Search

In Tunisia, the ATRA era began in 1998 with the use, consecutively, of two regimens combining ATRA and an anthracycline with cytarabine (APL93), and without cytarabine (LPA99). From 2004, 51 patients with confirmed APL either by t(15;17) or PML/RARA were treated according to the PETHEMA LPA 99 trial. Forty three patients achieved CR (86%). The remaining seven patients had early death (one died before treatment onset): four caused by differentiation syndrome (DS) and three died from central nervous system hemorrhage. Multivariate analysis revealed that female gender (P=0.045), baseline WBC> 10 G/L ( P=0.041) and serum creatinine > 1.4mg/dl ( P=0.021) were predictive of mortality during induction. DS was observed in 16 patients (32%) after a median onset time of 15 days from treatment onset (range, 2-29). Body mass index ⩾ 30 (P=0.01) remained independent predictor of DS. Occurrence of hypertensive peaks significantly predicted occurrence of DS (P=0.011) and was significantly associated with high BMI (p=0.003). With a median follow-up of 50 months, 5 year cumulative incidence of relapse, event free and overall survival were 4.7%, 74% and 78%, respectively. [ABSTRACT FROM AUTHOR]

Severe sepsis defined as infection-induced organ dysfunction or hypoperfusion abnormalities predispose to septic shock and increased mortality in neutropenic setting. We aimed at determining predictors of severe sepsis in neutropenic patients. Between 1 October and 31 December 2007, 41 patients (21 with acute myeloid leukemia, 19 with acute lymphoid leukemia and one with autologous stem cell transplantation for a mantle cell lymphoma) with chemotherapy-induced neutropenia (<0·5 × 109/l) lasting for more than 7 days were included in this study. The median age was 28 years (range: 3–58 years). All patients were on oral antibacterial (colistin and gentamicin) and anti-fungal (amphotericin B) prophylaxis. The first neutropenic febrile episode was treated with piperacillin/tazobactam and colistin IV; if the patient remains febrile at 48 h from the start of this first line of treatment, amphotericin B i.v. is added. Imipenem was introduced in the case of non-response and finally glycopeptides were introduced according to the IDSA criteria. Severe sepsis and septic shock are defined according to the criteria of the consensus conference of the ACCP/SCCM excluding the leukocyte count since all the patients were neutropenic. Ninety-four febrile episodes were observed: 27 microbiologically documented (28·7%), six clinically documented (6·3%) and 61 fever of unknown origin (65%). Microbiologically documented infections were: 13 Gram-negative organisms, 11 Gram-positive organisms and three combined (Gram+ and -). Clinically documented infections were pneumonia (two), neutropenic enterocolitis (one), sinuses infection (one) and cutaneous infection (two). Severe sepsis accounted for 22 febrile episodes. Factors associated with the occurrence of severe sepsis were: hypophosphatemia (<0·8 mmol/l; p=0·05, OR=3·9, 95% CI: 1·3–45·7), hypoproteinemia (<62 g/l; p=0·006, OR=4·1, 95% CI: 1·4–11·4) and non-adapted antibiotherapy at the onset of severe sepsis (p=0·019, OR=2·7, 95% CI: 1·02–7·39). However, heart rate/systolic blood pressure ratio <1·1 (p<0·001, OR=0·1, 95% CI: 0·03–0·31) and Creactive protein <80 mg (p=0·001, OR=0·14, 95% CI: 0·04–0·54) were not predictive. [ABSTRACT FROM AUTHOR]

Background: The combination of all-trans-retinoic acid (ATRA) and chemotherapy has made acute promyelocytic leukemia (APL) a highly curable leukemia. However, several complications are reported with this treatment the most serious and life threatening being Retinoic Acid Syndrome (RAS). We aimed at identifying factors that could predict complications caused by ATRA during induction treatment of APL. Patients: Forty-two patients with confirmed 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 >10×109/L to prevent RAS in LPA 99. Results: Median age was 36 yr (7–64 yr), M/F=16/26 (0·61), median WBC was 2·4×109/L (range 0·6–100×109/L). WBC >10×109/L was noted in 14 patients (33%). Additional cytogenetic abnormalities were seen in 12/42 (28%). Median body mass index (BMI=weight/height2:N 20–25) was 24 kg/m2 (range 16–40 kg/m2), BMI >30 was noted in nine patients (8F and 1M). Thirty-three patients achieved CR (78·57%):18/24 (75%) in APL93 versus 15/18 (83%) in LPA99. Nine patients (21·42%) had early death. Causes of early death were: RAS (6) and CNS hemorrhage (3). Complications due to ATRA were: RAS (10), Scrotal ulcerations (3), Sweet syndrome (2), Perineal ulcerations (1), and 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 (p=0·83) were not predictive. Retinoic Acid Syndrome was more reported in patients with initial WBC >10×109/L (p=0·08). Conclusion: We found high BMI (>35) in female and treatment without Cytarabine to increase the risk of developing complications with ATRA. [ABSTRACT FROM AUTHOR]