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Biomedical subjects

E de Campos

Publications and source records attributed to E de Campos.

5 recordsLinked to original sources

A single-blind, randomised, vehicle-controlled dose-finding study of recombinant human granulocyte colony-stimulating factor (lenograstim) in patients undergoing chemotherapy for solid cancers and lymphoma.

This study evaluated the effect of glycosylated recombinant human granulocyte colony-stimulating factor (rHuG-CSF; lenograstim) on neutrophil granulocyte counts and on cells of other haematopoietic lineages in 66 patients with solid cancer or lymphoma who received myelosuppressive chemotherapy. Beginning 1 day after completion of chemotherapy, patients received lenograstim (at dosages of 0.5, 2, 5 or 10 micrograms/kg) or vehicle subcutaneously once daily for 14 consecutive days. Compared with vehicle, lenograstim significantly accelerated neutrophil recovery after chemotherapy in a dose-dependent manner. Mean neutrophil counts recovered to > 1.0 x 10(9) cells/l by day 13 in the vehicle group compared with days 11, 10, 8 and 7 in the 0.5, 2, 5 and 10 micrograms/kg lenograstim groups, respectively. Doses of 0.5 and 2 micrograms/kg of lenograstim had a significant effect on the duration of neutropenia (< 1.0 x 10(9) cells/l), the area under the absolute neutrophil count (ANC) curve and the time to ANC nadir. The dose of 5 micrograms/kg additionally decreased the total area of neutropenia and gave the narrowest range of values for all neutrophil parameters, while the 10 micrograms/kg dose brought no added benefit. A dose-response effect of lenograstim on time to neutrophil recovery was observed both for patients who received chemotherapy on a single day (n = 35) and for those who received chemotherapy over several days (n = 29). Based on these findings, a dose of 5 micrograms/kg/day was chosen for further trials.

Adjuvants, Immunologic↗

Clinical and in vitro effects of recombinant human erythropoietin in patients receiving intensive chemotherapy for small-cell lung cancer.

PURPOSE: Recombinant human erythropoietin (r-Hu-EPO) is known to be effective in untreated cancer patients. Here we assess the possibility that r-Hu-EPO may also prevent or reduce anemia in patients who receive cytotoxic chemotherapy. METHODS: Thirty-six patients with small-cell lung carcinoma (SCLC) were enrolled onto a three-arm, randomized trial to investigate the effect of r-Hu-EPO on hemoglobin (Hb) levels and RBC and platelet (Plt) transfusions during chemotherapy. Bone marrow progenitors were studied before and after treatment. Two groups of patients received r-Hu-EPO at a dose of either 150 IU/kg (group 150) or 300 IU/kg (group 300) three times per week for the duration of chemotherapy. A control group did not receive r-Hu-EPO (group O). A maximum of six cycles of a chemotherapy regimen that consisted of vincristine, ifosfamide, carboplatin, and etoposide (VICE) were given to all patients. Hematologic parameters were measured weekly, and RBC or Plt transfusions were given for Hb levels less than 9 g/dL and Plt counts less than 20 x 10(9)/L. RESULTS: Hb levels decreased in all patients, but onset of anemia was delayed in groups that received r-Hu-EPO (P = .002). A total of 116 U RBC were transfused in group 0, 54 in group 150, and 52 in group 300 (P = .017). In addition, there was a nonsignificant trend toward higher Plt counts and fewer Plt transfusions in patients who received r-Hu-EPO. CONCLUSION: r-Hu-EPO at a dose of either 150 or 300 IU/kg three times weekly delays the onset of anemia and reduces RBC transfusion requirements in patients who undergo intensive chemotherapy for SCLC. A possible effect of r-Hu-EPO on platelet numbers deserves further study.

Adult↗

Haemopoietic progenitor and myeloid cell kinetics in humans treated with interleukin-3 and granulocyte/macrophage colony-stimulating factor in combination.

Patients with advanced adenocarcinoma of the colon, rectum or pancreas were entered into trials for evaluation of treatment with sequential doses of IL-3 and GM-CSF. They received 0.25 to 5 micrograms IL-3/kg/d for up to 7 days, followed by 1 microgram GM-CSF/kg/day for a maximum of 10 further days. We assessed the kinetics of bone-marrow cell proliferation and of blood production using tritiated thymidine labelling in vitro and in vivo. Megakaryocytic-CFC were unaffected but proliferation rates of GM-CFC and BFU-E were increased. Progenitor cells were mobilized (12-fold over baseline) into the peripheral blood. The proliferative activity of maturing cells in the marrow was increased (cell-cycle times were reduced by at least 30%). This translated into amplified blood cell production (WCC approximately 30 x 10(9)/l), a 2.2-fold increase in platelet counts and significant eosinophilia. Newly generated neutrophils appeared in the circulation at the normal time and their peripheral half-life was also normal. The calculated 3.2-fold amplification in neutrophil production required nearly 2 extra divisions in the marrow, shared between the progenitors and the proliferating granulocytic cells. The results were compared with those of a previous trial using GM-CSF only, although at a 10-fold higher dose level. Comparable levels of peripheral neutrophils were obtained in both trials but significant ineffective granulopoiesis developed in the earlier study. This was overcome in the present study, the priming dose of IL-3 apparently giving the latitude to utilize lower doses of GM-CSF with less risk of complications.

Adenocarcinoma↗

The capacity of peripheral blood stem cells mobilised with chemotherapy plus G-CSF to repopulate irradiated marrow stroma in vitro is similar to that of bone marrow.

After treatment of patients with intermediate or high grade non-Hodgkin lymphoma with chemotherapy plus G-CSF the numbers of haemopoietic progenitor cells in the circulation increased to a mean of 226-fold for mixed CFC (Mix-CFC), 278-fold for GM-CFC and 29-fold for erythroid burst forming unit (BFU-E). The mean increase was modest (7-12-fold) for patients treated with chemotherapy alone. Peripheral blood mononuclear cells harvested at the time of the peak in the numbers of progenitors, or 2-4 days before the peak, seeded onto irradiated marrow stroma in vitro, repopulated the stroma and generated active haemopoiesis at least as effectively as bone marrow cells on a cell per cell basis. This is in contrast to the poor repopulating capacity of pretreatment blood. The results indicate that not only the progenitor cells, but also the repopulating stem cells migrated into the blood after chemotherapy plus G-CSF in sufficient numbers to allow harvesting and successful grafting without the possible complication of late haemopoietic failure.

Adult↗