May, Heather P.

Abstract Rationale The periengraftment respiratory distress syndrome (PERDS) is an early important cause of morbidity following autologous hematopoietic cell transplantation (HCT). There are few contemporary data describing PERDS. Objectives To determine prevalence, risk factors, and outcomes of PERDS after autologous HCT. Methods This was a historical cohort study of adults undergoing autologous HCT at Mayo Clinic, Rochester, Minnesota, between 2005 and 2016. PERDS was defined as 1) respiratory failure requiring supplemental oxygen within 5 days on either side of the neutrophil engraftment date, 2) new pulmonary opacities on chest imaging, and 3) exclusion of an infectious or cardiac etiology to explain the clinical presentation. Results Of 3,473 patients undergoing autologous HCT, 167 (4.8%) developed PERDS. Radiographic changes preceded engraftment in 77% of cases. In a multivariable regression model, risk factors for PERDS included female sex (odds ratio [OR], 1.73; P = 0.001), the number of preengraftment platelet transfusions (OR, 1.22; P = 0.002), and more rapid engraftment (OR, 0.72 per day longer; P < 0.001). PERDS cases were more likely to be admitted to the intensive care unit (47.3% vs. 9.5%, P < 0.001) and require intubation (20.4% vs. 1.6%, P < 0.001). In an adjusted 100-day death analysis, those diagnosed with PERDS were more likely to die (hazard ratio, 3.1; 95% confidence interval, 1.5–6.2; P = 0.002). Conclusions PERDS is a common complication of autologous HCT and is associated with increased mortality and healthcare use. Radiographic evidence of pulmonary involvement precedes hematopoietic recovery. A larger number of platelet transfusions and more rapid engraftment appear to increase risk for PERDS.

Acute kidney injury (AKI) is common in those with newly diagnosed hematologic malignancies. Precipitants of AKI in this population may include tumor lysis syndrome, hypotension and other insults associated with acute illness. In a general population, AKI not only leads to short-term consequences like fluid, electrolyte and acid-base abnormalities, but each episode has been linked to worse long-term outcomes, including chronic kidney disease, cardiovascular events and death. In patients with malignancies, loss of kidney function may be additionally detrimental, as this can jeopardize eligibility for full dose or first line chemotherapy, transplantation or enrollment in clinical trials. The purpose of this study is to determine the impact of AKI on long-term loss of kidney function in patients newly diagnosed with aggressive lymphomas or acute leukemia. We performed a population-based cohort study using data from the Rochester Epidemiology Project (REP). The REP is a medical-record linkage system that integrates data for patients across multiple medical care providers in Olmsted County, MN and surrounding areas to facilitate long-term follow-up. Adults admitted to the hospital between 2005 and 2017 following a new diagnosis of acute leukemia or aggressive lymphoma were evaluated for the exposure of AKI. AKI was defined by the KDIGO serum creatinine (SCr) criterion (Stage 1: 1.5-fold increase from baseline or 0.3mg/dL increase in 48-hours; Stage 2: 2-fold increase from baseline; Stage 3: 3-fold increase from baseline, increase in SCr to >4mg/dL, or initiation of renal replacement therapy). Only the first episode of hospitalization was included. Cox proportional hazards regression was used to compare the primary outcome of loss of kidney function within 12 months of hospitalization [defined as ≥30% decline from baseline estimated glomerular filtration rate (eGFR)] in those with and without AKI. A subgroup analysis was performed in patients with a baseline eGFR <60 mL/min/1.73m2. eGFR calculations used the Chronic Kidney Disease Epidemiology Collaborative equation. Outcome evaluation began 90-days after hospitalization to establish chronicity and was defined only by outpatient SCr values. Within the REP cohort, 1,085 patients were hospitalized following a new diagnosis of acute leukemia or lymphoma who consented to the use of their medical records for research. Sixteen patients with pre-existing end-stage renal disease were excluded, leaving 1,069 included patients for analysis. The majority were white (n=1,002; 93.7%) males (n=624; 58.4%) with a mean (SD) age of 64 (18) years. Mean baseline SCr was 1.0 (0.4) mg/dL with a corresponding eGFR of 80 (27) ml/min/1.73m2. A total of 355 patients (33.2%) experienced AKI during the index hospitalization, most commonly a maximum stage of I (n=231; 21.6%). Stages II and III AKI occurred in 42 (3.9%) and 59 (5.5%) patients, respectively. Cumulative incidence of ≥30% loss of baseline eGFR in the 12 months following hospitalization was 67.9% (95% CI 56.8%-76.1%) for those with any AKI and 38.8% (95% CI 31.8%-45.1%) for those without AKI during the index hospitalization. Patients diagnosed with any stage AKI were more likely to experience this outcome compared to those without AKI (HR 2.6, 95% CI 2.2-3.5, p<0.001) in unadjusted analysis. Amongst those with a baseline eGFR ≤60 ml/min, no significant difference in the outcome was noted (HR 1.7, 95% CI 0.83-3.35, p=0.15). Patients with AKI during initial hospitalization following a new diagnosis of acute leukemia or aggressive lymphoma were significantly more likely to experience ≥30% loss of baseline eGFR in the 12 months following diagnosis. This highlights a critical need to identify interventions which prevent AKI and optimize renal recovery so as to decrease overall morbidity and preserve eligibility for desirable treatment options. Disclosures Barreto: FAST Biomedical, Inc: Consultancy. Leung:Prothena: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Omeros: Research Funding; Aduro: Membership on an entity's Board of Directors or advisory committees.

Background. Acute kidney injury (AKI) is a common complication of treatment with liposomal amphotericin B (LAmB). The trajectory of renal recovery after LAmB-associated AKI has not been well described, nor has effect of LAmB dose on recovery of renal function been explored. Objective. Characterize the pattern of renal recovery after incident AKI during LAmB and determine potential influencing factors. Methods. This retrospective cohort study analyzed patients who developed a ≥50% increase in serum creatinine while on LAmB. Patients were followed up until complete renal recovery or death or for 30 days, whichever occurred first. The primary outcome was complete renal recovery, defined as serum creatinine convalescence to within 10% of the patient’s pretreatment baseline. Multivariable modeling was used to identify independent predictors of renal recovery. Results. Ninety-eight patients experienced nephrotoxicity during LAmB, 94% of which received doses <7 mg/kg/day. Fifty-one patients at least partially recovered renal function and, of these, 32 exhibited complete recovery after a mean 9.8 ± 7.8 days. No statistical relationship was found between LAmB dose at the time of AKI or cumulative exposure to LAmB and the likelihood of renal recovery. Concomitant nephrotoxins, age, and pretreatment renal function did not modify this effect in multivariable analysis. Conclusion and Relevance. Our data suggests that LAmB dose did not impact the likelihood of renal recovery. Additional investigation is needed to confirm these findings when aggressive dosing strategies are employe. Additional research is also warranted to further characterize the course of recovery after LAmB-associated nephrotoxicity and comprehensive spectrum of renal outcomes.