Evaluating antibiotic de-escalation for autologous stem cell transplant patients with febrile neutropenia in a real-world clinical setting.

BACKGROUND: Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown. Accumulating evidence suggests that de-escalation of BSA in select patients may decrease duration of BSA exposure without compromising clinical outcomes such as infection, recurrent fever, and readmission. With this, a de-escalation protocol was implemented at Vanderbilt University Medical Center (VUMC) to identify autologous SCT patients who may benefit from early de-escalation of BSA. OBJECTIVES: The objectives of this study were to analyze the impact of early empiric antibiotic de-escalation on the duration of BSA as well as its impact on the incidence of recurrent fever and documented infection in autologous SCT patients. STUDY DESIGN: This was a single-center, retrospective study evaluating patients older than 18 years of age who underwent autologous SCT and experienced an episode of FN from January 2018 to December 2022 at VUMC (N = 195). The protocol was initiated on January 1, 2020, to de-escalate BSA back to prophylaxis in stable neutropenic patients determined to have a fever of unknown origin. The primary outcome was the number of BSA days within 30 days. Secondary clinical outcomes included recurrent fever, documented infection, readmission, 30-day mortality, and 90-day non-relapsed mortality (NRM). Outcomes were compared across pre- and post-protocol groups with a Wilcoxon rank sum test, Pearson chi-square test, or regression analysis as appropriate. RESULTS: The median BSA duration was 4.7 and 2.7 days in the pre- and post-protocol groups, respectively (p <0.001). Recurrent fever (14.2% vs. 16.0%, p = 0.726), documented infection (1.7% vs. 6.7%, p = 0.068), and readmission (13.3% vs. 22.7%, p = 0.091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% vs. 1.3%, p = 0.736) nor 90-day NRM (0.8% vs. 1.3%, p = 0.736) differed. CONCLUSIONS: The implementation of an early de-escalation protocol for autologous SCT patients who develop FN was associated with a reduction in duration of BSA compared to the pre-protocol group without a significant difference in readmission, recurrent fevers, and documented infections. This study adds to existing evidence that early de-escalation of BSA in FN patients with a fever of unknown origin who are afebrile and clinically stable is safe and reduces unnecessary antibiotic use.

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.

The Efficacy and Safety of Methylnaltrexone for the Treatment of Postoperative Ileus.

BACKGROUND: Postoperative ileus (POI) is a surgical complication resulting in increased morbidity and length of stay (LOS). Usual care for POI includes bowel rest and gastric decompression. It has been questioned if methylnaltrexone (MNTX), a peripheral opioid antagonist, could be used as treatment for POI. The purpose of this study was to determine if MNTX is effective and safe for POI treatment. METHODS: This single-center, retrospective cohort study included patients ⩾ 18 years with a POI. Patients with acute colonic pseudo-obstruction, small bowel obstruction, and gastrointestinal malignancy were excluded. The intervention was MNTX administration. The primary outcome was time to ileus resolution. Secondary outcomes included LOS, duration of nasogastric tube, total parenteral nutrition requirement, and incidence of gastrointestinal perforations. RESULTS: 110 patients were included in the analysis; 28 received MNTX. Time to ileus resolution was 9.9 days for the MNTX group and 11.4 days for the control group (P = .38). Duration of gastric decompression was 4.6 days for the MNTX group and 4.2 days for the control group (P = .71). Length of stay was 19.9 days for the MNTX group and 19.7 days for the control group (P = .96). The percentage of TPN requirement was 17.9% in the MNTX group and 22.0% in the control group (P = .65). No gastrointestinal perforations were observed in either group. CONCLUSION: For the treatment of POI, MNTX did not significantly reduce time to resolution of ileus, LOS, duration of gastric decompression, or TPN requirements. However, no gastrointestinal perforations were seen, indicating that MNTX may be safely used in these patients.