[A case of de novo acute basophilic leukaemia: diagnostic criteria and review of the literature]. / A propos d'un cas de leucémie à basophiles de novo: critères diagnostiques et revue de la littérature.

We report a case of a de novo acute basophilic leukaemia, revealed by an infectious pneumopathy in a 73 year old man. The full blood count revealed an hyperleucocytosis associated with an unregenerative normocytic normochrom anaemia and a thrombocytopenia. The blood and bone marrow smears showed a mixture of undifferentiated blast cells and basophiloblasts (high nucleo-cytoplasmic ratio, coarse basophilic cytoplasmic granules), along with basophilic precursors and basophilic polymorphonuclears. All the blasts were MPO negative but positive for the toluidine blue metachromatic coloration, which is considered as consistent with basophilic lineage. Immunophenotypic studies showed myeloid blasts, without maturity marker, CD 117 negative and CD203 cytoplasmic positive, the latter known to be highly representative of the basophilic lineage. This very clear-cut phenotype, associated with the morphology of cells, were arguments to ascertain the basophilic lineage of the blasts without the need of electron microscopic study. Cytogenetic and RNA analysis revealed the presence of a Philadelphia chromosome and of a BCR-ABL transcript with the unusual junction e6a2. Thus, imatinib was added to the conventional chimiotherapy and the patient is currently in complete remission. This clinical prompted allows us to review the literature on acute basophilic leukaemia and to state on the different diagnostic criteria of this rare disorder.

Granulocyte colony-stimulating factor after intensive consolidation chemotherapy in acute myeloid leukemia: results of a randomized trial of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques.

PURPOSE: Ten years after the first clinical studies, the clinical impact of myeloid growth factors in acute myeloid leukemia is still unclear. One of the objectives of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques (GOELAM) 2 trial was to evaluate the benefit of granulocyte colony-stimulating factor (GCSF) given only after the two courses of intensive consolidation chemotherapy (ICC) used to maintain complete remission (CR). PATIENTS AND METHODS: One hundred ninety-four patients who were in CR after induction treatment were randomly assigned to receive G-CSF (100 patients) or no G-CSF (94 patients) after two courses of ICC (ICC 1, high-dose cytarabine plus mitoxantrone; ICC 2, amsacrine plus etoposide). G-CSF (filgrastim) was administered from the day after chemotherapy until granulocyte recovery at a daily dose of 5 microg/kg. RESULTS: In the G-CSF group, the median duration of neutropenia (< 0.5 x 10(9)/L) was dramatically reduced, both after ICC 1 (12 v 19 days, P <.001) and after ICC 2 (20 v 28 days, P <.001). The median duration of hospitalization was also significantly shorter in the G-CSF group (24 v 27 days after ICC 1, P <.001; 29 v 34 days after ICC 2, P <. 001). The median duration of intravenous antibiotics was significantly reduced after ICC 1 and ICC 2, and the median duration of antifungal therapy was significantly reduced after ICC 1. However, the incidence of microbiologically documented infections, the toxic death rate, the 2-year disease-free survival, and the 2-year overall survival were not affected by G-CSF administration. Moreover, the median interval between ICC1 and ICC2 was reduced by only 2 days, and the number of patients undergoing ICC2 was not increased in the G-CSF arm. CONCLUSION: G-CSF should be administered routinely after ICC to reduce the duration of neutropenia and hospitalization. However, G-CSF did not seem to significantly increase the feasibility of this two-course program or modify overall outcome.

[Methotrexate pneumonitis arising during the treatment of non-Hodgkin's lymphomas with the m-BACOD protocol]. / Pneumopathies du méthotrexate survenant dans le cadre du traitement des lymphomes non hodgkiniens par le protocole m-BACOD.

We retrospectively studied 32 patients treated with the m-BACOD regimen in a single institution between January 1988 and December 1991. After four to seven courses, four patients presented severe acute pneumonitis (PaO2 < 55 mmHg in room air), with diffuse bilateral interstitial syndrome. Broncho-alveolar lavage displayed increased lymphocyte count (> 45%) with inversion of CD4/CD8 in two cases and no evidence of parasitic, bacterial or viral infection. All patients received methyl-prednisolone (0.5 to 1 mg/kg/d x 1 week) with both complete clinical and radiological recovery within a week. The m-BACOD regimen was continued without bleomycine for four patients and without bleomycine plus methotrexate for two patients, until the completion of eight courses, without recurrence of pneumonitis. Drug-exclusion decisions were made empirically because the exact nature of the pneumonitis was not recognized at the time of diagnostic. Because of the regular administration in the m-BACOD regimen, methotrexate leads to an increased risk of pneumonitis. We concluded that the use of the m-BACOD regimen should henceforth be discontinued.

Pygidial secretions ofPasimachus subsulcatus (Coleoptera: Carabidae) deter predation byEumeces inexpectatus (Squamata: Scincidae).

The carabid beetlePasimachus subsulcatus is an abundant ground-dwelling insect in west central Florida that exudes a powerful mucous membrane irritant when disturbed. This secretion can be sprayed over 10 cm from the abdominal tip. The southeastern five-lined skink,Eumeces inexpectatus, is an abundant insectivorous lizard sympatric withPasimachus. We assessed the availability ofPasimachus toEumeces and found it to be within the foraging microenvironment of the lizard. Analysis ofEumeces gut contents and field feeding trials indicate thatPasimachus are not ingested by the lizard, yet arthropods of comparable size and exoskeletal thickness are ingested. The movement response ofEumeces to isolatedPasimachus secretion constituents, conducted in a modified Y-maze laboratory experiment, was used to assess the repellent capabilities of the secretion.Eumeces are consistently repelled byPasimachus secretion constituents, indicating that the beetle is protected chemically from the lizard.

Defensive secretion of the carabid beetlePasimachus subsulcatus.

The defensive secretion of the carabid beetlePasimachus subsulcatus is a concentrated solution (up to 90%) of carboxylic acids, amounting to about 1% of body mass. It contains three major components (methacrylic, tiglic, and angelic acids) and four minor components (isobutyric, 2-methyl-butyric, isovaleric, and senecioic acids). In the single population of this large flightless beetle that was examined, the relative ratio of acidic components was remarkably constant from individual to individual.

[Practical use of cefepime in an University hospital. Retrospective study of 35 cases]. / Utilisation pratique du céfépime dans un CHU. Etude rétrospective de 35 cas.

The authors report a retrospective study of 35 patients treated with cefepime (Axepim). This patients were either hospitalized in a medical or in a surgical ICU or were febrile neutropenic patients. The non neutropenic group was put on cefepime for nosocomial pneumonia or miscellaneous sepsis. When recovered, Enterobacteriaceae were the most frequent pathogens. Clinical cure rate for the patients treated with cefepime was 83%. Cefepime is a safe and effective empirical treatment for serious infections and nosocomial infections in particular.

Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study.

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor-risk ALs.

A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).

The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 micrograms/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients >/=65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted.