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Guy Leverger

Publications and source records attributed to Guy Leverger.

29 records · Page 2Linked to original sources
PubMed2003

Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials.

PURPOSE: To compare pediatric and adult therapeutic practices in the treatment of acute lymphoblastic leukemia (ALL) in adolescents. PATIENTS AND METHODS: From June 1993 to September 1994, 77 and 100 adolescents (15 to 20 years of age) were enrolled in the pediatric FRALLE-93 and adult LALA-94 protocols, respectively. Among the different prognostic factors, we retrospectively analyzed the effect of the trial on achieving complete remission (CR) and event-free survival (EFS). RESULTS: Patients were younger in the FRALLE-93 than in the LALA-94 protocol (median age, 15.9 v 17.9 years, respectively), but other characteristics were similar, including median WBC count (18 x 10(9) cells/L v 16 x 10(9) cells/L), B/T-lineage (54 of 23 v 72 of 28 patients), CD10-negative ALL (13% v 15%), and poor-risk cytogenetics (t(9;22), t(4;11), or hypodiploidy less than 45 chromosomes: 6% v 5%). The CR rate depended on WBC count (P =.005) and trial (94% v 83% in FRALLE-93 and LALA-94, respectively; P =.04). Univariate analysis showed that unfavorable prognostic factors for EFS were as follows: the trial (estimated 5-year EFS, 67% v 41% for FRALLE-93 and LALA-94, respectively; P <.0001), an increasing WBC count (P <.0001), poor-risk cytogenetics (P =.005), and T-lineage (P =.01). The trial and WBC count remained significant parameters for EFS in multivariate analysis (P <.0001 and P =.0004). Lineage subgroup analysis showed an advantage for the FRALLE-93 trial for CR achievement (98% v 81%; P =.002) and EFS (P =.0002) in B-lineage ALL and for EFS (P =.05) in T-lineage ALL. Age was not a significant prognostic factor in this population of adolescents. CONCLUSION: This study's findings indicate that adolescents should be included in intensive pediatric protocols and that new trials should be designed, inspired by pediatric protocols, for the treatment of young adults with ALL.

Adolescent↗
PubMed2003

Epidemiology and risk factors for gram-positive coccal infections in neutropenia: toward a more targeted antibiotic strategy.

The objective of this study was to evaluate the risk of acquiring gram-positive coccal infections in febrile neutropenic patients and to develop risk indexes for gram-positive and streptococcal infections. This prospective, multicenter study included 513 patients. The prevalence of gram-positive coccal infections was 21% (14% were staphylococcal infections and 7.8% were streptococcal infections). The mortality rate during the month after study enrollment was 5%. On multivariate analysis, the occurrence of gram-positive coccal infections was significantly associated with receipt of high-dose cytarabine therapy, proton pump inhibitors, and gut decontamination with colimycin without glycopeptides and presence of chills. Staphylococcal infection was significantly associated with use of nonabsorbable colimycin, and streptococcal infection was associated with diarrhea, use of nonabsorbable antifungals, receipt of high-dose cytarabine, and gut decontamination with colimycin. The relative risks for streptococcal infection were 2.9, 13.2, and 20.7 in the presence of 1, 2, and > or =3 parameters, respectively. Risk factors for staphylococcal and streptococcal infections differ among neutropenic patients. A simple scoring system for predicting streptococcal infection is proposed.

Anti-Bacterial Agents↗
PubMed2003

Economic evaluation of recombinant human granulocyte colony-stimulating factor in very high-risk childhood acute lymphoblastic leukemia.

PURPOSE: In a previous randomized study, the authors reported that granulocyte colony-stimulating factor (G-CSF) increased the chemotherapy dose-intensity delivered during the consolidation therapy of high-risk childhood acute lymphoblastic leukemia (ALL). The aim of the current study was to perform an economic evaluation in the same cohort. METHODS: In this open-label multicenter randomized trial, prophylactic G-CSF was administered after consolidation therapy courses. Economic data were retrospectively quantified for each patient: hospital stays, drugs, and blood products. RESULTS: Sixty-seven children were enrolled in the very high-risk branch of the FRALLE 93 protocol. Chemotherapy dose-intensity was significantly increased (105 +/- 5% in the G-CSF group vs. 91 +/- 4% in the non-G-CSF group, P < 0.001). The mean total costs per child were not statistically different: 32,309 dollars in the G-CSF group versus 31,569 dollars in the non-G-CSF group. Further analysis per child and per course (R3 or COPADM) demonstrated that the mean cost of hospitalization and the mean cost of intravenous antibiotics were significantly decreased in the G-CSF group after R3 courses (3,857 dollars vs. 4,993.80 dollars, P < 0.001; 171.40 dollars vs. 306.20 dollars, P = 0.029, respectively), but the cost of platelet transfusion was significantly increased (P = 0.03). Conversely, post-COPADM costs were similar. Finally, mean costs per course in the two randomized groups were not significantly different: 5,848.80 dollars versus 6,181 dollars and 7,388.10 dollars versus 6,475.70 dollars for R3 and COPADM, respectively. The 3-year probability of event-free survival between the two groups was not different. CONCLUSIONS: G-CSF can increase chemotherapy dose-intensity in very high-risk ALL without raising costs, but event-free survival was not improved. The cost benefit of prophylactic treatment by G-CSF relies on the chemotherapeutic regimen given prior to G-CSF administration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Family history of autoimmune thyroid disease and childhood acute leukemia.

The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.

Adolescent↗
PubMed2003

[Therapeutic progress in acute lymphoblastic leukemias and stage IV Burkitt-type lymphomas in children].

Prognosis of stage IV Burkitt's lymphoma according to Murphy's classification and FAB L3 acute lymphoblastic leukemia was dramatically improved during the two last decades through a very intensive and short duration chemotherapy. At the end of the seventies the rate of cure was 30% in stage IV Burkitt's lymphoma with up to 25% blasts in the bone marrow, and there was no cure for cases with central nervous system involvement and FAB L3 ALL. The French Society of Paediatric Oncology (SFOP) was one of the international leading groups in treatment research in these diseases. Successive LMB protocols led to the international LMB96 protocol involving France, United Kingdom and United States of America. Currently, event free survival of all stage IV Burkitt's lymphoma and FAB L3 LAL is higher than 85%, and approaches 80% in the cases with central nervous system involvement and 90% in the cases without CNS involvement. Relapse cases, occurring always early, still have a very bad prognosis and remain a challenge for the future.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

An investigation of the steady-state pharmacokinetics of oral valacyclovir in immunocompromised children.

Valacyclovir was administered to 28 immunocompromised children (ages 5-12 years) to obtain preliminary pharmacokinetic and safety information. Patients were randomized to valacyclovir regimens of 250 mg (9.4-13.3 mg/kg) or 500 mg (13.9-27.0 mg/kg) twice daily or 500 mg (13.2-21.7 mg/kg) 3 times a day. Acyclovir pharmacokinetics were evaluated at steady state. Valacyclovir was rapidly absorbed and converted to acyclovir. Mean (+/-SD) acyclovir peak concentrations from 250 mg and 500 mg valacyclovir were 4.11+/-1.41 and 5.19+/-1.96 microg/mL, respectively. Corresponding single dose area-under-curve values were 12.14+/-6.60 and 14.49+/-4.69h microg/mL. By using historical data for intravenous acyclovir as reference, the overall estimate of acyclovir bioavailability from valacyclovir was 48%, 2- to 4-fold greater than for oral acyclovir. In general, adverse events were not attributable to valacyclovir and were consistent with disease-related expectations and concomitant therapies. Dosage options for using valacyclovir in children are discussed.

Acyclovir↗
PubMed2002

Impact of addition of maintenance therapy to intensive induction and consolidation chemotherapy for childhood acute myeloblastic leukemia: results of a prospective randomized trial, LAME 89/91. Leucámie Aiqüe Myéloïde Enfant.

PURPOSE: To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 268 children with AML were registered in the Leucámie Aiquë Myéloïde Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME 89 pilot study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to receive or not receive MT. RESULTS: A total of 241 (90%) of 268 patients achieved a complete remission. The overall survival and event-free survival at 6 years were 60% +/- 6% and 48% +/- 6%, respectively. For the complete responders after consolidation therapy, the 5-year disease-free survival was not significantly different in MT-negative and in MT-positive randomized patients (respectively, 60% +/- 19% v 50% +/- 15%; P =.25), whereas the 5-year overall survival was significantly better in MT-negative randomized patients (81% +/- 13% v 58% +/- 15%; P =.04) due to a higher salvage rate after relapse. CONCLUSION: More than 50% of patients can be cured of AML in childhood. Either drug intensity or each of the induction and postremission phases may have contributed to the outstanding improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose MT may contribute to clinical drug resistance and treatment failure in patients who experience relapse.

Amsacrine↗
PubMed2002

A white blood cell index as the main prognostic factor in t(8;21) acute myeloid leukemia (AML): a survey of 161 cases from the French AML Intergroup.

While the t(8;21) translocation is one of the most recurrent chromosomal abnormalities in acute myeloid leukemia, prognostic studies have been hampered by the relatively few number of patients reported. We thus performed a large retrospective study in 161 adults and children with t(8;21) acute myeloid leukemia, all prospectively enrolled in 6 different trials conducted in France between 1987 and 1998 (median follow-up 4.9 years). Prognostic studies were performed in the 154 patients who achieved a complete remission. Individual data were registered, including sex, age, blood and marrow counts, extramedullary disease, and cytogenetics. The value of allogeneic stem cell transplantation versus chemotherapy as postremission therapy was evaluated according to the intent-to-treat principle. Estimated 5-year disease-free survival (DFS) and overall survival were 52% and 59%, respectively. Outcome was not significantly better in patients from the stem cell transplantation group (estimated 5-year DFS and survival, 56% vs 52% and 67% vs 57%; P =.55 and.64, respectively). White blood cell count (WBC) was the only identified prognostic factor. To further take into account the spontaneous differentiation potential of the leukemic clone, a WBC index was derived as the product of WBC by the ratio of marrow blast. This WBC index was a more powerful factor than the original WBC, allowing us to distinguish 3 subgroups of patients with different outcomes (low index, < 2.5; intermediate index, 2.5-20; high index, 20 or more). In multivariate analysis, the WBC index was the only prognostic factor for DFS (P =.003), complete remission duration (P =.002), and overall survival (P =.04).

Acute Disease↗
PubMed2002

Interaction between methotrexate and ciprofloxacin.

High-dose methotrexate is used in malignant hemopathies and solid tumors in children. Methotrexate serum concentrations must be monitored because of the possible toxicity of drug elimination delay. Several drugs (e.g., penicillin, probenecid) can alter the elimination of methotrexate. The authors report two cases of delayed elimination of methotrexate in patients receiving ciprofloxacin, with severe toxicity.

Adolescent↗
PubMedDate not supplied

[Paediatric specificity of antifungals use].

Specificity of antifungals use in paediatric patients is linked to mycoses epidemiology in this population. Pharmacokinetics vary with patient age. Although studies are in progress, pharmacokinetic data in children are limited in number for most antifungals. Among antifungal agents, those approved in France for use in children are rare. Adverse event frequency can differ in children, as compared to frequency in adults, and drug interaction should be a major worry. Relative interest and cost of available forms in the paediatric population in not always taken into account. For each different situation, an optimal strategy of antifungals use in children should be determined.

Antifungal Agents↗