Efficacy and safety of outpatient fludarabine, cyclophosphamide, and rituximab based allogeneic hematopoietic cell transplantation in adults with severe aplastic anemia.

The age effect in severe aplastic anemia (SAA) following allogeneic hematopoietic cell transplantation (HCT) favors the use of reduced intensity conditioning (RIC) regimens in older adults. We implemented a non-myeloablative regimen consisting of fludarabine, cyclophosphamide, and rituximab (FCR) to improve HCT outcomes in SAA. Patients who underwent first HCT for SAA utilizing an FCR regimen between January 2016 and May 2022 were included. Outcomes analyzed included time to engraftment, incidence of graft failure, GVHD, viral reactivation, disease recurrence, and GVHD-free, relapse-free survival (GRFS). Among 24 patients included, median age was 43.5 years (22-62) and a variety of donor types and stem cell sources were represented. At median follow-up of 26.9 months (2.4-72.7), no cases of grade III-IV acute (aGVHD) or severe chronic GVHD (cGVHD) were recorded. Viral reactivation was minimal, and there were no cases of graft failure or PTLD, with 100% disease-free and overall survival at last follow up. The estimate of 1-year GRFS was 86.3% (95% CI: 72.8-100%), with moderate cGVHD accounting for all events. The FCR regimen in SAA was well tolerated, even in older adults, with 100% disease-free survival with low GVHD and infection rates. These encouraging findings should be validated in larger prospective trials.

Prevention and management of acute toxicities from conditioning regimens during hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) remains the only curative option for several hematological malignancies. Its use has continued to grow, with an estimated 23,500 transplants performed annually in the United States alone. The acute toxicities that occur from conditioning chemotherapy can impact the peri-transplant period and have substantial implications on patients' tolerability and outcomes, irrespective of the treatment of their disease. Chemotherapy-induced nausea vomiting (CINV), mucositis, transplant-associated thrombotic microangiopathy (TA-TMA), and sinusoidal obstruction syndrome, also known as a veno-occlusive disease (SOS/VOD) can all have significant implications for patients. These acute complications begin with the start of conditioning chemotherapy and add to potential toxicity for patients throughout the early post-transplant period, from Day +30 for CINV, mucositis, and SOS, and which can continue through at least Day +100 with the onset of TA-TMA. These toxicities must be prevented and managed appropriately. This review will summarize the literature surrounding them and guide their management.

Controversies about immunoglobulin replacement therapy in HSCT recipients with hypogammaglobulinemia.

The efficacy of immunoglobulin replacement therapy (IgRT) has been demonstrated for primary immune deficiency diseases and hematological malignancies such as chronic lymphocytic leukemia (CLL) or multiple myeloma with hypogammaglobulinemia. Clinical development of anti-B cell therapies including a monoclonal antibody, bispecific antibody, or chimeric antigen receptor T-cell therapy which could result in severe hypogammaglobulinemia accelerates the argument of prophylactic use of IgRT. Clinical guidelines for CLL describe immunoglobulin administration in patients with a low IgG who have experienced a severe/repeated bacterial infection. The utility in hematopoietic stem-cell transplantation (HSCT) remains unknown. Although an early randomized trial demonstrated that IgRT decreased infection risk and transplant-related mortality after HSCT, subsequent clinical trials could not validate the benefit. Consequently, a meta-analysis did not show the benefit of IgRT in HSCT. Most of the available data derives from matched-related HSCT using myeloablative regimen, and the impact in haploidentical and cord blood transplantation, or reduced-intensity HSCT remains unknown. One crucial issue is that no studies exist for patients with only hypogammaglobulinemia after HSCT. Other challenges are heterogeneous patient characteristics, or immunoglobulin formulation, dosage, schedule, route and duration of IgRT. Without evidence in HSCT, it would be reasonable to follow the guidelines for other diseases with hypogammaglobulinemia.

Provider education program on the Khorana score to promote venous thromboembolism chemoprophylaxis in patients with gynecologic cancer.

OBJECTIVE: To evaluate the efficacy of a healthcare improvement initiative to improve provider compliance with the American Society of Clinical Oncology (ASCO) guidelines for venous thromboembolism chemoprophylaxis in patients with gynecologic cancer receiving chemotherapy. METHODS: A healthcare improvement initiative was implemented at our institution to improve compliance with American Society of Clinical Oncology venous thromboembolism chemoprophylaxis guidelines in patients receiving chemotherapy with a Khorana score ≥2. Baseline Khorana score and venous thromboembolism data were retrospectively collected for chemotherapy-naïve patients with gynecologic cancer initiating chemotherapy between December 2018 and November 2019. Data for the post-intervention period from December 2019 to December 2020 were captured prospectively. Primary outcome was compliance with American Society of Clinical Oncology guidelines. Secondary outcomes were incidence of venous thromboembolism and complications surrounding venous thromboembolism chemoprophylaxis. RESULTS: We identified 62 patients in the pre-implementation cohort. Approximately half had a Khorana score of ≥2 (52%). Median Khorana score was 2 (range 1-4). None of these patients received prophylactic chemoprophylaxis. Seven (11%) of these patients were diagnosed with venous thromboembolism. Multivariate logistic regression showed increasing Khorana score was associated with increased venous thromboembolism risk (OR 4.9, p=0.01). With cut-off Khorana score of 2, there was no significant increase in venous thromboembolism. However, with a cut-off Khorana score of 3, patients were 15 times more likely to have venous thromboembolism (OR 15.2, p=0.04). In the post-intervention cohort, 22 patients were eligible for chemoprophylaxis and 11 patients were given anticoagulation (50% compliance with guidelines), with no incidence of venous thromboembolism or adverse effects of therapy noted among those receiving chemoprophylaxis. CONCLUSION: Notifying providers of a patient's Khorana score improves compliance with American Society of Clinical Oncology guidelines for venous thromboembolism chemoprophylaxis among chemotherapy patients.

Outcomes and Predictors of Early Infection after Heart Transplantation.

BACKGROUND: Limited data exist on the incidence and outcome of early infection after orthotopic heart transplantation (OHT). The purpose of this study was to describe characteristics and outcomes of OHT recipients with an early infection and to identify predictors of such infections. METHODS: This retrospective, single-center study included patients greater than 18 years of age who underwent OHT from February 2009 to May 2014 and had an infection within 30 days of transplantation. Patient demographics, clinical variables, and outcomes were collected. Multivariable logistic regression was performed to identify independent predictors of infection. RESULTS: Of the 172 eligible OHT recipients, 51 (29.7%) had an early infection. The median time to diagnosis was five days, with gram-negative organisms being slightly more common (58.2%). No differences in mortality rate, rejection, or re-admission were found between the groups. Longer durations of mechanical ventilation and lengths of stay were found in the infection group (p < 0.001). Patients with an early infection also had a higher incidence of mechanical circulatory support, history of drive-line infection, longer duration of mechanical ventilation, continuous renal replacement therapy (CRRT), and delayed chest closure (p < 0.05 for all). Pre-OHT left-ventricular assist device (adjusted odds ratio [AOR] 2.53; 95% confidence interval [CI] 1.015-6.286; p < 0.046), pre-OHT extracorporeal membrane oxygenation (AOR 14.10; 95% CI 1.38-150.5; p = 0.026) and post-OHT CRRT (AOR 3.98; 95% CI 1.67-9.52; p = 0.002) were found to be independent risk factors for an early infection. A total of 90% of the available susceptibility panels for the gram-negative isolates (26/29) were resistant to the standard peri-operative cephalosporin given. CONCLUSIONS: Prior mechanical circulatory support and the acute need for CRRT may predispose OHT patients to an infection early in the post-operative period. Evaluation of peri-operative antimicrobial prophylaxis, based on an individual center's resistance panels, may be warranted.

Impact of Dose-Adjusted Melphalan in Obese Patients Undergoing Autologous Stem Cell Transplantation.

Limited guidance exists for dosing melphalan for autologous stem cell transplantation (ASCT) in the obese patient population, because the current literature reports conflicting clinical outcomes between obese and nonobese patients. In 2014, the American Society for Blood and Marrow Transplantation published conditioning chemotherapy dosing guidelines for obese patients and recommended dosing of melphalan using actual body weight (ABW) in the body surface area calculation. The practice at Barnes-Jewish Hospital has consistently been to dose melphalan using adjusted body weight (AdBW), with a 20% correction when a patient weighs ≥120% of his or her ideal body weight (IBW). The purpose of this study was to compare outcomes of melphalan ASCT in patients with multiple myeloma between obese (≥120% IBW) and nonobese (<120% IBW) populations. This retrospective, single-center study included adult patients with multiple myeloma undergoing first ASCT with melphalan conditioning between January 2009 and December 2012. Patient demographic data, transplantation characteristics, and clinical outcomes were collected. The primary outcome was 3-year event-free survival (EFS). Secondary outcomes included response at 100 days post-transplantation, 3-year overall survival, treatment-related mortality (TRM), time to neutrophil engraftment, and hospital length of stay (LOS). To ensure that melphalan dosage adjustment in the obese population did not impact efficacy, the primary outcome was assessed using a noninferiority design, with a predetermined noninferiority margin of 7%. Assuming a 70% 3-year EFS in the nonobese population, a noninferiority margin of 7%, a power of 80%, and an α value of .05, an analysis of 280 patients was required. A total of 270 patients, including 171 (63%) obese patients and 99 (37%) nonobese patients, met our inclusion criteria. Baseline characteristics were well matched between the 2 cohorts, including high-risk cytogenetics, disease severity at diagnosis, and use of maintenance therapy, with the only detectable differences related to weight itself. The 3-year EFS was 41% for the total cohort, with fewer events occurring in the obese cohort compared with the nonobese cohort (51% versus 40%; P = .0025). The 95% lower confidence limit established noninferiority. High-risk cytogenetics, disease severity at diagnosis, and therapy response pre- and post-ASCT were all associated with significantly shorter EFS. No between-group differences in TRM, time to engraftment, or hospital LOS were noted. This retrospective, single-center study found that using AdBW to dose melphalan in obese patients was not inferior to the nonobese population in terms of 3-year EFS. This study adds to the limited evidence on melphalan dosing and suggests that transplantation efficacy is not affected by AdBW dosing in obese patients. Further studies are needed to provide additional insight into the pharmacokinetic differences and best dosing practices for obese patients.