCRαβ+/CD19+ graft depletion are at an increased risk of early and late BCG-IS. Anti-inflammatory therapy with IL-1 and IL-6 blockade is efficient in the prevention of early and treatment of late BCG-IS.

A full-scale geophysical observatory in the North Caucasus, which was established to study volcanic activity in the Elbrus area, has been functioning for more than 10 years. Results of experimental studies performed at the observatory, located in the deep tunnel, are presented. Special attention is paid to the stability of metrologically significant parameters of precise information-measuring systems, taking into account different nature noises. Technical characteristics of installed geophysical instruments are given, and the principles of their operation are described. Examples of instrumental observations are also presented; for example, tidal deformations reflecting structural features of the geological environment in the area of the Elbrus volcanic edifice and associated with the presence of magmatic structures were investigated. It was shown that diurnal and semidiurnal harmonics observed in the microvariations of temperature can be caused, among other things, by the influence of tidal effects on the convective component of heat–mass transfer.