Infliximab in chronic myelogenous leukemia.
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Biomedical subjects
Publications and source records attributed to Michel Leporrier.
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The prognostic value of fluorodeoxyglucose positron emission tomography (FDG-PET) and gallium-67 scan (GS) performed early after chemotherapy was assessed in 40 patients with newly diagnosed aggressive lymphoma. FDG-PET and GS were performed before and after three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or two cycles of ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone), with or without rituximab. Thirty-five patients had diffuse large B-cell lymphoma (DLBCL), two had mantle-cell lymphoma and three had T-cell lymphoma. Four patients relapsed despite early negative FDG-PET and GS including all three patients with T-cell lymphoma. Nine patients stayed in remission despite positive FDG-PET and/or GS of whom five showed moderate intensity residual bone uptake. Seven of these nine early false positives had a negative exam at the end of treatment. In patients with DLBCL, the 2-year event-free survival was 85% for negative versus 30% for positive FDG-PET patients (P = 0.003) whereas it was 78% for negative versus 33% for positive GS patients (P = 0.018). Sensitivity, specificity and diagnostic accuracy of FDG-PET and GS were not significantly different: 90% versus 70%, 76 versus 80% and 80 versus 77%, respectively. We conclude that both FDG-PET and GS are valuable tools to early predict outcome in patients with DLBCL.
BACKGROUND AND OBJECTIVES: In non-randomized studies, thalidomide appeared to be effective in myeloid metaplasia with myelofibrosis (MMM). We compared thalidomide to placebo for treatment of anemia in MMM. DESIGN AND METHODS: A prospective phase II B, randomized double-blind multicenter trial comparing thalidomide 400 mg/d with placebo for 180 days was conducted in 52 anemic patients (hemoglobin pounds Sterling 9 g/dL or transfused). The main outcome measure was a 2 g/L increase in hemoglobin or 20% reduction in transfusions. RESULTS: In the thalidomide group only 10 patients completed 6 months of treatment. At 180 days, in an intention-to-treat analysis, no difference was observed between the thalidomide and placebo groups as regards improvement of hemoglobin levels (one patient in each group) or reduction of red blood cell transfusions (three vs five patients, respectively). The spleen size, determined by ultrasonography, increased significantly less in the thalidomide group than in the placebo group (p < 0.05). Thalidomide had no apparent benefit on the Dupriez score, the severity score, survival, death, or any other clinical or biological parameter. Somnolence, gastro-intestinal signs, weight gain, and edema were significantly more frequent in the thalidomide group. Outpatient discontinuation of thalidomide was significantly correlated with a high severity score > 4 (odds ratio, OR = 16; p < 0.01), and g-glutamyl transferase levels > 40 IU/L (OR = 12; p < 0.05). INTERPRETATION AND CONCLUSIONS: Thalidomide (200-400 mg/d) does not demonstrate substantial efficacy in anemic MMM patients. The natural history of disease in the placebo group revealed spontaneous periods of remission of anemia. Tolerance of thalidomide was significantly correlated wih the severity and liver involvement of the disease.
The last years have yielded important new insights into the biological characteristics of chronic lymphocyte leukemia cells, which have lend to modify the diagnosis and prognosis criteria of the disease. The diagnosis is now based on morphology and immunophenotyping of blood lymphocytes, making the bone marrow examination unnecessary. However, detection of a clonal expansion of B-lymphocytes in the blood is far to be synonymous of leukemia, and even less an argument for starting a treatment. Prognosis classifications based on clinical and blood counts are now refined with genotyping and cytogenetics. These new tools should improved the therapeutic strategies in the next future.
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Fludarabine is a synthetic adenine nucleoside analog that is indicated for first- and second-line treatment of chronic lymphocytic leukemia (CLL). The recommended intravenous (i.v.) dosage regimen is 25 mg/m2 daily for 5 consecutive days, with treatment cycles repeated every 28 days. In treatment-naïve patients with Binet stage B and C CLL, i.v. fludarabine produces superior responses to established first-line chemotherapies. Fludarabine produces a higher overall remission rate (60-70%) and longer progression-free survival (median approximately 20-30 months) than standard therapy with chlorambucil+/-prednisone and CAP (cyclophosphamide/doxorubicin/prednisone), and a comparable overall remission rate to CHOP (cyclophosphamide/vincristine/prednisone/doxorubicin). Fludarabine demonstrates high efficacy in both intermediate-risk (Rai stage I or II) and high-risk (Rai stage III or IV) patients. Furthermore, fludarabine is equally effective in younger (< or =65 years) and older (>65 years) patients. Fludarabine has significant activity as monotherapy in previously treated CLL, producing objective response rates of up to 94% in typically small-scale, noncomparative studies, with the majority of studies yielding rates of 30-60%. In a phase III multicenter study, the overall remission rate was significantly higher with fludarabine than with CAP (48 versus 27%) among the subset of treatment-refractory patients (n=96). For those patients who are refractory to or have relapsed following conventional chemotherapy (chlorambucil, CAP and CHOP), fludarabine can be considered the treatment of choice for second-line therapy. Moreover, patients with relapsed CLL may benefit from retreatment with fludarabine if they have previously demonstrated sensitivity to the drug. Standard-dose i.v. fludarabine has an established safety profile and comparable tolerability to anthracycline-based regimens (CAP and CHOP) in terms of its myelosuppressive and immunosuppressive effects, and offers the advantage of a markedly lower incidence of gastrointestinal effects (nausea/vomiting) and alopecia.
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