Predictive Factors of All Trans-Retinoic Acid (ATRA) Related Complications during Induction Course of Acute Promyelocytic Leukemia (APL).

Background: The combination of ATRA and chemotherapy has made APL a highly curable leukemia. However several complications are reported with this treatement the most serious and life threatening being ATRA syndrome. We aimed at identifying factors that could predict complications caused by ATRA during induction treatement of APL.

Patients: 42 patients with comfirmed APL(by t(15,17) and/or PML/RARA) treated at our institution (University hospital of Tunis) between January 1998 and June 2006 using two consecutive protocols: European APL93 trial (24 patients) until February 2004 and Spanish PETHEMA LPA99 trial (18 patients) more recently. Induction regimen consisted of ATRA 45 mg/m²/d until CR combined to DNR 60 mg/m²/d×3 + Cytarabine 200 mg/m²/d×7 (APL93) and Idarubicin 12 mg/m² d2,4,6,8 (LPA99). Prednisone (0,5 mg/kg d1–d15) was added if WBC > 10 000/mm³ to prevent ATRA syndrome in LPA 99.

Results: Median age was 36 yr (7–64yr), M/F=16/26(0,61), median WBC was 2400/mm³(range 600–100 000/mm³). WBC>10 000/mm³ was noted in 14 patients (33%). Additional cytogenetic abnormalities were seen in 12/42(28%). Median Body Mass Index(BMI= weight/length²:N 20–25) was 24kg/m²(range 16–40kg/m²), BMI>30 was noted in 9 patients(8F and 1M).33 patients achieved CR (78,57%):18/24 (75%) in APL93 vs 15/18(83%) in LPA99.9 patients(21,42%) had early death. Causes of early death were:ATRA syndrome(6) and CNS haemorrhage (3). Complications due to ATRA were:ATRA syndrome(10), Scrotal ulcerations(3), Sweet syndrome(2), Perineal ulcerations(1), Pseudotumor cerebri (1). Prognostic factors for complications of ATRA(Fisher exact test) were:BMI>35 (p=0,055), induction treatment without cytarabine(LPA99 trial) (p=0,047), whereas age(p=0,74), gender (p=0,51), initial WBC (p=0,47), and additional cytogenetic abnormalities were not predictive. ATRA syndrome was more reported in patients with initial WBC>10 000 (p=0,08).

Conclusion: We found high BMI (>35) in female and treatement without Cytarabine to increase the risk of developping complications with ATRA.