Biomedical subjects

G Comolli

Publications and source records attributed to G Comolli.

21 records · Page 2Linked to original sources

PubMedDate not supplied

Multicyclic dose-intensive chemotherapy with circulating progenitor cell support for high-risk primary breast cancer.

The feasibility and safety of the administration of multiple cycles of dose-intensive chemotherapy (CT) supported with repeated reinfusions of circulating progenitor cells (CPCs) were evaluated in a prospective study of adjuvant initial therapy of poor-prognosis breast cancer. Eighteen patients with resectable breast cancer involving >/= 10 axillary nodes or >/= 5 axillary nodes and negativity of the estrogen receptor status received a cycle of standard FEC regimen (5-FU 600 mg/m2, epirubicin 60 mg/m2, CTX 600 mg/m2, i.v. on day 1) followed by G-CSF as CPC mobilization technique. Collected CPCs were fractionated and reinfused, with G-CSF, after each of the 4 subsequent cycles of high-dose FEC (HD-FEC) (5-FU 750 mg/m2, epirubicin 120 mg/m2, CTX 3 g/m2, i.v.) planned at 21 day intervals. The median numbers of CD34+ cells and CFU-GM collected (with one or two leukaphereses per patient) were 9.7x10(6)/kg (range: 2.5-22.9) and 9.9x10(4)/kg (range: 1.9-27.3), respectively, and day 9 was the median first day of procedure (range: 8-12) after FEC. All patients received the 4 courses of HD-FEC (for a total of 72 cycles). Hemopoietic recovery was rapid after each cycle and there was no treatment-related delays in CT administration. Mucositis was the major non-hematological toxicity. There were 2, 3, 7 and 9 episodes of WHO grade 3/4 mucositis in cycles 1, 2, 3 and 4, respectively. These severe episodes lasted a median of 4 days (range: 2-6) but no patient required parenteral nutrition. The mean +/- SD total hospital stay lasted 10 +/- 2 days. The delivery of 4 cycles of dose-intensive FEC CT supported by CPCs (mobilized with a single course of standard-dose FEC + G-CSF) is feasible and safe. It could represent an effective alternative strategy to other more aggressive programs for the adjuvant therapy of high-risk early breast cancer.

Adult↗

PubMedDate not supplied

Cell cycle status and apoptosis of hematopoietic progenitor cells released into the peripheral blood after taxanes and granulocyte colony-stimulating factor in breast cancer patients.

Paclitaxel and its analogue docetaxel show a significant antitumor activity, particularly evident in breast cancer. Paclitaxel has also been proved to be effective as a peripheral blood progenitor cell (CPC) mobilizing agent. To optimize the use of active, disease-specific drugs as CPC priming, we have evaluated the effects of either paclitaxel or docetaxel both at standard dosages and followed by granulocyte colony-stimulating factor (G-CSF), on circulating CPC release and function in 18 patients with advanced breast cancer who had failed previous anthracycline-based regimens. The reported differences in biological behaviour between bone marrow and blood-derived hematopoietic progenitor cells and the ability of both paclitaxel and docetaxel to induce apoptosis, prompted us to simultaneously evaluate the cell cycle perturbations induced on CD34+ cells. Median CD34+ peaks were 24 microl (range: 10-58) in the paclitaxel-treated patients and 39 microl (range: 17-91), respectively, in the patients who received docetaxel. After paclitaxel, the percentage of CD34+ cells in S-phase was low (bromodeoxyuridine, BrdU, labelling index = 3.4+/-2%) with a concomitant presence of early apoptotic cells (8.1+/-3%). On the contrary, after docetaxel, the percentage of CD34+ cells in S-phase was higher (BrdU labelling index = 14.5+/-4%, p<0.05 vs. paclitaxel), while early apoptotic cells were detected at a similar rate (8. 6+/-3%, p = n.s. vs. paclitaxel). In conclusion, when used at standard dosages, with respect to paclitaxel + G-CSF, docetaxel + G-CSF is a more satisfactory tool to mobilize CPC and to induce them into the cell cycle. These data should be taken into account when combinations of docetaxel with other agents are explored as CPC mobilizing regimens for autografting.

Adult↗

PubMedDate not supplied

Bone marrow morphology and proliferative activity in acquired immunodeficiency syndrome.

Peripheral cytopenia has been reported in a number of patients with the acquired immunodeficiency syndrome (AIDS), but the mechanism of bone marrow (BM) failure is unclear. We have examined the BM morphology and cytokinetics of 16 untreated HIV-positive patients whose clinical condition ranged from asymptomatic (stage 1 WR and II CDC classifications) to overt AIDS (stage 6 WR and IV CDC classifications). BM aspirates and iliac crest threphine biopsies were obtained for myelogram and histologic examination, as well as for propidium iodide flow cytometric (FMC) DNA analysis. FCM data were compared with those from the BM of patients with solid tumors without BM involvement. Four patients had normal peripheral blood counts, 2 were anemic, 2 had granulocytopenia, 2 thrombocytopenia, 4 bicytopenia and 2 pancytopenia. BM cellularity was normal or increased, but only 2/16 patients had normal BM morphology. Ten patients had atypical lymphoid aggregates, relative plasmacytosis and eosinophilia, and 4 had typical myelodysplastic changes. There was no correlation between morphology and WR or CDC grade. The mean proliferative fraction (i.e. the percentage of cells in the S phase of the cell cycle) of the HIV-positive patients was 11% (range 5.5-18.3%). The mean value for the control patients was 15.1% (range 7.7-26.9%) (p less than 0.05). All patients had modal diploid DNA content without aneuploid clones. These data suggest that the mechanism of BM failure in HIV-positive patients lies in a reduced proliferative activity whose exact cause is still unclear.

Acquired Immunodeficiency Syndrome↗