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Biomedical subjects

M Michelagnoli

Publications and source records attributed to M Michelagnoli.

3 recordsLinked to original sources

Single center experience of a new intensive induction therapy for ewing's family of tumors: feasibility, toxicity, and stem cell mobilization properties.

PURPOSE: To examine the feasibility, tolerability, and toxicity of an intensified induction regimen (vincristine, ifosfamide, doxorubicin, and etoposide [VIDE]) in patients with newly diagnosed Ewing's family of tumors (EFT); to assess ability to maintain dose-intensity, and predictability of peripheral-blood stem cell mobilization. PATIENTS AND METHODS: Thirty patients were treated with vincristine 1.4 mg/m2 (maximum 2 mg) on day 1, doxorubicin 20 mg/m2, ifosfamide 3 g/m2 plus mesna and etoposide 150 mg/m2 on days 1 to 3. Cycles were given every 21 days for up to six cycles. RESULTS: One-hundred and seventy cycles of VIDE were given. The median treatment interval was 21 days (21 to 42) and nadir count: hemoglobin 8.3 (6.3 to 11.9), neutrophils 0.045 (0.0 to 2.1), and platelets 45 (3 to 343). There were 96 episodes of infection requiring hospitalization (56%). Growth factor support reduced infectious complications by 34%. Etoposide dose was reduced, or omitted, in 24% of cycles. Four patients did not complete six cycles due to unacceptable toxicity and one patient progressed on treatment. Twenty patients underwent peripheral-blood stem cell harvesting, 15 after cycle 3, and five after cycle 4. Median CD34+ yield was 4.6 x 106/kg per patient (1.8 to 14.5). Overall response to treatment, measured in 24 patients, was 88%. Seven of 11 patients undergoing surgery achieved greater than 90% necrosis of tumor (64%). CONCLUSION: VIDE is an effective induction regimen with substantial but acceptable toxicity that allows predictable mobilization of stem cells. Maintenance of dose-intensity is feasible in the majority of patients. Growth factors play a role in maintaining dose-intensity and reduce infectious complications.

Adolescent↗

Thiopurine methyltransferase deficiency in childhood lymphoblastic leukaemia: 6-mercaptopurine dosage strategies.

Daily 6-mercaptopurine (6MP) forms the backbone of continuing chemotherapy for childhood lymphoblastic leukaemia (ALL). A major metabolic route is catalysed by thiopurine methyltransferase (TPMT). TPMT deficiency occurs in 1 in 300 individuals and results in high concentrations of thioguanine nucleotides (TGNs), cytotoxic 6MP metabolites. A leukaemic child taking 6MP repeatedly developed profound pancytopenias. TPMT deficiency was confirmed. TGN formation was then studied on attenuated 6MP dosages. Four weekly oral doses of 75 mg/m2 6MP produced TGNs of 2348 pmol/8 x 10(8) red cells, nearly double the maximum TGNs recorded in ALL children with TPMT activity taking long term daily 75 mg/m2 6MP. Grossly elevated TGN concentrations were also produced at 10% standard 6MP dosage (7.5 mg/m2 daily), accompanied by unacceptable 6MP toxicity (neutropenia, diarrhoea, vomiting). The child was eventually stabilised on 10% alternate day therapy and after 15 weeks TGNs were 1670 pmol, just above the upper end of the TGN range for ALL children with TPMT activity.

Antimetabolites, Antineoplastic↗