UNASSIGNED: Chronic graft-versus-host disease (cGvHD) is a serious late complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT).
UNASSIGNED: This multicenter analysis determined the cumulative incidence (CI) of cGvHD and late acute GvHD (laGvHD) and its impact on transplantation-related mortality (TRM), relapse (R), and overall survival (OS) in 317 patients [296 adults, 21 pediatrics (<12 years of age)] who underwent their first allo-HSCT in 2017.
UNASSIGNED: The CI of laGvHD was 10.5% in adults and 4.8% in pediatrics, and the CI of cGvHD was 43.0% in all adult transplant patients and 50.2% in the adult at-risk cohort at the study end. The onset of cGvHD was de novo in 42.0% of patients, quiescent in 52.1%, and progressive in 5.9%. In adults, prophylactic use of antithymocyte globulin or posttransplant cyclophosphamide was associated with a significantly lower incidence of cGvHD (28.7%) vs. standard prophylaxis with calcineurin inhibitors (30.6%) and methotrexate/mycophenolate mofetil (58.4%) (all p < 0.01). TRM was significantly higher in patients with aGvHD (31.8%) vs. cGvHD (12.6%) and no GvHD (6.3%) (all p = 0.0001). OS in the adult at-risk cohort was significantly higher in patients with cGvHD (78.9%) vs. without (66.2%; p = 0.0022; HR 0.48) due to a significantly lower relapse rate (cGvHD: 14.5%; without cGvHD: 27.2%; p = 0.00016, HR 0.41). OS was also significantly higher in patients with mild (80.0%) and moderate (79.2%) cGvHD vs. without cGvHD (66.2%), excluding severe cGvHD (72.7%) (all p = 0.0214).
UNASSIGNED: The negative impact of severe cGvHD on OS suggests a focus on prevention of severe forms is warranted to improve survival and quality of life.

Characterisation of the novel HLA-C*14:02:01:31 allele in a 21-year-old Greek bone marrow donor.

HLA-C*04:01:01:182 differs from the HLA-C*04:01:01:06 allele by one nucleotide substitution in the 5\'UTR.

BACKGROUND Fanconi anemia (FA) is a genetic disorder that impairs the function of the bone marrow and predisposes individuals to aplastic anemia. The condition is caused by mutations in genes responsible for DNA repair. People with FA have an increased risk of developing tumors due to DNA damage. Flat-cell carcinomas of the head, neck, esophagus, and genital organs are often observed in individuals with FA. CASE REPORT A 31-year-old man with Fanconi anemia and a history of bone marrow transplantation was admitted to the General Surgery Department due to elevated levels of the CEA marker. Before the transplantation, chromosomal anomalies, bone marrow hypoplasia, kidney agenesis, and bone defects were noted. After the transplantation, he developed a skin rash. He was also diagnosed with squamous cell carcinoma of the lip and chronic conditions, including cholestatic liver damage, hypertension, and hypothyroidism. During the diagnostic process, computed tomography showed signs of Barrett\'s esophagus, numerous polyps in the stomach and intestines, and a nodular formation measuring 4.5×5×5.5 cm in the right iliac region. Laparoscopy revealed a neoplasm of the appendix with numerous metastases on the inner abdominal wall and omentum. Histological analysis confirmed mucinous appendiceal cancer. The patient was discharged for palliative treatment at the Oncology Center with a final diagnosis of appendiceal cancer, mucinous type, grade G3. This case underscores the importance of early and comprehensive cancer screening in individuals with FA, particularly those with a history of bone marrow transplantation. CONCLUSIONS This clinical case underscores the critical importance of thorough and timely cancer diagnosis in individuals with this genetic pathology.

BACKGROUND: Germinal testicular tumors are the most common malignant neoplasm in men around 20 to 34 years. Even though they are unusual, they have increased incidence in the last decade; they have an excellent prognosis and overall survival at five years, approximately 95%. Divergent data exists regarding treatment options in patients with first, second, and third relapses with conventional therapy. Some studies describe the possible benefit of using high-dose chemotherapy associated with a bone marrow transplant with variable results.
METHODS:  The present study describes clinical outcomes, clinical response, mortality, overall survival, and progression-free survival to two years in a group of patients with germinal malignant tumors, seminoma versus non-seminomatous with evidence of progression of the disease at first, second, or third conventional chemotherapy regimens, and who received high dose chemotherapy and bone marrow transplantation at the National Cancer Institute between 2010 and 2021.
RESULTS: A retrospective observational study of case series showed that 57% of patients in third-line therapy received high-dose chemotherapy and bone marrow transplantation, with progression disease median time from diagnosis more than two years. Patients in the post-graft period presented infectious complications (71%). The most common were febrile neutropenia (29%) with a mortality rate of 71% (n=5), progression-free survival of 2.3 months, and overall survival of 7.4 months.
CONCLUSIONS:  These results show that in this group of patients, regimens with high-dose chemotherapy associated with bone marrow transplants, have a worse prognosis compared to other cohorts of patients, and may not be the best candidates for this rescue therapy.

BACKGROUND: There is no clear evidence on the comparative effectiveness of bone-marrow mononuclear cell (BMMNC) vs. mesenchymal stromal cell (MSC) stem cell therapy in patients with chronic heart failure (HF).
METHODS: Using a systematic approach, eligible randomized controlled trials (RCTs) of stem cell therapy (BMMNCs or MSCs) in patients with HF were retrieved to perform a meta-analysis on clinical outcomes (major adverse cardiovascular events (MACE), hospitalization for HF, and mortality) and echocardiographic indices (including left ventricular ejection fraction (LVEF)) were performed using the random-effects model. A risk ratio (RR) or mean difference (MD) with corresponding 95% confidence interval (CI) were pooled based on the type of the outcome and subgroup analysis was performed to evaluate the potential differences between the types of cells.
RESULTS: The analysis included a total of 36 RCTs (1549 HF patients receiving stem cells and 1252 patients in the control group). Transplantation of both types of cells in patients with HF resulted in a significant improvement in LVEF (BMMNCs: MD (95% CI) = 3.05 (1.11; 4.99) and MSCs: MD (95% CI) = 2.82 (1.19; 4.45), between-subgroup p = 0.86). Stem cell therapy did not lead to a significant change in the risk of MACE (MD (95% CI) = 0.83 (0.67; 1.06), BMMNCs: RR (95% CI) = 0.59 (0.31; 1.13) and MSCs: RR (95% CI) = 0.91 (0.70; 1.19), between-subgroup p = 0.12). There was a marginally decreased risk of all-cause death (MD (95% CI) = 0.82 (0.68; 0.99)) and rehospitalization (MD (95% CI) = 0.77 (0.61; 0.98)) with no difference among the cell types (p > 0.05).
CONCLUSIONS: Both types of stem cells are effective in improving LVEF in patients with heart failure without any noticeable difference between the cells. Transplantation of the stem cells could not decrease the risk of major adverse cardiovascular events compared with controls. Future trials should primarily focus on the impact of stem cell transplantation on clinical outcomes of HF patients to verify or refute the findings of this study.

Hematopoietic stem cell transplantation can deliver therapeutic proteins to the central nervous system (CNS) through transplant-derived microglia-like cells. However, current conditioning approaches result in low and slow engraftment of transplanted cells in the CNS. Here we optimized a brain conditioning regimen that leads to rapid, robust, and persistent microglia replacement without adverse effects on neurobehavior or hematopoiesis. This regimen combines busulfan myeloablation and six days of Colony-stimulating factor 1 receptor inhibitor PLX3397. Single-cell analyses revealed unappreciated heterogeneity of microglia-like cells with most cells expressing genes characteristic of homeostatic microglia, brain-border-associated macrophages, and unique markers. Cytokine analysis in the CNS showed transient inductions of myeloproliferative and chemoattractant cytokines that help repopulate the microglia niche. Bone marrow transplant of progranulin-deficient mice conditioned with busulfan and PLX3397 restored progranulin in the brain and eyes and normalized brain lipofuscin storage, proteostasis, and lipid metabolism. This study advances our understanding of CNS repopulation by hematopoietic-derived cells and demonstrates its therapeutic potential for treating progranulin-dependent neurodegeneration.

New available drugs allow better control of systemic symptoms associated with myelofibrosis (MF) and splenomegaly but they do not modify the natural history of progressive and poor prognosis disease. Thus, hematopoietic stem cell transplantation (HSCT) is still considered the only available curative treatment for patients with MF. Despite the increasing number of procedures worldwide in recent years, HSCT for MF patients remains challenging. An increasingly complex network of the patient, disease, and transplant-related factors should be considered to understand the need for and the benefits of the procedure. Unfortunately, prospective trials are often lacking in this setting, making an evidence-based decision process particularly arduous. In the present review, we will analyze the main controversial points of allogeneic transplantation in MF, that is, the development of more sophisticated models for the identification of eligible patients; the need for tools offering a more precise definition of expected outcomes combining comorbidity assessment and factors related to the procedure; the decision-making process about the best transplantation time; the evaluation of the most appropriate platform for curative treatment; the impact of splenomegaly; and splenectomy on outcomes.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) can potentially cure malignant blood disorders and benign conditions such as haemoglobinopathies and immunologic diseases. However, allo-HSCT is associated with significant complications. The most common and debilitating among them is graft-versus-host disease (GVHD). In GVHD, donor-derived T cells mount an alloimmune response against the recipient. The alloimmune response involves several steps, including recognition of recipient antigens, activation and proliferation of T cells in secondary lymphoid organs, and homing into GVHD-targeted organs. Adhesion molecules on T cells and endothelial cells mediate homing of T cells into lymphoid and non-lymphoid tissues. In this study, we showed that Von Willebrand factor (VWF), an adhesion molecule secreted by activated endothelial cells, plays an important role in mouse models of GVHD. We investigated the effect of the VWF-cleaving protease ADAMTS13 on GVHD. We found that ADAMTS13 reduced the severity of GVHD after bone marrow transplantation from C57BL6 donor to BALB/C recipient mice. A recombinant VWF-A2 domain peptide also reduced GVHD in mice. We showed that ADAMTS13 and recombinant VWF-A2 reduced the binding of T cells to endothelial cells and VWF in vitro, and reduced the number of T cells in lymph nodes, Peyer\'s patches and GVHD-targeted organs in vivo. We identified LFA-1 (αLβ2) as the binding site of VWF on T cells. Our results showed that blocking T-cell homing by ADAMTS13 or VWF-A2 peptide reduced the severity of the GVHD after allo-HSCT, a potentially novel method for treating and preventing GVHD.

In bone marrow transplantation (BMT), hematopoiesis-reconstituting cells are introduced following myeloablative treatment, which eradicates existing hematopoietic cells and disrupts stroma within the hematopoietic tissue. Both hematopoietic cells and stroma then undergo regeneration. Our study compares the outcomes of a second BMT administered to mice shortly after myeloablative treatment and the first BMT, with those of a second BMT administered to mice experiencing robust hematopoietic regeneration after the initial transplant. We evaluated the efficacy of the second BMT in terms of engraftment efficiency, types of generated blood cells, and longevity of function. Our findings show that regenerating hematopoiesis readily accommodates newly transplanted stem cells, including those endowed with a robust capacity for generating B and T cells. Importantly, our investigation uncovered a window for preferential engraftment of transplanted stem cells coinciding with the resumption of blood cell production. Repeated BMT could intensify hematopoiesis reconstitution and enable therapeutic administration of genetically modified autologous stem cells.