Guadecitabine improved relapse-free survival in high-risk acute myeloid leukemia and myelodysplastic syndrome patients after transplant: phase II results from a single center.

This phase 2, single-center clinical trial evaluated the efficacy and safety of guadecitabine, with or without donor lymphocyte infusion, following allogeneic stem cell transplantation (allo-SCT) in adult patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The study had three treatment cohorts based on disease status post-transplant. Cohort 1 included patients with hematological relapse after transplant (n=13).

Tagraxofusp maintenance post-hematopoietic stem cell transplantation provides long-term survival and manageable safety for a patient with blastic plasmacytoid dendritic cell neoplasm.

Presented here is the case of a 68-year-old woman with blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with tagraxofusp (TAG) maintenance therapy post-allogeneic hematopoietic stem cell transplantation (allo-HCT). Prior to allo-HCT, the patient was treated with hydroxyurea and mini-CVD (cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate (Methotrexate) and cytarabine) + venetoclax + TAG for 5 cycles, which induced morphologic complete remission with minimal residual disease. After allo-HCT, the patient had persistent cytogenic abnormalities 45,XX,der(7)add(7)(p13)del(7)(q11.

Inflammatory Markers and Microbiome Dysbiosis in Hematopoietic Cell Transplant Recipients with Lung Graft-versus-Host Disease.

Bronchiolitis obliterans (BOS) is a manifestation of pulmonary chronic graft-versus-host disease (cGVHD) and is a devastating complication of allogeneic hematopoietic stem cell transplantation (HCT). Early detection and treatment of BOS may improve outcomes, but biomarkers that accurately identify BOS early are lacking. We aimed to determine whether certain validated cGVHD markers could also accurately diagnose BOS as compared with patients without BOS and with or without extrapulmonary cGVHD.

A Phase 2 Trial of CPX-351 Combined With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia.

Outcomes in patients with relapsed/refractory (RR) AML are poor. We sought to investigate if CPX-531 in combination with venetoclax (CPX + VEN) was tolerable and effective in RR AML. This was a single institution phase 1b/2 trial of CPX + VEN.

Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study.

Belumosudil (KD025), an oral, selective, Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) inhibitor, is approved for third-line treatment of chronic graft-versus-host disease (cGVHD). Previous studies demonstrated that ROCK2 inhibition reduces blood interleukin-17 (IL-17) activity and promotes regulatory T-cell (Treg cell) recovery. However, these studies did not evaluate immune responses within cGVHD-affected tissues.

Impact of posttransplant cyclophosphamide-based GVHD prophylaxis in patients 70 years and older: an update from BMT CTN 1703.

Allogeneic hematopoietic cell transplant (allo-HCT) is underutilized in adults aged ≥70 years. Morbidity, often driven by graft-versus-host disease (GVHD), is considered a major barrier to its use. The BMT CTN 1703 trial (ClinicalTrials.

Allogeneic NK cells with a bispecific innate cell engager in refractory relapsed lymphoma: a phase 1 trial.

Outcomes of patients with CD30-positive (CD30) lymphomas have improved with the advent of brentuximab vedotin (BV) and, in Hodgkin lymphoma, anti-PD1 checkpoint inhibitors (CPI). However, there is a need for new therapies for patients with tumors refractory to both BV and CPI, who face dismal outcomes. AFM13-a CD30/CD16A bispecific antibody-activates natural killer (NK) cells to kill CD30 cells.

Steroid Refractory Acute GVHD: The Hope for a Better Tomorrow.

Steroid-refractory acute graft-versus-host disease (SR-AGVHD) presents a significant barrier to successful outcomes following allogeneic hematopoietic cell transplantation (HCT), despite advancements in GVHD prophylaxis and management. While ruxolitinib therapy has shown improved response rates, survival benefits remain elusive. This review explores the definitions and proposed distinct pathophysiology and treatment landscape of SR-AGVHD.

Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant.

Successful hematopoietic cell transplant requires immunosuppression to prevent graft-versus-host disease (GVHD), a lethal, T-cell-mediated post-transplant complication. The phase 3 BMT CTN 1703 trial demonstrated superior GVHD-free/relapse-free survival for post-transplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis versus tacrolimus/methotrexate (Tac/MTX), but did not improve overall survival. To compare T-cell biology between GVHD prophylaxis regimens, 324 patients were co-enrolled onto BMT CTN 1801 (NCT03959241).

Maintenance therapy with oral decitabine plus cedazuridine after allogeneic stem cell transplantation for myelodysplastic syndrome.

Disease relapse remains the primary challenge for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndromes. Maintenance therapies with hypomethylating agents are under investigation for use in mitigating relapse in high-risk patients. In this retrospective study, we assessed the safety and efficacy of oral decitabine- cedazuridine maintenance in 18 high-risk myelodysplastic syndromes patients post-HSCT.

Restrictive Ventilatory Defects Following Hematopoietic Stem Cell Transplant Are Associated With Increased Mortality.

Introduction: Hematopoietic cell transplantation (HCT) can potentially cure hematologic malignancies, but despite advancements in HCT regimens and graft-versus-host disease (GVHD) management, post-HCT complications, remain a major challenge. The epidemiology of post-HCT pulmonary impairment causing restrictive ventilatory defect (RVD) has not been examined. This study investigates the incidence, etiology, and impact of new-onset RVD following HCT on overall survival (OS) and non-relapse mortality (NRM).

Enhancement of High-Dose Chemotherapy and Autologous SCT with the PARP Inhibitor Olaparib for Refractory Lymphoma.

Purpose: More active high-dose chemotherapy (HDC) regimens are needed for autologous stem cell transplantation (ASCT) for refractory lymphomas. Seeking HDC enhancement with a PARP inhibitor, we observed marked synergy between olaparib and vorinostat/gemcitabine/busulfan/melphalan (GemBuMel) against lymphoma cell lines, mediated by the inhibition of DNA damage repair. Our preclinical work led us to clinically study olaparib/vorinostat/GemBuMel with ASCT.

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.

Outcomes of Patients With Treated Secondary Acute Myeloid Leukemia: A High-Risk Subtype That Warrants an Independent Prognostic Designation.

Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN.

Incidence of bacterial blood stream infections in patients with acute GVHD.

Bacterial bloodstream infections (BSI) can be a substantial contributor to complications of GVHD treatment. The aim of this study was to determine the risk for BSI from neutrophil engraftment through day 100 post transplant in patients with acute GVHD (AGVHD) based on organ involvement and severity. Patients (n = 4064) who underwent an allogeneic hematopoietic stem cell transplant (HCT) reported to the CIBMTR registry were analyzed.

High activity of the new myeloablative regimen of gemcitabine/clofarabine/busulfan for allogeneic transplant for aggressive lymphomas.

Refractory aggressive lymphomas can be treated with allo-SCT, pursuing a graft-vs-lymphoma effect. While reduced intensity conditioning is safe, tumors often progress rapidly, indicating the need for more active conditioning regimens. The preclinical synergy we saw between gemcitabine (Gem), clofarabine (Clo) and busulfan (Bu) against lymphoma cell lines led us to study Gem/Clo/Bu clinically.

Decreased Transfusions in Premenopausal Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation Given Leuprolide According to an Abnormal Uterine Bleeding Algorithm.

Purpose: Abnormal uterine bleeding (AUB) during allogeneic hematopoietic stem-cell transplantation (HSCT) leads to an increased need for transfusions. We developed an algorithm for the management of AUB that incorporated leuprolide and oral contraceptive pills (OCPs). Our aim was to evaluate whether treatment according to this algorithm reduced the number of transfusions.

Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus.

CT strain metrics allow for earlier diagnosis of bronchiolitis obliterans syndrome after hematopoietic cell transplant.

Bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is associated with substantial morbidity and mortality. Quantitative computed tomography (qCT) can help diagnose advanced BOS meeting National Institutes of Health (NIH) criteria (NIH-BOS) but has not been used to diagnose early, often asymptomatic BOS (early BOS), limiting the potential for early intervention and improved outcomes. Using pulmonary function tests (PFTs) to define NIH-BOS, early BOS, and mixed BOS (NIH-BOS with restrictive lung disease) in patients from 2 large cancer centers, we applied qCT to identify early BOS and distinguish between types of BOS.

Lower intensity therapy with cladribine/low dose cytarabine/venetoclax in older patients with acute myeloid leukemia compares favorably with intensive chemotherapy among patients undergoing allogeneic stem cell transplantation.

Background: Allogeneic stem cell transplantation (SCT) remains the best consolidative modality in most patients with acute myeloid leukemia (AML). Along with factors directly pertaining to SCT, pretransplantation disease control, performance status, and prior treatment-related complications are important factors that affect posttransplantation survival outcomes.

Methods: The authors compared the survival outcomes of patients ≥60 years of age treated on the phase 2 clinical trial of venetoclax (Ven) added to cladribine (CLAD) and low dose cytarabine (LDAC) alternating with azacitidine (CLAD/LDAC/Ven arm) (NCT03586609) who underwent allogeneic SCT in first remission to a retrospective cohort of patients ≥60 years of age who underwent SCT after intensive chemotherapy.