Background: Antibiotic allergy de-labeling using penicillin allergy skin testing (PAST) can reduce the use and cost of alternative, non-β-lactam antibiotics in general inpatient populations. This strategy's role in hematopoietic stem cell transplant (HSCT) recipients is unclear. Methods: This study aimed to determine the effect of a pre-transplant PAST protocol on antibiotic use, days of therapy (DOT), and cost in an immunocompromised population at a single center from 7/1/2010-2/1/2019. Patients who received chimeric antigen receptor (CAR) T-cell therapy and those who underwent transplantation in the outpatient setting were excluded. Results: Of 1560 patients who underwent inpatient HSCT during the study period, 208 reported β-lactam allergy (136/844 [16%] pre-and 72/716 [10%] post-implementation; P < .001). PAST was performed on 7% and 54% of HSCT recipients preand post-implementation, respectively. Only two positive PAST were noted. There were no adverse reactions to PAST. There were no significant differences in the disease and transplant characteristics between the two groups. Days of therapy and cost of alternative antibiotics significantly decreased post-implementation (mean 788 vs 627 days, P = .01; mean $24 425 vs $17 518, P = .009). Conclusion: Penicillin allergy skin testing adjudicates reported β-lactam allergy in HSCT recipients, lowering use, DOT, and cost of alternative antibiotics and promoting effective formulary agents to treat immunocompromised HSCT recipients.

Obesity continues to be an increasing global health issue contributing to the complexity of chemotherapy dosing in the field of SCT. Investigation into the optimal dosing weight used to calculate chemotherapy doses in obese patients undergoing SCT is limited and inconclusive. Our single-center, retrospective study compared safety and efficacy outcomes by body mass index (BMI) for 476 adult lymphoma patients who underwent auto-SCT with a myeloablative chemotherapeutic regimen of BU, CY and etoposide dosed using adjusted body weight. Three weight groups categorized based on BMI were defined: normal/underweight ⩽ 24.9 kg/m 2 , overweight 25-29.9 kg/m 2 and obese ⩾ 30 kg/m 2 . Severity of mucositis, incidence of secondary malignancy, incidence of bacteremia and median hospital length of stay did not differ among the groups. The median times to absolute neutrophil count and platelet recovery were 10 days (P = 0.75) and 14 days (P = 0.17), respectively. Obese patients had a lower 100-day mortality compared with other weight groups, although this did not translate into an OS benefit. OS and disease relapse were similar among the groups. Our study demonstrates that use of adjusted body weight to calculate chemotherapy doses does not negatively have an impact on outcomes in obese patients undergoing auto-SCT with BU, CY and etoposide.

High-dose busulfan (Bu) is an integral component of commonly used preparative regimens for both allogeneic and autologous transplantation. There is significant interest in comparing the efficacy and toxicity of administering Bu every 6 (Bu6) or every 24 hours (daily Bu). To facilitate a therapeutic dose-monitoring protocol, we transitioned from Bu6 to daily Bu dosing for patients with Hodgkin and non-Hodgkin lymphoma undergoing autologous stem cell transplantation (ASCT). Here, we retrospectively review outcomes of 400 consecutive eligible lymphoma patients who underwent ASCT from 2007 to 2013 with high-dose busulfan (Bu), cyclophosphamide (Cy), and etoposide (E). Bu was given at a fixed dose of either .8 mg/kg every 6 hours for 14 doses for 307 patients or a fixed dose of 2.8 mg/kg every 24 hours for 4 doses (days -9 through -6) for 93 patients who underwent transplantation after the transition from Bu6 to daily Bu was made. Toxicity was assessed using pulmonary and liver function tests (LFT) at specified time points before and after ASCT. Baseline patient and disease characteristics of patients dosed with Bu6 and daily Bu were similar. There was no significant difference in forced expiratory volume in 1 second or diffusing capacity of the lungs for carbon monoxide before and after transplantation in the Bu6 versus daily Bu cohorts. Changes in LFTs with daily Bu were not significantly different than those with Bu6. There were no differences in relapse, nonrelapse mortality, progression-free survival, or overall survival between Bu6 and Bu 24 administration schedules in univariable or multivariable analysis (P ≥ .34). For a subset of 23 patients who had first-dose Bu levels measured, we observed significant variation in an median estimated cumulative area under the curve (AUC) of 17,568 µM-minute (range, 12,104 µM-23,084 µM-minute). In conclusion, daily Bu with Cy/E is more convenient than Bu6, has equivalent outcomes, and results in no increase in either hepatic or pulmonary toxicity. Consistent with previous reports, there is a significant range of Bu AUC levels, with a standard deviation of 13%. These data provide rationale for our prospective clinical trial of real-time therapeutic dose monitoring of Bu.

BackgroundPenicillin allergy de-labeling can be an effective stewardship tool at reducing cost and the use of alternative non-β-lactam antibiotics. This study aimed to determine the effect of a pre-transplant penicillin allergy skin testing (PAST) protocol on antibiotic usage and costs in an immunocompromised hematopoietic cell transplant (HCT) population.MethodsWe conducted a retrospective study of adult HCT patients at the Cleveland Clinic from July 2010-September 2016. Routine AST for HCT patients reporting allergy to β-lactam antibiotics was implemented at our institution in July 2015. We compared days of antibiotic therapy (DOT) and antibiotic costs (AC) before and after the implementation of the AST protocol. Antibiotic usage for empiric treatment of suspected bacterial infection was captured as average DOT per 1000 patient days during the index hospitalization and AC were measured as dollars per 1000 patient days. Utilization of alternative antibiotics was compared with our standard formulary agent (piperacillin/tazobactam).ResultsAmong the 1108 HSCT during the study period (N = 871 pre-and N = 237 post-PAST) β-lactam allergy was reported by 178 patients (141 [16%] pre- and 37 [16%] post-PAST, P = 0.83). PAST was performed on 8% (11/141) and 76% (28/37) of patients pre- and post-implementation. Only 2 positive PAST were noted (one in each group). There were no adverse reactions to PAST. There was no significant difference in the disease and transplant characteristics between the two groups. Average DOT (760 vs. 588; P = 0.03) and AC ($23,559 vs. $14,179; P = 0.012) decreased for all alternative antibiotics except levofloxacin (see Figures 1 and 2). Usage and cost of our institutional empiric formulary agent increased after AST implementation.ConclusionThe use of PAST to adjudicate reported β-lactam allergy in patients undergoing HCT is an effective antimicrobial stewardship strategy to lower usage and cost of alternative antibiotics and can facilitate prescribing of effective standard formulary agents when treating immunocompromised HCT patients at high-risk for infection. The impact of penicillin allergy de-labeling on Clostridium difficile infection and antibiotic resistance merits evaluation in future studies.Disclosures All authors: No reported disclosures.

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