Hela Ghedira

Risk factors of septic shock in patients with hematologic malignancies and Pseudomonas infections

Abstract Pseudomonas is a clinically significant and opportunist pathogen, usually associated in causing high mortality nosocomial infections. The aim of this study was to determine the risk factors associated with septic shock in patients diagnosed with hematologic malignancies and Pseudomonas infections. A total of 80 Pseudomonas isolates (77 Pseudomonas aeruginosa) were collected from 66 patients aged 2–64 years: 52 with acute leukemia (79%), 7 with lymphoma (10·5%), and 7 with other hematologic disorders (10·5%), between 2001 and 2009. The median age of the patients was 30 years. Isolates were collected mostly from bloodstreams (45%) and skin lesions (31·5%). The median time for microbiologic documentation was 8 days (range 0–35 days) from onset of neutropenia. At least 11 patients (16·6%) had recurrent (⩾2) infections. The clinical symptoms observed were skin lesions (34%), diarrhea (20%), isolated fever (18%), and respiratory symptoms (14%). The isolates tested were found resistant to piperacillin/tazobactam (43%), ceftazidime (31%), imipenem-cilastatin (26%), ciprofloxacin (25%), and amikacin (26%). Septic shock occurred in 16·2% of episodes (13/80). Crude mortality due to septic shock occurred in 19·6% of patients (13/66). The median time for response to antibiotic therapy in the remaining 80·4% of patients (53/66) was 2·5 days. Univariate analysis revealed that factors associated with septic shock were: fever for ⩾3 days in patients on antibiotic therapy (P = 0·019), serum lactate >5 mmol (P = 0·05), hemoglobin level <50 g/l (P = 0·042), hypoproteinemia <50 g/l (P = 0·01), procalcitonin >10 ng/ml (P = 0·031), and hypophosphatemia (P = 0·001). Multivariate analysis revealed that hypophosphatemia (P = 0·018), hypoproteinemia (P = 0·028), and high serum lactate (P = 0·012) are significant factors, independently associated with increased risk of septic shock in patients with hematologic malignancies and Pseudomonas infections.

Treatment of acute promyelocytic leukemia with PETHEMA LPA 99 protocol: a Tunisian single center experience

Abstract 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 × 109/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 × 109/L (range: 1·2 × 109–82·7 × 109/l). DS was severe in seven cases, moderate in four, and fatal in three cases. Body mass index ≥30 (P=0·044) and baseline WBC ≥20 × 109/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.

Recurrent differentiation syndrome or septic shock? Unresolved dilemma in a patient with acute promyelocytic leukemia

Differentiation syndrome (DS) is a life-threatening complication observed in patients with acute promyelocytic leukemia (APL) receiving induction therapy with all-trans-retinoic acid (ATRA). A bimodal incidence of DS has been observed, with a majority of cases occurring during the first week of ATRA treatment (“early” DS), but a substantial number of cases occurring during the third or even fourth week of ATRA treatment (“late” DS). However, to our knowledge occurrence of both early and late DS in the same patient has not been reported. We report an APL patient treated with the AIDA regimen, who experienced both early and late DS, a situation where differential diagnosis was difficult.

Molecular study of ABCB1 gene and its correlation with imatinib response in chronic myeloid leukemia

PurposeThe introduction and success of imatinib mesylate have become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, despite its high efficiency, resistance to imatinib has emerged as a significant problem, which may in part be caused by pharmacogenetic variability. Three single-nucleotide polymorphisms (C1236T, G2677T/A, C3435T) and/or mRNA expression changes of ABCB1 gene were demonstrated to be associated with inter-individual variability of imatinib response in CML patients. In this study, we aimed to examine whether genetic variations and/or altered expression of ABCB1 gene may influence response to imatinib.MethodsSixty nine CML Tunisian patients, undergoing imatinib therapy, were enrolled in this study. These were divided into two groups: responders and non-responders to imatinib. The relative transcript expression levels of ABCB1 gene and the distribution of allele and genotype frequency of ABCB1 SNPs were compared between these two categories of patients. Linkage disequilibrium tests and haplotypes analysis were also studied.ResultsOur results showed that the mRNA expression level of ABCB1 gene did not differ significantly between the two categories of patients. In addition, results obtained from ABCB1 polymorphisms study and their correlation with imatinib response showed that the optimal response rate to imatinib did not differ significantly between C1236T, G2677T/A or C3435T genotypes. However, haplotype analysis showed that the 1236C–2677A–3435C haplotype was observed only in imatinib non-responders’ patients suggesting that CAC haplotype was linked to higher risk of imatinib resistance.ConclusionFurthermore, analyses of ABCB1 haplotypes should be taken into account to study the relationship between ABCB1 genotypes and imatinib efficacy.

Factors associated with septic shock in patients with hematological malignancies and Pseudomonas infections

Background: Pseudomonas is a leading cause of nosocomial infections usually associated with high mortality. The aim of this study was to determine predictive factors of septic shock in patients with hematological malignancies and Pseudomonas infections. Methods: This study was conducted in a teaching hospital (Aziza Othmana University hospital, Tunis, Tunisia) to evaluate the clinical profile of infection due to Pseudomonas species and to determine risk factors for septic shock defined according to the criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Statistical analysis was performed with Pearson test.Level of significance was at p = 0.05. Results: Between 2001 and 2009 a total of 80 Pseudomonas isolates (77 P.aeruginosa) was collected in 66 patients: 52 with acute leukemia (79%),7 with lymphoma (10.5%), and 7 with other hematological disorders (10.5%). The median age was 30 years (range, 2—64years). Most common sites of the isolates were from bloodstroom (45%), and skin lesions (31.5%). Median time for microbiological documentation was 8 days (range, 0-35days) from onset of neutropenia. At least 12 patients (18.1%) had recurrent (≥2) infections due to Pseudomonas. The most common clinical signs observed were: skin lesions (34%), diarrhea (20%), isolated fever (18%), and respiratory symptoms (14%). Susceptibility to major anti-Pseudomonas antibiotics revealed that isolates tested were resistant to: piperacillin/tazobactam (43%), ceftazidim (31%), imipenemcilastatin (26%), ciprofloxacin (25%), and amikacin (26%). Septic shock occured in 16.2% of episodes (13/80). Crude mortality was (19.6%,13 of the 66 patients) all caused by septic shock. For the remaining 53 patients (79.4%) median time for response to antibiotherapy was 2.5 days. In univariate analysis, factors associated with septic shock were: fever lasting for more than 3 days in patients on antibiotherapy (p = 0.019), Creactive protein > 150 mg/l (p = 0.065), serum lactate > 5mmol (p = 0.05), hemoglobin level < 50 g/l (p = 0.042), hypoproteinemia < 50 g/l (p = 0.01), and procalcitonin >10ng/ml (p = 0.031). ts e251