Outcomes for newly diagnosed patients with acute myeloid leukemia dosed on actual or adjusted body weight

Abstract

Purpose Data from solid tumor malignancies suggest that actual body weight (ABW) dosing improves overall outcomes. There is the potential to compromise efficacy when chemotherapy dosages are reduced, but the impact of dose adjustment on clinical response and toxicity in hematologic malignancies is unknown. The purpose of this study was to evaluate the outcomes of utilizing a percent of ABW for acute myeloid leukemia (AML) induction chemotherapy dosing. Methods This retrospective, single-center study included 146 patients who received 7 + 3 induction (cytarabine and anthracycline) for treatment of AML. Study design evaluated the relationship between percentage of ABW dosing and complete response (CR) rates in patients newly diagnosed with AML. Results Percentage of ABW dosing did not influence CR rates in patients undergoing induction chemotherapy for AML (p = 0.83); nor did it influence rate of death at 30 days or relapse at 6 months (p = 0.94). When comparing patients dosed at 90–100 % of ABW compared to <90 % ABW, CR rates were not significantly different in patients classified as poor risk (p = 0.907). All favorable risk category patients obtained CR. Conclusions Preemptive dose reductions for obesity did not influence CR rates for patients with AML undergoing induction chemotherapy and did not influence the composite endpoint of death at 30 days or disease relapse at 6 months.

Effects of chemotherapy dose reductions in overweight patients with acute myeloid leukaemia: A Danish nationwide cohort study

“…Crysandt et al and Cahu et al 33,34 retrospectively analysed data from the prospective clinical trials AML2003 and GOELAMS 2001 including younger adults (≤60 years) with higher proportions of favourable cytogenetic risk, and found either a univariate association to inferior survival 33 or a trend towards inferior survival but no differences in event‐free survival 34 . Other studies included older patients (>60 years) mostly from single institution experiences have not been able to associate DR or dose capping to inferior survival 35–39 . However, none of the afore‐mentioned studies adjust for known powerful covariates.…”

“…31,32 Several other studies have assessed this question and the results are conflicting; where some find a negative survival effect of DR or dose capping, 33,34 others find no effect or better outcomes in overweight receiving DR or dose capping. [35][36][37][38][39] Notable differences between studies are study population, cytogenetic risk, and age. Crysandt et al and Cahu et al 33,34 retrospectively analysed data from the prospective clinical trials AML2003 and GOELAMS 2001 including younger adults (≤60 years) with higher proportions of favourable cytogenetic risk, and found either a univariate association to inferior survival 33 or a trend towards inferior survival but no differences in event-free survival.…”

“…Several other studies have assessed this question and the results are conflicting; where some find a negative survival effect of DR or dose capping, 33,34 others find no effect or better outcomes in overweight receiving DR or dose capping 35–39 . Notable differences between studies are study population, cytogenetic risk, and age.…”

“… 34 Other studies included older patients (>60 years) mostly from single institution experiences have not been able to associate DR or dose capping to inferior survival. 35 , 36 , 37 , 38 , 39 However, none of the afore‐mentioned studies adjust for known powerful covariates. We acknowledge that the present study cannot provide the optimal dosing strategy within the narrow therapeutic index of chemotherapy, and it is likely that further reductions, that is, 75% of full BSA‐based doses may impact outcomes more profoundly.…”

Complex karyotype including ring chromosome 11 in a patient with acute myeloid leukemia: case report

“…Recent studies have suggested that obesity is a risk factor associated with AML. [1][2][3] Classically, karyotyping has formed a powerful independent prognostic indicator in this group of diseases. 4,5 It serves to identify biologically distinct subsets of disease and has been widely used to provide the framework for risk-adapted treatment approaches.…”