Graft-versus-host disease (GVHD) is a principal cause of morbidity following allogeneic hematopoietic cell transplantation (HCT). Standard therapy for GVHD, high-dose steroids, results in complete responses (CRs) in 35% of patients. Because tumor necrosis factor-␣ (TNF␣) is an important effector of experimental GVHD, we treated patients with newonset GVHD with steroids plus the TNF␣ inhibitor etanercept on a previously reported pilot trial (n ‫؍‬ 20) and a phase 2 trial (n ‫؍‬ 41). We compared their outcomes with those of contemporaneous patients with GVHD (n ‫؍‬ 99) whose initial therapy was steroids alone. Groups were similar with respect to age, conditioning, donor, degree of HLA match, and severity of GVHD at onset. Patients treated with etanercept were more likely to achieve CR than were patients treated with steroids alone (69% vs 33%; P < .001). This difference was observed in HCT recipients of both related donors (79% vs 39%; P ‫؍‬ .001) and unrelated donors (53% vs 26%; P < .001). Plasma TNFR1 levels, a biomarker for GVHD activity, were elevated at GVHD onset and decreased significantly only in patients with CR. We conclude that etanercept plus steroids as initial therapy for acute GVHD results in a substantial majority of CRs. This trial was referenced at www.clinicaltrials.gov as NCT00141713.(Blood.

VDD is highly effective for initial treatment of MM followed by SCT in appropriate patients, and it has a reasonable safety profile. Achievement of VGPR or better with this initial therapy predicted longer PFS, regardless of the consolidation therapy given.

Omidubicel is an ex vivo expanded hematopoietic progenitor cell, and non-expanded myeloid and lymphoid cell product derived from a single umbilical cord blood unit. We report results of a phase III trial to evaluate the efficacy of omidubicel compared to standard umbilical cord blood transplantation (UCBT). Between January 2017 and January 2020, 125 patients aged 13-65 with hematologic malignancies were randomized to omidubicel versus standard UCBT. Patients received myeloablative conditioning and graft versus host disease (GvHD) prophylaxis with a calcineurin inhibitor and mycophenolate mofetil. The primary endpoint was time to neutrophil engraftment. The treatment arms were well balanced and racially diverse. Median time to neutrophil engraftment was 12 days (95% CI 10-14 days) and 22 days (95% CI 19-25 days) (p&lt;0.001) for the omidubicel and control arms, respectively. The cumulative incidence of neutrophil engraftment was 96% and 89% for patients receiving omidubicel and control transplants, respectively. The omidubicel arm had faster platelet recovery (55% vs. 35% recovery by 42 days, p=0.028), a lower incidence of first grade 2/3 bacterial or invasive fungal infections (37% vs. 57%, p=0.027), and spent more time out of hospital during the first 100 days following transplant (median 61 vs. 48 days, p=0.005) than controls. Differences in GvHD and survival between the two arms were not statistically significant. Transplantation with omidubicel results in faster hematopoietic recovery and reduced early transplant-related complications as compared to standard UCBT. The results suggest that omidubicel may be considered as a new standard of care for adult patients eligible for UCBT.

Natural killer (NK) cell immunotherapy as a cancer treatment shows promise, but expanding NK cells consistently from a small fraction (∼ 5%) of peripheral blood mononuclear cells (PBMCs) to therapeutic amounts remains challenging. Most current ex vivo expansion methods use co-culture with feeder cells (FC), but their use poses challenges for wide clinical application. We developed a particle-based NK cell expansion technology that uses plasma membrane particles (PM-particles) derived from K562-mbIL15-41BBL FCs. These PM-particles induce selective expansion of NK cells from unsorted PBMCs, with NK cells increasing 250-fold (median, 35; 10 donors; range, 94 to 1492) after 14 days of culture and up to 1265-fold (n = 14; range, 280 to 4426) typically after 17 days. The rate and efficiency of NK cell expansions with PM-particles and live FCs are comparable and far better than stimulation with soluble 41BBL, IL-15, and IL-2. Furthermore, NK cells expand selectively with PM-particles to 86% (median, 35; range, 71% to 99%) of total cells after 14 days. The extent of NK cell expansion and cell content was PM-particle concentration dependent. These NK cells were highly cytotoxic against several leukemic cell lines and also against patient acute myelogenous leukemia blasts. Phenotype analysis of these PM-particle-expanded NK cells was consistent with an activated cytotoxic phenotype. This novel NK cell expansion methodology has promising clinical therapeutic implications.

Reduced-intensity conditioning (RIC) extends hematopoietic stem cell transplants (HSCT) to elderly or debilitated patients who are not candidates for HSCT. The incidence and outcomes of cardiac complications have been reported following myeloablative HSCT. We assessed the incidence and outcomes of cardiac complications in 278 recipients of RIC from July 2000 to July 2006. All patients received conditioning with BU, fludarabine and TBI. Patients were evaluated from conditioning therapy until 100 days after HSCT. Median age was 56 years. Cardiac events were defined as either one or more of the following: arrhythmias, myocardial infarction or congestive heart failure. Twenty-five patients developed arrhythmias at a median of 3 days post transplant, in 19 patients hemodynamic compromise occurred and mechanical ventilation was required in 15 patients. The arrhythmias included atrial fibrillation (n =17), atrial flutter (n =6) and supraventricular tachycardia (n =2). Troponin was elevated in 12 out of 25 patients. The mean brain natriuretic peptide was 679. All patients converted to a normal rhythm by medical therapy at a median of 2 days. Recurrence of arrhythmia occurred in 76% of patients. Day 100 mortality was 40% in this group. A history of high-dose anthracycline treatment and a low ejection fraction were risk factors for the development of cardiac complications.