Impact Of Renal Insufficiency and Obesity On Safety and Outcomes Of BEAM Conditioning

BEAM (carmustine, etoposide, cytarabine and melphalan) is a standard conditioning regimen for patients with NHL undergoing autotransplant. Guidelines do not address whether patients with marginal renal function or obesity should undergo dose-adjustment to limit toxicity, and practices vary among centers.

We reviewed all patients who had BEAM autotransplant at MSKCC, 9/2003 - 12/2011; none received dose adjustment for chronic renal insufficiency [CRI, creatinine clearance (CrCl) 29-59 ml/min] or obesity (BMI>30). Outcomes included OS, relapse risk, transplant length of stay (LOS), and incidence of toxicities including mucositis, febrile neutropenia, and organ damage (acute renal failure by AKIN criteria; pulmonary toxicity requiring oxygen or corticosteroids; heart failure requiring inotropic support). Uni- and multivariate analysis evaluated association with baseline renal function and BMI, as well as age, histology, prior therapy, disease response, and comorbidity (hematopoietic stem cell transplant comorbidity index ≥4). Logistic regression was used for toxicity endpoints; linear regression and ANOVA were used for LOS; and Cox regression model and Gray’s competing risks were used for OS and relapse risk.

343 patients received BEAM during the study period; median (range) age=56 (17-73), estimated CrCl=92 (29-208), and BMI=27.6 (16-47). 12% had CRI and 33% were obese (12% BMI≥35, 3% BMI≥40). Stepwise multivariate analysis showed CRI (OR 2.9, P<0.01) and obesity (OR 2.5, P<0.01) were associated with risk of organ damage independent of comorbidity and histology. Mucositis and febrile neutropenia were not associated with CRI or obesity. CRI (P=0.03), but not obesity, was associated with longer LOS. Relapse risk was associated with histology (PTCL vs. DLBCL, HR 2.3, P=0.01) and response at transplant (PR vs. CR, HR 2.3, P<0.01), but not CRI or obesity. Obesity was not clearly associated with overall survival (HR 0.62, P=0.10, NS), but CRI was associated with worse overall survival (HR 2.2, P<0.01) independent of disease status (for PR, HR=2.0, P=0.01), histology, prior therapy, or comorbidity (P=NS). However, 100d mortality was uncommon in patients with preserved (6/303, 2%) or impaired (2/40, 5%) renal function (P=NS).

Patients with CRI or obesity experience increased risks of acute organ damage, and those with CRI have inferior OS, but 100d mortality remains low in both groups. Our findings do not support routine dose-modification of BEAM for obesity or moderate renal insufficiency.

No relevant conflicts of interest to declare.