Etoposide, ifosfamide, and methotrexate combination chemotherapy for aggressive non-Hodgkin's lymphomas after failure of the LNH 84 regimen.

We assessed the efficacy and tolerability of VIM (etoposide/ifosfamide/methotrexate) combination therapy in 24 patients who were failing the treatment protocol of the Lymphomes Non Hodgkiniens (LNH) 84 study. Eight patients were refractory to the LNH 84 induction cycles, but ten achieved a partial response (PR). The six remaining patients attained complete response (CR) after LNH 84 induction, but relapsed either during consolidation therapy or after completing the whole program. Twenty-three patients are evaluable for response. The VIM regimen provided a CR rate of 43% and a PR rate of 17%. Treatment failed in nine cases (39%). The CR rate was particularly high (67%) in the group of patients who had PR with LNH 84 induction treatment. Of the ten who had attained CR, five relapsed after 4 to 42 months and five are still alive with no evidence of disease after 29 to 62 months. VIM therapy was well tolerated. A total of 101 VIM courses were given. Myelotoxicity was the most common side effect. Grade 3 or 4 cytopenia was recorded after 11% of the cycles. Among eight infectious episodes recorded, one was fatal. This study demonstrates that CR and long disease-free survival are obtainable with the VIM regimen in a small number of patients failing a high-dose doxorubicin-containing first-line treatment.

[Hypothyroid hypertrophic myopathy following mantle irradiation for Hodgkin's disease. A case]. / Myopathie hypothyroïdienne hypertrophique après irradiation en mantelet pour maladie de Hodgkin. Une observation.

The authors report a case of hypothyroid hypertrophic myopathy consecutive to mantle irradiation for Hodgkin's disease. A rise in TSH level is frequent after mantle irradiation and it justifies prolonged monitoring of these patients' thyroid function, in view of the risk of patent hypothyroidism and perhaps cancer. The patient's age, the pre-irradiation lymphography and the chemotherapy associated with radiotherapy are all factors that influence the incidence of thyroid dysfunction, but there is no agreement concerning their relative importance. Hypertrophic myopathies due to hypothyroidism are rare, and their dramatic clinical presentation contrasts with an almost normal muscle histology. Alterations of energy metabolism and changes in the properties of myosin induced by hormonal deficiency account for the muscular weakness of these patients. On the other hand, the mechanism of muscle hypertrophy remains controverted, the most probable theory being and increase in the number of myotubes. Following irradiation, notably for Hodgkin's disease, the frequency of hypothyroidism requires a regular and systematic laboratory follow-up. Replacement therapy must be instituted if the basal TSH level increases, even if the T4 level is normal.

The number of CD34(+) cells in peripheral blood as a predictor of the CD34(+) yield in patients going to autologous stem cell transplantation.

The number of CD34(+) cells in peripheral blood (PB) is a guide to the optimal timing to harvest peripheral blood progenitor cells (PBPC). The objective was to determine the number of CD34(+) cells in PB that allows achieving a final apheresis product containing > or =1.5 x 10(6) CD34(+) cells/kg, performing up to three aphereses. Between March 1999 and August 2003, patients with hematological and solid malignancies who underwent leukapheresis for autologous bone marrow transplantation were prospectively evaluated. Seventy-two aphereses in 48 patients were performed (mean 1.45 per patient; range 1-3). PBPC were mobilized with cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (G-CSF) (n = 40), other chemotherapy drugs plus G-CSF (n = 7), or G-CSF alone (n = 1). We found a strong correlation between the CD34(+) cells count in peripheral blood and the CD34(+) cells yielded (r = 0.903; P < 0.0001). Using receiver-operating characteristic (ROC) curves, the minimum number of CD34(+) cells in PB to obtain > or =1.5 x 10(6)/kg in the first apheresis was 16.48 cells/microL (sensitivity 100%; specificity 95%). The best cut-off point necessary to obtain the same target in the final harvest was 15.48 cells/microL, performing up to three aphereses (sensitivity 89%; specificity 100%). In our experience, > or =15 CD34(+) cells/microL is the best predictor to begin the apheresis procedure. Based on this threshold level, it is possible to achieve at least 1.5 x 10(6)/kg CD34(+) cells in the graft with < or =3 collections.

Etoposide, ifosfamide and methotrexate combination chemotherapy in patients with aggressive non-Hodgkin's lymphoma after failure of the LNH 84 regimen.

We assessed the efficacy of an etoposide, ifosfamide and methotrexate combination therapy (VIM) in 24 patients failing the LNH 84 protocol. Eight of these patients were refractory to the LNH 84 induction regimen, 10 were partial responders and the six remaining attained complete response after LNH 84 induction but relapsed during consolidation therapy or after completing the whole programme. Twenty-three patients were evaluable for response. The VIM regimen provided a 43 per cent complete response rate and an additional 17 per cent partial response rate. The complete response rate was particularly high (67 per cent) in the group of patients who were partial responders to LNH 84 induction treatment. Of the 10 complete responders, five relapsed after 4 to 42 months and five are still alive with no evidence of disease after 27 to 60 months. Overall VIM was well tolerated. Myelotoxicity was the most common side-effect. Infections with fever were observed in 8 per cent of the VIM courses. This study demonstrates that a complete response and a long survival can be obtained in patients after failure of a high-dose doxorubicin containing front-line treatment.

Piperacillin and netilmicin combination therapy for febrile episodes in neutropenic patients.

We assessed the efficacy of a piperacillin (3 x 4 g/d) and netilmicin (5 mg/kg/d) combination therapy for infections in febrile neutropenic patients. The study was conducted over a 30-month period and 203 patients were included. Bone marrow transplant recipients were not included in this study. Origin of infection was documented in 101 (50%) episodes: 33 fungal, viral or parasitic infections and 68 bacterial infections mainly composed of septicemia. Of the 169 evaluable patients with proved bacterial infections or non-documented infections, 129 (76%) recovered with the piperacillin and netilmicin combination treatment. All gram-positive bacterial infections failing first line therapy were cured after the addition of vancomycin. Piperacillin and netilmicin appeared very effective in this large monocentric prospective study. It does not seem necessary to include vancomycin in first line therapy of infections of the neutropenic patients in our institution; however, vancomycin must be added early in the case of suspected or documented staphylococcal infection failing empiric treatment.