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.

Outpatient CAR T-Cell Therapy as Standard of Care: Current Perspectives and Considerations.

Chimeric antigen receptor T-cell therapy (CAR-T) has altered the treatment landscape of several hematologic malignancies. Until recently, most CAR-T infusions have been administered in the inpatient setting, due to their toxicity profile. However, the advent of new product constructs, as well as improved detection and management of adverse effects, have greatly increased the safety in administering these therapies. CAR-T indications continue to expand, and inpatient administration is associated with increased healthcare resource utilization and overall cost. Therefore, transitioning CAR-T administration to the outpatient setting has been of great interest in an effort to improve access, reduce financial burden, and improve patient satisfaction. Establishment of a successful outpatient CAR-T requires several components, including a multidisciplinary cellular therapy team and an outpatient center with appropriate clinical space and personnel. Additionally, clear criteria for outpatient administration eligibility and for inpatient admission with pathways for prompt toxicity evaluation and admission, and toxicity management guidelines should be implemented. Education about CAR-T therapy and its associated toxicities is imperative for all clinical staff, as well as patients and their caregivers. Finally, rigorous financial planning and close collaboration with payers to ensure equitable access, while effectively managing cost, are essential to program success and sustainability. This review provides a summary of currently published experiences, as well as expert opinion regarding implementation of an outpatient CAR-T program.

Real-world analysis of tumor lysis syndrome in patients started on venetoclax combination for acute myeloid leukemia.

INTRODUCTION: Venetoclax is utilized with low-dose cytarabine or a hypomethylating agent for the treatment of acute myeloid leukemia. Clinical trials report a risk of tumor lysis syndrome and the package insert recommends a venetoclax dose ramp-up at the initiation. The purpose of this study was to evaluate the risk of tumor lysis syndrome in a large population of patients with acute myeloid leukemia outside of a clinical trial and evaluate the incidence of hospital-acquired complications during inpatient ramp-up. METHODS: We performed a retrospective study of adult patients with acute myeloid leukemia receiving venetoclax with a hypomethylating agent or low-dose cytarabine. The primary outcome was the incidence of tumor lysis syndrome. Secondary outcomes included risk factors for tumor lysis syndrome, length of admission, and incidence of hospital-acquired complications. RESULTS: One hundred thirteen patients were included. Although all patients were given some form of prophylaxis, the incidence of tumor lysis syndrome was 8.8%. All were laboratory tumor lysis syndrome; one with hyperuricemia, nine with hypocalcemia, and ten with hyperphosphatemia. Six patients received sevelamer. Tumor lysis syndrome was resolved in all cases. No clinical tumor lysis syndrome occurred. Hepatic dysfunction, tumor lysis syndrome high-risk stratification, higher baseline white blood cell count, and lactate dehydrogenase levels were more common in the tumor lysis syndrome group. Hospital-acquired complications reached 13% in those directly admitted for dose ramp-up. CONCLUSIONS: Tumor lysis syndrome was uncommon and manifested as minor lab abnormalities. White blood cell count continues to be an indicator of risk for tumor lysis syndrome. Those who present with an elevated white blood cell or are otherwise at high risk for tumor lysis syndrome should be admitted for ramp-up. Otherwise, initiation and monitoring of venetoclax are feasible in the outpatient setting.