High Body Mass Index (BMI) as a Predictor of Differentiation Syndrome (DS) In Acute Promyelocytic Leukemia (APL).

High BMI was recently identified as a new predictor of differentiation syndrome (DS) in a relatively small Tunisian series of 39 APL patients (pts) treated with ATRA and anthracycline based chemotherapy (Leuk Res 2010; 34: 545–547). We analyzed this parameter in a larger pt cohort included in European APL 93 and APL 2000 trials.

Between 1993 and 2006, 1196 APL patients (pts) were included in APL93 and 2000 trials, of whom 1016 APL had BMI determination (524/576 in APL 93 and 492/620 in APL 2000). In both trials, induction treatment consisted of ATRA and DNR + AraC except in one arm of APL 2000 trial where standard risk pts (ie low and int risk using Sanz score) received no AraC. Chemotherapy (CT) was started on day 1 of ATRA treatment in high risk (Sanz score) pts and on day 3 of ATRA treatment in standard risk pts except in one arm of APL 93 where standard risk pts received CT after ATRA. In APL 2000 (but not APL 93) trial, high risk patients received prophylactic dexamethasone from day 1 of ATRA.

Median age was 45 years (range: 1–80). 260 (25.6%) pts were high risk, 420 (41.3%) int risk and 336 (33%) low risk. Median BMI was 25.8 kg/m² (range: 10–38). CR was achieved in 92.9% pts. Overall incidence of DS (according to Frankel's criteria) was 23.3%. Prognostic factors associated with an increased risk of DS were baseline WBC > 3×10⁹/l (p=0.03) (best cut-off for WBC count), inclusion in APL2000 trial (p<0.0001) and randomization arm without AraC (p=0.028). When focusing on the low risk group, univariate analysis and multivariate analysis showed BMI > 25.5 (p=0.031) and inclusion in APL 2000 (p=0.002) to be significantly associated with occurrence of DS whereas age, sex, baseline WBC and absence of AraC had no prognostic impact. In low risk pts, occurrence of DS was associated with a trend for shorter survival (p=0.051). BMI however lost its prognostic value for DS in intermediate and high risk pts.

High BMI may be associated to a higher risk of DS, at least in low risk APL, suggesting that those patients may have to be monitored closely during induction treatment of APL.

Fenaux:CELGENE, JANSSEN CILAG, AMGEN, ROCHE, GSK, NOVARTIS, MERCK, CEPHALON: Honoraria, Research Funding.