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Acute promyelocytic leukemia (APL) has now become the most curable of all subtypes of acute myeloid leukemia. A cure rate of 75-80% can be anticipated with a combination of all-trans retinoic acid (ATRA) and anthracyclines. In Tunisia, the ATRA era began in 1998 with the use, consecutively, of two regimens of a combination of ATRA with anthracycline and cytarabine (APL93), and without cytarabine (LPA99). From 2004, 39 patients with confirmed APL either by t(15;17) or PML/RARA were treated by the PETHEMA LPA 99 trial. The rationale of this protocol by avoiding cytarabine is to reduce death in complete remission (CR) without increasing the incidence of relapse. Thirty-three patients achieved CR (84.6%). The remaining six patients were considered as failure due to early death: three caused by differentiation syndrome (DS) and three died from central nervous system hemorrhage. Baseline blood cell count (WBC) >10 x 10(9)/l (P=0.26) and creatinine >1.4 mg/dl (P=0.42) were not predictive of mortality. DS was observed in 11 patients (30.5%) with a median onset time of 12 days (range: 3-23 days) and median WBC of 29 x 10(9)/L (range: 1.2 x 10(9)-82.7 x 10(9)/l). DS was severe in seven cases, moderate in four, and fatal in three cases. Body mass index > or =30 (P=0.044) and baseline WBC > or =20 x 10(9)/l (P=0.025) are independent predictors of DS. The median follow-up of this study is 36 months. Thirty patients are alive in continuous complete remission; two patients died in CR from septic shock and secondary myelodysplastic syndrome respectively; one patient died 47 months after achieving two relapses. Event free survival from diagnosis was 80% and overall survival was 82%. Our results are quite acceptable and can be improved by reducing mortality rate.

Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January-December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram-negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate17 mmol/l (OR = 68, p0.001) and serum lactate3 mmol/l (OR = 62, p0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p0.001) and serum bicarbonate17 mmol/l (OR = 61, p0.001). In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (3 mmol/l) and low serum bicarbonate (17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients.

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.