A multimodal sexual dysfunction intervention versus enhanced usual care for survivors of haematopoietic stem-cell transplantation: a single-centre, open-label, randomised clinical trial.

Background: Sexual dysfunction is a common complication affecting survivors of haematopoietic stem-cell transplantation (HSCT). Interventions to address sexual health in survivors of HSCT are limited. We aimed to assess the efficacy of a multimodal sexual dysfunction intervention for improving sexual health, quality of life (QOL), and psychological outcomes in survivors of HSCT.

RGI-2001 for the Prophylaxis of Acute Graft-Versus-Host Disease Following Allogeneic HCT.

RGI-2001, a liposomal glycolipid that binds CD1d receptor of antigen-presenting cells, can activate invariant natural killer T cells and stimulate cytokine-dependent proliferation of regulatory T-cells (Tregs). This open-label, single-arm, multicenter phase 2b trial evaluated the safety and efficacy of RGI-2001 in combination with standard graft-versus-host disease (GVHD) prophylaxis in participants receiving myeloablative allogeneic hematopoietic cell transplantation (HCT) for hematologic malignancies. RGI-2001 was infused at a dose of 100 ug/kg for six weekly doses starting on Day 0 of HCT.

Clinical presentation, management, and outcome of TIAN in CNS lymphoma treated with CD19-CAR T-cell Therapy.

Tumor inflammation-associated neurotoxicity (TIAN) was recently proposed as a unique complication of immunotherapy in brain tumor patients. Here, we report a first comprehensive characterization of TIAN in CNS lymphoma (CNSL) patients treated with CD19-directed chimeric antigen receptor T-cells (CD19-CAR). TIAN occurred in 10/56 (17.

Refinement of Day 28 Treatment Response Criteria for Acute GVHD: A Collaboration Study of the JSTCT and MAGIC.

Overall response (OR) that combines complete (CR) and partial responses (PR) at day (D) 28 is the conventional endpoint for acute GVHD trials. Since PR includes heterogeneous clinical presentations, reclassifying PR could produce a better endpoint. Patients in the primary treatment cohort from JSTCT were randomly divided into training and validation sets.

Impact of transplant conditioning, NPM1 mutations, and measurable residual disease in FLT3-ITD acute myeloid leukemia.

We conducted a post-hoc analysis of data from BMT CTN 1506 (MORPHO), a randomized trial of gilteritinib versus placebo as post-transplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 co-mutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD-negative pre-HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC versus RIC.

Multisite Randomized Trial of Inpatient Palliative Care Intervention for Patients Undergoing Hematopoietic Stem Cell Transplantation.

Purpose: Patients undergoing hematopoietic stem cell transplantation (HSCT) and their caregivers endure immense physical and psychological symptoms, which result in quality-of-life (QOL) impairments during HSCT.

Methods: We conducted a multisite randomized trial among adults undergoing autologous or allogeneic HSCT at three academic institutions. Patients were randomly assigned to an inpatient palliative care (PC) intervention or usual care.

Real-world evidence of duvelisib and romidepsin in relapsed/refractory peripheral and cutaneous T-cell lymphomas.

Patients with relapsed or refractory (R/R) peripheral T-cell lymphomas (PTCL) require lineage-specific therapies to bridge to hematopoietic stem cell transplantation (HSCT). A previous phase 1/2 study of duvelisib/romidepsin (duv/romi) reported an overall response rate (ORR) of 58% and a complete response rate (CRR) of 42% with reduced grade 3 to 4 transaminitis (14%). We report real-world duv/romi outcomes in a multicenter, 38-patient R/R PTCL cohort.

Sexual Health in Hematopoietic Stem Cell Transplantation Survivors.

Background: Sexual dysfunction is a common complication affecting the majority of hematopoietic stem cell transplant (HSCT) survivors. However, data on the relationships between sexual health domains, patient-reported quality of life (QoL), and psychological distress remain limited.

Methods: We conducted secondary data analyses of baseline data from 2 randomized sexual health intervention clinical trials involving HSCT survivors who were at least 3 months post-HSCT and reported sexual dysfunction causing distress between February 2019 and February 2023.

Pharmacological Maintenance Therapies After Allogeneic Hematopoietic Cell Transplantation.

Disease relapse is the leading cause of failure for patients with hematological malignancies who have received allogeneic hematopoietic cell transplantation (HCT). Maintenance therapy administered after HCT is a promising strategy to reduce the incidence of relapse and enhance the curative potential of HCT. Historically, maintenance therapy was not possible due to off-target toxicities from conventional chemotherapy.

BMT-CARE App: A Randomized Controlled Trial of a Psychosocial Digital Application for Caregivers of Patients Undergoing Hematopoietic Stem-Cell Transplantation.

Purpose: Family and friend caregivers of patients undergoing hematopoietic stem-cell transplantation (HSCT) struggle with immense caregiving burden, leading to substantial quality of life (QOL) impairments and psychological distress. Yet, interventions to address caregivers' needs are limited.

Materials And Methods: We conducted a randomized controlled trial of a psychosocial digital application (BMT-CARE App) versus usual care for adult caregivers of patients with hematologic malignancies undergoing HSCT.

A phase I clinical trial of lenalidomide combined with bortezomib for acute myeloid leukemia or myelodysplastic syndrome relapsing after allogeneic stem cell transplantation.

Background: Allogeneic hematopoietic cell transplantation (HCT) may improve long-term survival in patients with MDS or AML but disease relapse following HCT is common, with limited subsequent treatment options and extremely poor post-relapse outcomes. Lenalidomide and bortezomib are therapies which, in this setting, may exert antiproliferative effects, enhance graft-vs-leukemia immune responses, and potentiate chemotherapeutic drugs.

Objectives: We sought to evaluate the safety and preliminary efficacy of bortezomib in combination with high dose lenalidomide in patients with AML or MDS relapsing after HCT.

Low rates of chronic graft-versus-host disease with ruxolitinib maintenance following allogeneic HCT.

Despite recent advances in graft-versus-host disease (GVHD) prophylaxis, novel approaches to effective prevention of chronic GVHD (cGVHD) remain of high importance. In this prospective, multicenter, phase 2 trial, ruxolitinib, an oral inhibitor of Janus kinase (JAK) 1 and 2, was administered as maintenance therapy after reduced-intensity allogeneic hematopoietic cell transplantation (HCT). GVHD prophylaxis consisted of tacrolimus and methotrexate.

Vedolizumab for prevention of lower-GI acute GVHD in the Japanese subgroup analysis of the phase 3 GRAPHITE study.

In the randomized, double-blind, phase 3 GRAPHITE study (NCT03657160), anti-αβ integrin antibody vedolizumab showed greater efficacy than placebo for prevention of lower-gastrointestinal (GI) acute graft-versus-host disease (aGVHD) after unrelated allogenic hematopoietic stem cell transplantation (allo-HSCT). This post hoc analysis assessed the efficacy and safety of vedolizumab versus placebo for lower-GI aGVHD prevention in Japanese and non-Japanese patients, when added to standard GVHD prophylaxis (calcineurin inhibitor + methotrexate/mycophenolate mofetil + / - anti-thymocyte globulin [ATG]). The analysis included 35 (18 vedolizumab-treated, 17 placebo-treated) Japanese and 298 (150 vedolizumab-treated, 148 placebo-treated) non-Japanese patients.

Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice.

Background: Adipose tissue plays a pivotal role in systemic metabolism and maintaining bodily homeostasis. Exosomes from adipose tissues, known as AT-Exos, are recognized as important messengers in the communication between adipose tissue and other organs. Despite this, the alterations in exosome composition and the functional disparities among depot-specific AT-Exos in obesity remain elusive.

A Digital Intervention to Address Sexual Health in Hematopoietic Stem Cell Transplant Survivors.

Background: Interventions to address sexual health in hematopoietic stem cell transplant (HSCT) survivors are limited.

Methods: We conducted a pilot randomized trial of a digital app, SHIFT (Sexual Health and Intimacy Following Transplant), to address sexual dysfunction in HSCT survivors who were ≥3 months post autologous or allogeneic HSCT. Patients were randomly assigned to SHIFT or enhanced usual care.

Single-cell dynamics of breakthrough toxicities after anakinra prophylaxis for axicabtagene ciloleucel in lymphoma.

Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy is limited by cytokine release syndrome (CRS) and neurotoxicity (NT). We sought to use once-daily prophylactic anakinra, an interleukin-1 (IL-1) receptor antagonist, to prevent CRS/NT that would require hospitalization (grade ≥2) in patients receiving axicabtagene ciloleucel for large-cell lymphoma, with the goal of facilitating outpatient therapy and management. Our study, in line with others, demonstrates that once-daily prophylactic anakinra is insufficient to prevent the development of toxicities that would require hospitalization in most patients.

Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML.

BMT CTN (Blood and Marrow Transplant Clinical Trials Network) 1506 ("MORPHO") was a randomized study of gilteritinib compared with placebo as maintenance therapy after hematopoietic cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary end point was to determine the impact on survival of before and/or after HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD.

Measurable residual mutated IDH1 before allogeneic transplant for acute myeloid leukemia.

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. Persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplant (alloHCT) associates with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remain incompletely defined.

Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia.

Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively.

Toxicities and outcome after CD19-directed chimeric antigen receptor T-cell therapy for secondary neurolymphomatosis.

Lymphomatous infiltration of the peripheral nervous system (PNS), termed neurolymphomatosis, represents a distinct extranodal non-Hodgkin lymphoma variant with dismal outcome. CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy has emerged as a safe and effective treatment for B-cell lymphomas. We aimed to assess toxicity and efficacy of CD19-CAR T-cells in neurolymphomatosis.