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Key Points The incidence of acute cardiac toxicity remains low and manageable after matched allo-HCT in the era of PTCy prophylaxis.Older age, hypertension, arrhythmia, diabetes, and cardiac comorbidities increase this risk of cardiac toxicity but PTCy did not., Visual Abstract, Graft-versus-host disease (GVHD) is one of the leading causes of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). Posttransplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicity, and few studies have evaluated the cardiac toxicities that arise after PTCy. We completed a retrospective analysis of patients who underwent matched-donor allo-HCT at our institution and who received PTCy- or non-PTCy–based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after allo-HCT. We included 585 patients in our analysis and found that 38 (6.5%) experienced cardiac toxicity after allo-HCT. The toxicities included arrhythmias (n = 21), heart failure (n = 14), pericardial effusion (n = 10), and myocardial infarction or ischemia (n = 7). Patients who received PTCy had a 7.4% incidence of cardiac toxicity, whereas non-PTCy recipients had an incidence of 5.8% (P = .4). We found that age >55 years (P = .02) and a history of hypertension (P = .01), arrhythmia (P = .003), diabetes (P = .04), and cardiac comorbidities (P < .001) were significant predictors of cardiac toxicity, whereas none of the preparative and GVHD prophylaxis regimens were predictive. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity after allo-HCT. We found that a higher score correlated with an incidence of cardiac toxicity. Furthermore, the development of cardiac toxicity was associated with worse 1-year overall survival (OS) and NRM. The use of PTCy was associated with improvements in 1-year OS and NRM rates.

Brincidofovir (BCV) is a lipid conjugate of cidofovir with good oral bioavailability, enabling optimal intracellular levels of the active drug. Lower rates of nephrotoxicity and myelotoxicity make it a favorable alternative. Despite a greater safety profile among pediatric hematopoietic cell transplant recipients, the oral formulation has been associated with increased gastrointestinal toxicity in adult hematopoietic cell transplant recipients. Oral BCV continues to be developed as a countermeasure against smallpox, while a potentially safer intravenous preparation has been out licensed to another company. BCV has demonstrated great in vitro potency against double-stranded DNA viruses, especially adenovirus. Because of its importance for immunocompromised patients, this review aims to evaluate BCV’s clinical and safety profile to support its continued development.

Increasingly, patients age ≥65 years are undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). Although age alone is a well-documented predictor of overall survival (OS) and nonrelapse mortality (NRM), growing evidence suggests that poor functional status and frailty associated with aging may have roles as well. Our goal in the present study was to identify and improve these and other aging-related maladies by developing a multimodal supportive care program for older allo-SCT recipients. We designed and implemented a multimodal supportive care program, Enhanced Recovery in Stem Cell Transplant (ER-SCT), for patients age ≥65 years undergoing allo-SCT. The ER-SCT program consists of evaluation and critical interventions by key health care providers from multiple disciplines starting before hospital admission for transplantation and extending through 100 days post-allo-SCT. We determined the feasibility of implementing this program in a large stem cell transplantation center. After 1 year of ongoing process improvements, multiple evaluations, and enrollment, we found that a dedicated weekly clinic was necessary to coordinate care and evaluate patients early. We successfully enrolled 57 of 64 eligible patients (89%) in the first year. Our data show that a multimodal supportive care program to enhance recovery for older patients undergoing allo-SCT is feasible. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Allogeneic hematopoietic cell transplantation (HCT) remains the only curable option for adult patients with hematologic malignancies. According to guidelines published by the American Society for Transplantation and Cellular Therapy, allogeneic HCT should be offered to all intermediate- and high-risk patients with acute leukemia. While matched-related donor (MRD) grafts continue to be the preferred stem cell source for allogeneic HCT, studies comparing MRD grafts to matched-unrelated donor (MUD) grafts showed comparable outcomes in patients with acute leukemia. Unfortunately, for those without a suitable matched-related graft, the probability of finding a suitable matched-unrelated donor varies significantly depending on racial and ethnic background. With allogeneic HCT procedures increasing year after year due to the increased availability of suitable donors, each of these alternative donor sources merits special clinical considerations, specifically with regard to infections. Infections remain a significant cause of morbidity and mortality after allogeneic transplant, especially in those receiving alternative donor grafts. Due to the high-risk nature associated with these donor grafts, it is important to understand the true risk of developing infectious complications. While there are a multitude of infections that have been described in patients post-allogeneic HCT, this review seeks to focus on the incidence of cytomegalovirus (CMV) and invasive fungal infections (IFI) in adult patients receiving alternative donor source transplantation for hematologic malignancies.

Context There are concerns that the use of immune checkpoint inhibitors (ICIs) after allogeneic stem cell transplant (allo-SCT) may increase the incidence of acute graft-versus-host disease (aGVHD). Objective We report our experience with ICIs used after allo-SCT in AML/MDS patients with a focus on the impact of post-transplant cyclophosphamide (PTCy). Methods We retrospectively analyzed 16 AML and 5 MDS patients who received nivolumab (n=16) or ipilimumab (n=5) for disease relapse after allo-SCT at our institution. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results Median age 54 years; 12 patients (57%) received PTCy. Transplantation characteristics were comparable between the two groups (PTCy vs no-PTCy), except for lower hematopoietic stem cell comorbidity index noted in the PTCy group (91% vs. 37.5%, P=.04). The PTCy group had shorter median time from allo-SCT to ICI initiation (5 vs. 26 months, P=.04). Over a median follow-up of 5.3 months, the frequency of grade 2–4 aGVHD was 19% in the entire cohort and was lower in PTCy group (16% vs 22%, P=0.7). All aGVHD cases were noted following nivolumab initiation. In patients who developed aGVHD, the median time from allo-SCT to ICI initiation was 4 months in PTCy group vs 9 months in the non-PTCy group (P=.17). Median time from ICI initiation to aGVHD was 24 days (range, 12–31) in the entire cohort and 22 days in PTCy group vs 16 days in non-PTCy (P=.31). After controlling for comorbidities and time from transplant to ICI initiation, we found that PTCy was significantly associated with a 90% reduced risk of aGVHD (HR= 0.1; 95% CI: 0.02–0.6; P=.01). No chronic GVHD or grade ≥2 immune-related adverse events were reported. The PTCy group had a significantly longer median PFS (22.4 vs. 5.2 months, P=.02) and a trend toward longer median OS (22.4 vs. 5.2 months, P=.08). Fourteen patients (67%) died, and no deaths were attributed to aGVHD. Conclusions The use of ICI for AML/MDS relapse after allo-SCT may be a safe and feasible option. PTCy appears to decrease the incidence of aGVHD in this cohort of patients.

Background Older patients undergoing allogeneic stem cell transplant (SCT) have inferior outcomes. They have limited physiological reserves, which makes them more susceptible to toxic effects of conditioning regimens. Supportive care directed at maintaining and augmenting their limited functional reserve may reduce non-relapse mortality (NRM). We studied impact of a multidisciplinary supportive care and prehabilitation program (ER-SCT) and compared one-year NRM with a historical control group. Methods Between 1/1/15 and 9/30/18, 204 patients ≥ 65 years old underwent allogeneic SCT at our institution. ER-SCT program started on 10/1/17 and 57 of 64(89%) eligible patients participated during the first year. All 64 patients were included in the ER-SCT cohort, while patients treated between 1/1/15-9/30/17 were in the control group. ER-SCT program consisted of a prehabilitation phase prior to admission. Patients were evaluated by a multidisciplinary team consisting of a geriatrician, physical medicine and rehabilitation physician, physical therapist, occupation therapist, dietician, nurse, and a pharmacist specializing in SCT. Preexisting chronic conditions were optimized and recommendations were made for nutrition, exercise, and coping strategies. During hospitalization, fluid usage and medication choice / doses were optimized for older patients to prevent side effects such as fluid overload and delirium. Physical therapy, occupational therapy and nutrition counselling was continued. The team continued to follow and intervene as needed after discharge from the hospital. Results Median age was 68 (65-79) with 36 (18%) patients >than 70 years. Diagnoses included AML 96 (47%), MDS 57(28%), MPD 26 (13%), ALL 8(4%), and other 17 (8%). 103 (51%) had high or very high disease risk index (DRI). HCT-CI score was >3 in 80 (39%). Donor types included 127 (62%) matched unrelated, 57(28%) matched related and 20(10%) haploidentical. The NRM at 1 year was 13% in ER-SCT cohort vs 26% (p=0.03) in the control cohort. Multivariate analysis adjusting for GVHD prophylaxis and conditioning regimen, age, DRI, HCT-CI, donor type and graft source showed that ER-SCT HR=0.4 (0.2-0.9, P=0.02), comorbidity score Conclusion Although the data from this retrospective sequential cohort analysis cannot be conclusive, they do suggest that a multidisciplinary supportive care program (ER-SCT) may reduce NRM in older patients undergoing allogeneic SCT.

Introduction PTCy-based GVHD prophylaxis has emerged as an effective method in Allo-HCT. Cyclophosphamide has historically been associated with increased rates of cardiac toxicities. This potential complication plays a role in the choice of optimal GVHD prophylaxis. The cardiac toxicity profile of PTCy compared with non-PTCy GVHD prophylaxis in HLA-matched Allo-HCT setting is unclear. Methods We performed a retrospective analysis to evaluate cardiac toxicities after HLA-matched Allo-HCT between October 1, 2016 and April 1, 2019. Cardiac toxicity was defined as any documented arrhythmia, heart failure, cardiac event (cardiac arrest or myocardial infarction), pericarditis, or pericardial effusion that occurred between Day 0 and 100. Results A total of 585 consecutive adult patients met eligibility (Table 1). 38 unique patients developed a total of 52 cardiac toxicities. The median time to cardiac toxicity was 20 days in the PTCy and 15 days in the non-PTCy groups. Toxicities (Table 2) included arrhythmias (40%), heart failure (27%), pericardial effusions (19%), and cardiac events (13%). This distribution and severity of toxicity was comparable between groups. Similarly the cumulative incidence of cardiac toxicity was comparable between the PTCy and non-PTCy groups (7 vs. 6%, p=0.4). Predictors of cardiac toxicity are shown in table 1. In univariate analysis, the cardiac comorbidity composite (defined as the presence of arrhythmia, cardiac, or heart valve comorbidities obtained via HCT-CI score) was found to be the most significant predictor for the development of cardiac toxicity (p In multivariate analysis, the cardiac comorbidity composite maintained significance and this effect was augmented by the presence of diabetes and infection. Patients with the cardiac comorbidity composite who also had diabetes or infection had the highest incidence (37%, p Conclusion Our results demonstrate a low incidence of cardiac toxicity. Baseline cardiac comorbidities are associated with higher incidence of developing cardiac toxicities after Allo-HCT. PTCy-based GVHD prophylaxis does not appear to impact the development of cardiac toxicities after HLA-matched Allo-HCT and may be associated with survival benefit in patients who do experience toxicity.

Purpose Intravenous immune globulin (IVIG) is a high-cost medication used in a diverse range of settings. At many institutions, IVIG is dosed using total body weight (TBW). Recent evidence suggests that alternative dosing weights reduce waste without compromising clinical outcomes. The objective of this study was to quantify the waste reduction potential generated through the use of alternative IVIG dosing weights. Methods We performed a retrospective analysis of all IVIG doses administered from January 2011 through January 2016 to adults (≥18 years). TBW and height at the time of administration were used to calculate prescribed dose (g/kg), ideal body weight (IBW), and adjusted body weight (AdjBW). Three dosing methods were analyzed, as follows: use of AdjBW if TBW is >120% IBW (method 1), AdjBW for all doses (method 2), and IBW for all doses (method 3). Outcomes included potential IVIG use averted, direct drug cost savings, and reductions in outpatient infusion times for each method. Results A total of 9,918 doses were administered to 2,564 patients over 5 years, representing an average usage of 75,994 g/year. If dosing methods 1, 2, and 3 had been used, the annual use of IVIG would have decreased by 21.9% (16,658 g/year, p < 0.001), 24.2% (18,371 g/year, p < 0.001), and 35.9% (27,252 g/year, p < 0.001), respectively. This translates into average annual cost differences of $2.37 million, $2.62 million, and $3.89 million and average annual outpatient infusion time savings of 841 hours, 920 hours, and 1,366 hours, respectively. Conclusion IVIG dosing optimization through use of alternative dosing weights represents a significant source of waste reduction and cost reduction.

tudy Objective To evaluate the steady-state pharmacokinetic parameters of standard cefepime dosing regimens in a hematologic malignancy and hematopoietic cell transplant patient population with febrile neutropenia. Design Open-label, single-center, prospective pharmacokinetic study. Setting National Cancer Institute–designated cancer center. Patients Nine adults with hematologic malignancies or hematopoietic cell transplants who had febrile neutropenia and were admitted to a hematology-oncology service between January and July 2014. Intervention Patients received empirical cefepime 2 g every 8 hours, administered as a 30-minute intravenous infusion, for febrile neutropenia. Measurements and Main Results Steady-state cefepime serum concentrations were measured after at least 2 days of continuous therapy. Venous blood samples were intensively sampled between 0 and 8 hours after the start of the 30-minute infusion at steady state. Seven of the nine patients had a hematologic malignancy diagnosis of acute leukemia, lymphoma, or myeloma, and two patients had a germ cell tumor diagnosis. Noncompartmental analysis revealed mean ± SD parameters as follows at steady state: area under the plasma concentration–time curve from 0–8 hours 222.9 ± 72.9 mg hour/L, maximum concentration 120.9 ± 21.8 mg/L, clearance 9.7 ± 3.7 L/hour, apparent volume of distribution 19.2 ± 4.65 L, and elimination half-life 1.4 ± 0.3 hours. A one-compartment pharmacokinetic model identified a mean ± SD volume of distribution of 20.9 ± 1.3 L and an elimination rate constant of 0.39 ± 0.03 hour−1. The mean estimated percentage of time that drug concentration remains above the pathogen minimum inhibitory concentration (fT>MIC) in serum was 55%, 77%, and 99% at MICs of 16, 8, and 4 mg/L, respectively. Conclusion Patients with hematologic malignancies or hematopoietic cell transplants who had febrile neutropenia demonstrated homogeneous calculated cefepime volumes and clearances. The population parameters presented in this study may aid in the calculation of patient-specific fT>MIC for similar patients.

Background: Allogeneic hematopoietic stem cell transplantation (alloHCT) remains a curative approach for patients with AML/MDS. Still, up to 50 % of patients relapse after alloHCT. Immune checkpoint inhibitors (ICI) are being used in the post-transplant setting to reverse the immune dysfunction that contributes to AML/MDS relapse. However, a major concern with using ICI post alloHCT is the increased risk of graft versus host disease (GVHD). A variety of pre- and post- transplant factors can play a crucial role in exacerbating GVHD. We performed a retrospective analysis to report our experience with ICIs used after alloHCT in AML/MDS patients with a focus on the impact of post-transplant cyclophosphamide (PTCy). Methods: In this study, we included 16 AML and 5 MDS patients treated with single-agent anti-PD-1 (nivolumab, n=16) or anti-CTLA-4 (ipilimumab, n=5) for disease relapse after alloHCT at our institution. The primary outcome was acute GVHD (aGVHD) following ICI initiation post alloHCT. Secondary outcomes were progression-free survival (PFS) and overall survival (OS) that were estimated using the Kaplan-Meier method. Results: Median patient age was 54 years (range, 29-77 years). Patients received a median of 2 doses of ICI therapy (range, 1 to 12). The median time from alloHCT to ICI initiation was 9.1 months (range 1.3-134.4 months). All patients had received myeloablative conditioning regimens. Donors were matched related in 9 (43%), matched unrelated in 9 (43%), and haploidentical in 3 (14%). Stem cell source was peripheral blood stem cells in 14 (67%) and bone marrow in 7 patients (33%). Twelve patients (57%) received PTCy as GVHD prophylaxis (PTCy group). Transplantation characteristics were comparable between the two groups (PTCy vs no-PTCy), except for lower median score of hematopoietic stem cell comorbidity index in PTCy group (median score of 1 (range,0-3) vs. median score of 3 (range,1-5), P=.04), and a shorter median time from alloHCT to ICI initiation (5 vs. 26 months, P=.04) noted in PTCy group. Before initiation of ICI, 5 patients (24 %) had previously had GVHD. In the entire cohort, 4 patients (19 %) developed aGVHD following ICI initiation. All the 4 cases of aGVHD were reported following nivolumab initiation. Over a median follow up of 5.3 months, the frequency of grade 2-4 aGVHD was 19%. The frequency of grade 1 to 2 and grade 3 to 4 aGVHD were 9.5% and 9.5%, respectively, with a median time from initiation of nivolumab to onset of aGVHD of 24 days (range, 12-31 days), and a median time from alloHCT to nivolumab-related aGVHD of 188 days (range,109-419 days). The median number of nivolumab doses to aGVHD was 2 doses (range, 1-8 doses). No chronic GVHD or grade > 2 immune-related adverse events were reported. The frequency of grade 2-4 aGVHD was not influenced by stem cell source, donor type, age at transplant, and previous history of GVHD, but was affected by post-transplant GVHD prophylaxis. Specifically, patients receiving PTCy had a lower observed cumulative incidence of grade 2 to 4 aGVHD than patients who did not receive PTCy (16% vs 22%, P=.07). After controlling for comorbidities and time from transplant to ICI initiation, we found that PTCy was significantly associated with a 90% reduced risk of aGVHD (HR= 0.1; 95% CI: 0.02 - 0.6; P=.01). Of the 13 evaluable patients who received nivolumab, 4 patients (31%) had an objective response, including 3 patients achieving a complete response (CR) and 1 patient achieving a partial response. The other 9 patients (69%) had no response. Of the 5 patients who received ipilimumab, only 1 patient (20 %) achieved a CR. The other 4 patients (80%) had progression of disease. There was no significant difference between the clinical responses in patients who received PD-1 inhibitor versus CTLA-4 inhibitor (P= 0.65). Patients receiving PTCy had a significantly longer median PFS (22.4 vs. 5.2 months, P=.02), and a trend toward longer median OS (22.4 vs. 5.2 months, P=.08). Fourteen patients (67%) died, and no deaths were related to aGVHD. Conclusions: The use of ICI for AML/MDS relapse after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of aGVHD in this cohort of patients. Given the small number of patients involved in our study, further investigations with a larger number of patients in prospective trials are needed to determine the magnitude of the of PTCy effect on reducing aGVHD after ICI. Disclosures Rafei: United States Provisiona: Patents & Royalties: I have a filed patent. Popat:Bayer: Research Funding; Novartis: Research Funding. Mehta:Kadmon: Research Funding; CSL Behring: Research Funding; Incyte: Research Funding. Konopleva:Amgen: Consultancy; Agios: Research Funding; Sanofi: Research Funding; Rafael Pharmaceutical: Research Funding; AbbVie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Forty-Seven: Consultancy, Research Funding; Cellectis: Research Funding; Calithera: Research Funding; Ablynx: Research Funding; Kisoji: Consultancy; Ascentage: Research Funding; Eli Lilly: Research Funding; F. Hoffmann La-Roche: Consultancy, Research Funding; AstraZeneca: Research Funding; Stemline Therapeutics: Consultancy, Research Funding; Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical. Oran:Celgene: Consultancy; Arog Pharmaceuticals: Research Funding; ASTEX: Research Funding. Ravandi:Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Xencor: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Macrogenics: Research Funding; Orsenix: Consultancy, Honoraria, Research Funding. Garcia-Manero:Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amphivena Therapeutics: Research Funding; Acceleron Pharmaceuticals: Consultancy, Honoraria; AbbVie: Honoraria, Research Funding; Merck: Research Funding; Jazz Pharmaceuticals: Consultancy; H3 Biomedicine: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Onconova: Research Funding; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Alousi:Incyte: Honoraria, Research Funding; Alexion: Honoraria; Therakos: Research Funding. Daver:Trillium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Servier: Research Funding; Genentech: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trovagene: Research Funding; Fate Therapeutics: Research Funding; ImmunoGen: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees. Champlin:Genzyme: Speakers Bureau; DKMS America: Membership on an entity's Board of Directors or advisory committees; Cytonus: Consultancy; Omeros: Consultancy; Johnson and Johnson: Consultancy; Actinium: Consultancy; Takeda: Patents & Royalties. Diab:Bristol Myers Squibb: Research Funding; Pfizer: Research Funding; Apexigen: Research Funding; Idera Therapeutics: Research Funding; Nektar Therapeutics: Research Funding.

Acute cellular rejection (ACR) is a major early complication after lung transplantation (LT) and is a risk factor for chronic rejection. Induction immunosuppression has been used as a strategy to reduce early ACR. Recently, our LT program changed our primary induction protocol from basiliximab with standard maintenance immunosuppression to alemtuzumab induction with reduced dose maintenance immunosuppression. The objective of this study was to compare incidence of ACR after this change in the first 6 months after transplantation.A retrospective, cohort review of patients 18 years or older, which received their first LT between January 2010 and September 2012.The primary outcome was comparison of average lung biopsy scores at 6 months. Secondary outcomes included development of grade A2 or higher rejection, infectious outcomes, overall graft and patient survival. At 6 months, the average biopsy score was significantly lower in the alemtuzumab group than the basiliximab group (0.12 ± 0.29 vs 0.74 ± 0.67; P0.0001) (Table 2). Grade 2 or higher rejection was significantly higher in the basiliximab group (P0.0001).Alemtuzumab provided superior outcomes in regard to average biopsy score and lower incidence of grade 2 or higher rejection at 6 months. There were no differences in infectious complications or overall graft or patient survival between the 2 groups.

Alterations in cefepime pharmacokinetic (PK) exposure and decreased bacterial susceptibility increase the risk of treatment failure. The impact of susceptible-dose-dependent (SDD) minimum inhibitory concentrations (MICs), i.e. 4-8 µg/mL, on target attainment rates for cefepime in febrile neutropenia (FN) is unclear. We sought to identify optimal cefepime regimens against SDD cefepime MICs in FN using a modelling and simulation approach. Creatinine clearance (CLCr) and body surface area (BSA) covariate-adjusted models of clearance were evaluated. Monte Carlo simulations representing 10 000 patients were completed to assess various dosing strategies (i.e. 3-8 g/day infused over 0.5-24 h, replaced every 6-24 h) and predict probabilities of target attainment (PTAs) for unbound cefepime. Nine patients received cefepime 2 g every 8 h (q8h) (0.5-h infusion). A two-compartment PK model with BSA- and CLCr-adjusted clearance was fit to the data. Mean population values for total clearance (6.3 ± 1.1 L/h), intercompartmental clearance (6.9 ± 2.8 L/h), and central (14.8 ± 3.8 L) and peripheral (10.9 ± 4.6 L) distribution volumes were all estimated with