Efficacy of Ruxolitinib in the management of chronic GVHD.

Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for hematological diseases, with success rates improving due to advancements in conditioning regimens and new anti-graft versus host disease (GVHD) drugs. Ruxolitinib, an oral selective Janus kinase (JAK) 1 and 2 inhibitor has been used to mitigate the effects of various inflammatory and myeloproliferative syndromes, given the JAK kinase pathway's central role in cytokine signaling during inflammatory and immune processes. In this study we aimed to assess ruxolitinib's efficacy in patients with chronic GVHD (cGVHD).

Optimal timing and impact of allogeneic peripheral blood stem cell transplantation in adult T-cell lymphoblastic lymphoma: insights from a large cohort multi-center real-world study in Shanghai.

In this real-world study, 153 adult T-cell lymphoblastic lymphoma (T-LBL) patients from sixteen centers in Shanghai were enrolled. Out of them, 103 (67.3%) achieved complete remission (CR).

The safety and efficacy of stem cell therapy for diabetic peripheral neuropathy in animal studies: A systematic review and meta-analysis.

Diabetic peripheral neuropathy (DPN) is the most common form of diabetic neuropathy, representing 75% of cases and posing a substantial public health challenge. Emerging evidence from animal studies indicates that stem cell therapy holds significant promise as a potential treatment for diabetic neuropathy. Nevertheless, a comprehensive evaluation of the safety and efficacy of stem cell therapy for DPN in animal studies remains outstanding.

An In-Depth Insight into Clinical, Cellular and Molecular Factors in COVID19-Associated Cardiovascular Ailments for Identifying Novel Disease Biomarkers, Drug Targets and Clinical Management Strategies.

COVID-19 was initially identified as a respiratory system disorder, but it has been reported to interact with and influence the cardiovascular system, in addition to many other body systems. Although COVID-19-associated cardiovascular (CV) complications are common, resulting in high acute phase mortality and a large number of morbidities in the chronic phase, thus severely impacting patients' quality of life and health outcomes, yet clinical, cellular, and molecular biological factors underlying the pathophysiology of cardiovascular complications associated with COVID-19 are poorly understood. This review investigates putative underlying clinical factors as well as cellular and molecular biological mechanisms by which COVID-19 leads to acute CV complications, including state-of-the-art genomic sequencing-based findings, and assessing the long-term CV consequences of COVID-19, aiming to shed light on developing strategies for differential diagnosis, risk prognostic stratification, prevention, and clinical management of CV sequels in COVID-19 patients.

Health-related values discussions with patients undergoing allogeneic and autologous stem cell transplant: Feasibility and acceptability of an early primary palliative care intervention.

Background: Hematopoietic stem cell transplant (HSCT) has curative potential but also relatively high morbidity and mortality. Patients have multidimensional palliative care (PC) needs throughout the transplant process. However, PC is not routinely offered to patients with hematologic malignancies.

What should be the optimal dose of post-transplantation cyclophosphamide for GVHD prophylaxis in allogeneic stem cell transplantation?

Objectives: In this study, we aimed to compare the engraftment days, graft versus host disease (GVHD) development, relapse and overall survival (OS) rates in patients using variable intensity conditioning regimens with two different post-transplant cyclophosphamide (PTCy) doses for hematological malignancies.

Material And Methods: We retrospectively analyzed 162 patients who have had PTCy at a dose of 25 mg/kg × 2 and 50 mg/kg × 2 between 2018 and 2024. Patients were divided in 2 groups; PTCy dose with 25 mg/kg × 2 (Group 1, n = 45) and PTCy dose with 50 mg/kg × 2 (Group 2, n = 117).

Abatacept Induces Long-Term Reconstitution of the B-Cell Niche in a Patient With CTLA-4 Haploinsufficiency: A Case Report.

Objectives: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency is a rare genetic condition characterized by development of immune cytopenia, hypogammaglobulinemia, and/or lymphoproliferative disorder, as well as multiple autoimmunity. Treatment with abatacept was shown to alleviate autoimmune conditions, yet its long-lasting impact on bone marrow function remains undetermined.

Methods: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia.

Late Bone Marrow Mononuclear Cell Transplantation in Rats with Sciatic Nerve Crush: Analysis of a Potential Therapeutic Time Window.

After peripheral nerve injury, axon and myelin regeneration are key events for optimal clinical improvements. We have previously shown that early bone marrow mononuclear cell (BMMC) transplantation exerts beneficial effects on myelin regeneration. In the present study, we analyze whether there is a temporal window in which BMMCs migrate more efficiently to damaged nerves while still retaining their positive effects.

The Evolution of Treatment Policies and Outcomes for Patients Aged 60 and Older with Acute Myeloid Leukemia: A Population-Based Analysis over Two Decades.

Background: Acute myeloid leukemia (AML) is a malignancy of the bone marrow with a median age at diagnosis of 70 years. AML is difficult to treat, especially in older patients, among whom outcomes have historically been poor. Over the last two decades, a greater understanding of the molecular mechanisms of the pathology has led to the development of new drugs and multiple updates to treatment guidelines.

A practice-oriented genome-profiling study for acute myeloid leukemia using the novel HANDLE system: HM-screen-JAPAN02.

HM-SCREEN-Japan is a multicenter collaborative project in Japan to evaluate the clinical utility of a cancer genome panel in the treatment of acute myeloid leukemia (AML). The HM-SCREEN-JAPAN02 study used the Amoy Myeloid Panel with the HANDLE system, which enables efficient and rapid sequencing, as the genomic testing kit. The Amoy Myeloid Panel targets 53 genes with established clinical significance or high prevalence.

In patients with follicular lymphoma, delayed-onset neutropenia induced by anti-CD20 monoclonal antibodies frequently occurs during maintenance therapy and is preferentially associated with obinutuzumab.

The prevalence of anti-CD20 monoclonal antibody (MoAb)-associated delayed-onset neutropenia (DON) varies between 8 and 27%. Despite the wide use of MoAbs as maintenance in follicular lymphoma (FL), data regarding DON occurrence and clinical consequences are limited. This study assessed DON prevalence, severity and risk factors in FL patients during maintenance.

Efficacy of Midostaurin Combined With Intensive Chemotherapy in Core Binding Factor Leukemia: A Phase II Clinical Trial.

Samples from 34 adult patients newly diagnosed with core binding factor leukemia (CBFL) were collected both at the time of diagnosis and at relapse and were centrally analyzed. Eligible patients received either standard induction CT known as "3 + 7" or an equivalent regimen, according to the recruiting center's policy. Patients who achieved CR or CRi received 3 courses of high-dose ARA-C (Cytarabine) 3000 mg/m every 12 h on days 1, 3, and 5, along with midostaurin at the dose of 50 mg b.

The EASIX score as a predictor of sinusoidal obstruction syndrome and nonrelapse mortality in paediatric patients receiving allogeneic haematopoietic stem cell transplantation.

The endothelial activation and stress index (EASIX) score, calculated as [lactate dehydrogenase (LDH; U/L) × serum creatinine (mg/dL)]/platelets (10e9/L)], has been shown to be predictive of nonrelapse mortality (NRM) and endothelial complications in adults receiving allogeneic stem cell transplantation (allo-HSCT); however, definitive results are lacking for children. We retrospectively evaluated consecutive paediatric allo-HSCT recipients and calculated the log2 EASIX score every day from admission to day +35. In 167 allo-HSCT recipients, the EASIX score increased from before conditioning (-0.

Flavopiridol restores granulopoiesis in experimental models of severe congenital neutropenia.

Severe congenital neutropenia (CN) patients require life-long treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF), but some show no response. We sought to establish a therapy for CN that targets signaling pathways causing maturation arrest of granulocytic progenitors. We developed an isogenic induced pluripotent stem cell (iPSC) in vitro model of CN associated with ELANE mutations (ELANE-CN) and performed an in silico drug repurposing analysis of the transcriptomics of iPSC-generated hematopoietic stem and progenitor cells.

Impact of the COVID-19 outbreak on the field of hematopoietic cell transplantation in the Asia-Pacific region: APBMT Activity Survey 2020/2021.

COVID-19 became a global pandemic in 2020 and significantly affected the activity of hematopoietic cell transplants (HCT) worldwide. Despite these challenges, a total of 28,793 transplants, including 18,518 allogeneic and 10,275 autologous transplants, were performed in 719 facilities in 2020 in the Asia-Pacific (AP) region. This represented a 5.

Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study.

Background: The SIPPET randomized clinical trial showed that in previously untreated patients (PUPs) with severe hemophilia A, treatment with plasma-derived factor (F)VIII (pdFVIII) within the first 50 exposure days (EDs) was associated with a lower cumulative incidence of inhibitors than with recombinant FVIII (rFVIII). Switching to rFVIII beyond 50 EDs with pdFVIII is a treatment often implemented by many centers. The question is whether or not this switch may induce a risk of inhibitor development.

Protective environment strategies for hematopoietic stem cell transplantation: progress and prospects.

With the progress of hematopoietic stem cell transplantation technology, the reduction of pretreatment intensity, the shortening of bone marrow suppression time and the reduction of infection risk, as well as the prominent physical and psychological stress for doctors and patients caused by rigorous protection procedures, the strategies for protective environment need to be reconsidered. Regardless of whether total environment protection is implemented, there is no significant difference in the outcomes of chemotherapy patients with neutropenia. The advantages and disadvantages of total environment protection have been weighed and reviewed for patients receiving hematopoietic stem cell transplantation.

Haematopoietic gene therapy of non-conditioned patients with Fanconi anaemia-A: results from open-label phase 1/2 (FANCOLEN-1) and long-term clinical trials.

Background: Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients.

Methods: This was an open-label, investigator-initiated phase 1/2 clinical trial (FANCOLEN-1) and long-term follow-up trial (up to 7 years post-treatment) in Spain.

BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

Toward human uterus tissue engineering: Uterine decellularization in a non-human primate species.

Introduction: Uterus bioengineering offers a potential treatment option for women with uterine factor infertility and for mitigating the risk of uterine rupture associated with women with defective uterine tissue. Decellularized uterine tissue scaffolds proved promising in further in vivo experiments in rodent and domestic species animal models. Variations in the extracellular matrix composition among different species and adaptations of the decellularization protocols make it difficult to compare the results between studies.

"It's the Tide of Your Life": A Qualitative Study on Survivor Awareness and Understanding of Blood and Marrow Transplantation.

Objective: This paper describes blood and marrow transplantation (BMT) survivors' and carers' knowledge and understanding of BMT and long-term care requirements.

Methods: Semistructured, online interviews with 22 BMT survivors and 6 carers were used to collect qualitative data. Interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis.