Outcomes in obese and overweight acute myeloid leukemia patients receiving chemotherapy dosed according to actual body weight

Abstract

Cytotoxic chemotherapy dosages are traditionally calculated according to body surface area (BSA). No guidelines exist for chemotherapy dosing of acute myeloid leukemia (AML) patients at extremes of weight. We investigated the efficacy and safety of chemotherapy dosed according to BSA based on actual body weight (ABW) among under/normal weight, overweight, and obese AML patients. AML patients (excluding acute promyelocytic leukemia) treated with anthracycline and cytarabine-based remission induction chemotherapy from 2002 to 2009 at Cleveland Clinic were divided into three body mass index (BMI) groups: under/normal weight (BMI 24.9), overweight (BMI 25.0-29.9), and obese (BMI 30.0). Among 247 AML patients, 81 (33%) were under/normal weight, 81 (33%) were overweight, and 85 (34%) were obese. Complete remission (CR) rates were similar among these groups (69.1, 79.0, and 76.5%, respectively; P 5 0.321), as was median survival (10.7, 16.7, and 14.2 months, respectively, P 5 0.352) and 30-day mortality (3.7, 2.5, 7.1%, respectively, P 5 0.331). There was no difference among groups in days to neutrophil or platelet recovery, hospitalization days for induction chemotherapy, and bacteremia. After adjustment for confounders (age, sex, BMI, white blood cells, cytogenetic risk, etiology, and bacteremia), overall survival was significantly shorter for normal weight compared to overweight (P 5 0.006) and obese (0.038) patients. Response rates and adverse events were not significantly different among AML patients of all weight classes when induction chemotherapy was dosed according to ABW. Induction chemotherapy in these patients can be safely dosed using ABW. Am. J.

Association of body mass index and survival in pediatric leukemia: a meta-analysis

“…Data from preclinical (36) and limited clinical settings (37,38) suggest pharmacokinetic variation in the metabolism of common chemotherapy agents in the obese, yet prospective trials have found no such differences by BMI (9) or in those dosed with actual compared with ideal body weight (39)(40)(41). Other hypotheses focus on the effects of obesity on both the leukemia microenvironment and the host.…”

Prognosis of body mass index and chemotherapy dose capping in acute myeloid leukaemia

“…In AML, a first study addressing this question included 21 obese patients, and those who received a dose adjustment had a lower CR rate, while toxicity did not differ between patients [6]. Finally, a recent study revealed that outcomes and toxicities in AML patients treated with ABW based chemotherapy doses did not differ according to BMI [14].…”

Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia: results from NOPHO-AML 2004

“…In contrast, we surprisingly found a trend for being overweight at diagnosis being associated with superior outcome in children aged 10-17 years [unrelated to t(8;21) status], similar to what has been reported in adults with AML. [40][41][42] The effect of being overweight in the oldest children with AML may be more similar to the effect of being overweight in adults. In addition, the overweight group may have benefitted from the therapy without dose reductions.…”