Study Objective To determine whether there is a drug‐drug interaction precluding the concomitant use of levetiracetam and high‐dose methotrexate (HDMTX). Design Retrospective analysis. Setting Large academic tertiary care medical center. Patients Adult lymphoma patients who received HDMTX as a 4‐h infusion with or without concomitant levetiracetam. Measurements and Main Results Generalized estimating equations clustered on patient were used to assess each outcome. The primary outcome was the incidence of delayed MTX elimination (MTX level >1 µmol/L at 48 h). Secondary outcomes included incidence of acute kidney injury (AKI) and hospital length of stay (LOS). The 430 included patients receiving 1993 doses of HDMTX had a median (IQR) age of 66 (57.5, 72.6) years, 88 (20.5%) received concomitant levetiracetam with at least one dose of MTX, 267 (62.1%) were male, and 397 (92.3%) were Caucasian. HDMTX doses ranged from 1 to 8 g/m2. The most common lymphoma diagnoses were systemic diffuse large B‐cell lymphoma (DLBCL; 58.5%) and systemic DLBCL with central nervous system (CNS) involvement (32.8%). Rates of delayed elimination with and without levetiracetam were 13.4% and 16.3%, respectively (OR = 0.80, 95% CI 0.47–1.34, p = 0.39). AKI occurred in 15.6% and 17.0% of patients with and without concomitant levetiracetam, respectively (OR = 0.83, 95% CI 0.52–1.33, p = 0.28). The median LOS with and without levetiracetam was 4.2 and 4.1 days, respectively (p = 0.039). On multivariable analyses, only age, body surface area, diagnosis of systemic DLBCL with CNS involvement, serum creatinine, hemoglobin, total bilirubin, and dose of HDMTX were associated with delayed elimination. Conclusions High‐dose methotrexate administered with concomitant levetiracetam was not associated with increased risk for delayed MTX elimination or AKI. These results support that levetiracetam and HDMTX are safe for coadministration.

A Polymerase Chain Reaction-based diagnosis of Pneumocystis Pneumonia (PCP) and the need for anti-Pneumocystis prophylaxis in Hodgkin Lymphoma patients receiving chemotherapy requires further investigation. This retrospective, single-center, study evaluated 506 consecutive adult patients diagnosed with Hodgkin lymphoma receiving chemotherapy between January 2006 and August 2018. The cumulative incidence of PCP 1 year after start of chemotherapy was 6.2%

The reduced-intensity conditioning regimen, fludarabine and melphalan, is frequently used in allogeneic hematopoietic stem cell transplantation (HSCT). Melphalan and the active metabolite of fludarabine, F-ara-A, are excreted via the kidneys. Existing methods to assess clearance in this setting are based on serum creatinine, which has known limitations for glomerular filtration rate (GFR) estimation in patients with malignancy. Measured GFR (mGFR) may better predict drug dosing to mitigate toxicity and increase the chances of successful engraftment. The primary objective of this study was to assess the association between mGFR and risk for non-relapse mortality (NRM) in allogeneic HSCT patients receiving conditioning with fludarabine and melphalan. In the 109 included patients, mGFR < 65 ml/min/1.73m2 predicted a significantly higher rate of overall NRM (HR 2.13, 95% CI, 1.03-4.35, P = 0.04) and 1-year incidence of infection (HR 2.63, 95% CI, 1.54-4.55, P < 0.001) in addition to a significantly lower 2-year survival (P = 0.019). Kidney function estimated via eGFR and eCrCl did not correlate with post-transplant outcomes. These results suggest that mGFR is a promising approach for assessing clearance in allogeneic HSCT patients and may be preferred to standard creatinine-based eGFR strategies.

Rationale Bleomycin is a long-standing component of the primary combination chemotherapy for Hodgkin lymphoma. Bleomycin directly injures lung epithelia, causes interstitial and hypersensitivity pneumonitis, fibrosing alveolitis, and, through immune-suppression, places recipients at risk for Pneumocystis pneumonia (PCP). While these phenomena and their risk factors are relatively well described, there is a paucity of data regarding the severity of respiratory compromise at time of diagnosis and the subsequent morbid consequences. Methods This single-center, retrospective cohort study evaluated adults who received bleomycin treatment for Hodgkin lymphoma at Mayo Clinic in Rochester, Minnesota between January 2006 and August 2018. The primary objective was to characterize the respiratory severity at time of diagnosis in those admitted to the hospital with suspected pulmonary toxicity and PCP associated with bleomycin use. Degree of oxygenation was defined by the PaO 2 :FiO 2 (PF) ratio or SaO 2 :FiO 2 (SF) ratio when an arterial blood gas was not available. Bleomycin-associated pulmonary toxicity was defined by documentation of any clinical signs or symptoms of pulmonary impairment through electronic health record review. Diagnosis of PCP was established by polymerase chain reaction. Descriptive statistics were used to summarize the data. Results Among 376 patients receiving bleomycin-containing combination therapy for Hodgkin lymphoma, 134 (34%) had suspected bleomycin pulmonary toxicity, 14 (10%) of which had concomitant PCP. Of these, 38 (28%) required admission to the hospital. The median baseline PF (N=11) and SF (N=38) ratios at the time of diagnosis were 211 (102, 267) and 429 (325, 452), respectively. Presence of concomitant PCP was not associated with worse SF (429 v. 429, p=0.72). Most (60%) had appropriate oxygen saturations (>90%) on room air at presentation, while the remainder required immediate application of nasal cannula (37%) or closed face mask (3%). Eight patients required intensive care unit admission, 6 of which required mechanical ventilation for a median 4.5 (2.1, 11) days. The median ICU and hospital lengths of stay were 3.9 (1.4, 7.4) and 3.9 (2.7, 6.7) days, respectively. Four patients died in the hospital, all of whom required mechanical ventilation, but did not have concomitant PCP. Conclusions Nearly one-third of Hodgkin lymphoma patients with bleomycin-associated pulmonary toxicity required hospital admission for a median of 3.9 days. While the majority of patients did not require aggressive respiratory support, most patients who required mechanical ventilation died in hospital. Further investigations are needed to better understand the trajectory, treatment, and long-term implications of bleomycin pulmonary toxicity in Hodgkin lymphoma patients.