Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols

Abstract

We investigated whether body mass index (BMI) correlates with distinct outcomes in newly diagnosed acute promyelocytic leukemia (APL). The study population included 144 patients with newly diagnosed and genetically confirmed APL consecutively treated at a single institution. All patients received All-trans retinoic acid and idarubicin according to the GIMEMA protocols AIDA-0493 and AIDA-2000. Outcome estimates according to the BMI were carried out together with multivariable analysis for the risk of relapse and differentiation syndrome. Fifty-four (37.5%) were under/ normal weight (BMI < 25), whereas 90 (62.5%) patients were overweight/obese (BMI > 25). An increased BMI was associated with older age (P < .0001) and male sex (P ‫؍‬ .02). BMI was the most powerful predictor of differentiation syndrome in multivariable analysis (odds ratio ‫؍‬ 7.24; 95% CI, 1.50-34; P ‫؍‬ .014). After a median follow-up of 6 years, the estimated cumulative incidence of relapse at 5 years was 31.6% (95% CI, 22.7%-43.8%) in overweight/obese and 11.2% (95% CI, 5.3%-23.8%) in underweight/normal weight patients (P ‫؍‬ .029). Multivariable analysis showed that BMI was an independent predictor of relapse (hazard ratio ‫؍‬ 2.45, 95% CI, 1.00-5.99, in overweight/obese vs under/normal weight patients, P ‫؍‬ .049). An increased BMI at diagnosis is associated with a higher risk of developing differentiation syndrome and disease relapse in APL patients treated with AIDA protocols. (Blood. 2012;119(1):49-54) IntroductionObesity has received considerable attention in the medical community because of its negative impact on human health. More recently, excess of body weight has been associated with an increased risk of a wide range of malignancies. [1][2][3] In a meta-analysis of cohort studies, Larsson and Wolk reported epidemiologic evidence suggesting that an excess of body weight is a risk factor for several hematologic cancers, including leukemia, non-Hodgkin lymphoma, and multiple myeloma. 4 In particular, compared with nonoverweight persons, the relative risk of leukemia for overweight and obese persons was reported to be 1.14 and 1.39, respectively, whereas a 5-kg/m 2 increase in body mass index (BMI) was associated with a 13% increased risk of leukemia. 4 As to the impact of BMI on treatment response and outcome, a number of studies have shown that obesity is associated with a poorer overall survival and disease-free survival in patients with breast cancer. 5,6 By contrast, the correlation between BMI and treatment outcome has not yet been investigated in patients with leukemia.Acute promyelocytic leukemia (APL), once known as the most rapidly fatal leukemia subtype, is nowadays considered the most frequently curable acute leukemia of adults. 7 Indeed, modern combined approaches with all-trans retinoic acid and anthracycline chemotherapy yield complete remission rates greater than 90% and long-term cure rates of 70% to 75%. [8][9][10][11] Disease relapse and death during induction because of hemorrhage, infection, or differentiation syndro...

Effect of body mass index on the outcome of children with acute myeloid leukemia

“…19 The results of a recently published study of children and adults with APL showed that overweight/obese patients had a significantly higher relapse rate and incidence of differentiation syndrome. 20 These results may suggest a relationship between obesity-related metabolic mediators and the pathogenesis of APL.…”

Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia

“…The adverse impact of obesity beginning at time of diagnosis on EFS and disease-related mortality has been demonstrated across multiple studies in pediatric ALL, [2][3][4][5]28 adult ALL, 39 and other hematologic malignancies. [40][41][42] The newly identified effect of obesity to increase risk for persistent MRD raises the question of whether obese patients should be considered as a higher risk group from time of diagnosis, analogous to adolescents, who could potentially benefit from more intensive therapy during induction. Alternatively, and in contrast to immutable host and leukemia risk factors, the added risk from obesity may be modifiable and amenable to intervention as suggested in CCG1961 in which normalization of BMI mitigated the adverse impact on EFS.…”

Introducing biological features at diagnosis improves the relapse risk stratification in patients with acute promyelocytic leukemia treated with ATRA and chemotherapy

“…With regard to the impact of the PML/RARA transcript, several studies [3,6,13,14] have previously reported a trend toward an inferior outcome for BCR3 isoform. On a more mature follow-up, we previously found [15] that patients with BCR3 transcript had a significantly higher relapse rate. A long-term follow-up analysis of our patient series also revealed that FLT3-ITD confers poor prognosis, with a 9 years OS of 96% in the FLT3-ITD2ve cohort compared to 39% in the FLT3-ITD1ve cohort and 9-year CIR rates of 4% and 60% for the FLT32ve and FLT31ve cohorts, respectively [12].…”