Biomedical subjects

G Rosti

Publications and source records attributed to G Rosti.

166 records · Page 10Linked to original sources

PubMedDate not supplied

Donor origin of hematopoiesis after a case of allogeneic transplantation with cryopreserved marrow.

In allogeneic marrow transplantation (BMT), fresh donor marrow is generally given like a simple transfusion immediately after collection. Cryopreservation, on the other hand, is extensively used in autologous marrow transplantation (ABMT). However, there could be a few instances in which donor marrow should be cryopreserved for later reinfusion mainly because of the donor's inability, for logistic or medical reasons, to undergo marrow harvesting immediately prior to transplantation. We wish to describe a case of ALL transplanted with donor harvested earlier and cryopreserved. The bone marrow was cryopreserved with 10% DMSO in a controlled rate freezer and stored for 1 month in liquid nitrogen. The VNTR (variation number tandem repeat) technique was used to demonstrate the donor origin of blood cells. Hematological reconstitution was rapidly achieved and we demonstrated the allogeneic origin of the recipient's blood cells. We confirm the possibility of using cryopreserved marrow stem cells for BMT. Cryopreservation of stem cells from other origin may also find a useful application in BMT.

Adult↗

PubMedDate not supplied

Itraconazole can increase systemic exposure to busulfan in patients given bone marrow transplantation. GITMO (Gruppo Italiano Trapianto di Midollo Osseo).

Busulfan (BU) is an alkylating drug frequently used to prepare patients for bone marrow transplantation (BMT). Several studies have documented that there is important interpatient variability in BU disposition and systemic exposure, and that other drugs with a common metabolic pathway are capable of influencing BU clearance. We compared the BU pharmacokinetics and pharmacodynamics of 13 patients given BMT and receiving BU and itraconazole, with those of 26 matched controls who did not receive any anti-fungal agent, and with those of 13 matched patients treated with fluconazole as prophylaxis against fungal infections. The effect of itraconazole was best reflected in BU clearance since the BU dose was modified in some patients. BU clearance was decreased by an average of 20% in patients receiving itraconazole as compared to control patients and patients receiving fluconazole (p < 0.01). Mean BU clearance was 7.653 +/- 1.871 l/hr.m2 in the itraconazole patients, 10.103 +/- 2.007 l/hr.m2 in the fluconazole group and 9.373 +/- 1.702 l/hr.m2 in the control group. In this study itraconazole, but not fluconazole, markedly affected the pharmacokinetics of BU as an increase of BU plasma concentrations was observed. The nature of this interaction has not yet been fully characterized. Itraconazole and its analogues are inhibitors of both cytochrome P450 and lipoxygenase and since itraconazole can modulate BU pharmacokinetics, oxidative catabolism is probably a determinant of BU metabolism. This hypothesis should be tested in human metabolic studies.

Adolescent↗

PubMedDate not supplied

[High-dose chemotherapy and peripheral hemtopoietic cells (PBPC) in solid tumors].

High-dose chemotherapy is a policy which is increasing in the field of solid tumors both in Europe and in North America. Hundreds of patients undergo ABMT or PBPCT in Europe every year especially for breast carcinoma. Waiting for the results of several ongoing trials, high-dose chemotherapy has shown to be of extreme interest in the adjuvant setting of patients with high risk breast cancer in phase II trials. The best results had been reported by Peters and Gianni; with a minimum follow-up of 5 years 65 and 56% of their patients with ten or more axillary lymph nodes are alive disease free. These results are better than any others with standard doses. The only one published trial (from South Africa) on advanced disease clearly favours high-doses of cyclophosphamide, mitoxantrone and etoposide versus standard doses of cyclophosphamide, mitoxantrone and vincristine in terms of overall survival and time to relapse. The use of PBPC replacing ABMT has allowed an easier tolerability of the procedure and a reduction of the costs. There is a clear reduction of the toxic death rate to 1% in 1995 for breast cancer patients compared with 20% of fifteen years ago. Germ cell tumors in responding relapse after salvage chemotherapy seem to be ideal candidates for ABMT/PBPC programs with an expected 40% disease free survival. The clinical impact of the PBPC contamination by tumor cells is still nowadays a matter of debate at least for breast carcinoma and neuroblastoma. This review will focus on the present situation of high-dose chemotherapy for solid tumors with some insights to new technologies and their applications.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Response to sequential treatment with lymphoblastoid interferon-alpha in patients with Ph+ chronic myeloid leukemia unresponsive to recombinant interferon-alpha (rIFN alpha 2a) and neutralizing-rIFN alpha 2a antibodies negative.

Nine Ph+ CML patients in chronic phase who were hematologically and/or karyotypically unresponsive to recombinant-IFN alpha 2a (rIFN alpha 2a) and neutralizing-rIFN alpha 2a Abs negative were shifted from rIFN alpha 2a to lymphoblastoid-IFN alpha (IFN alpha-Ly) therapy. After 3 months of IFNa-Ly treatment, the hematologic response was reinduced in 3 out of the 6 pts who were resistant to previous rIFN alpha 2a therapy, and was maintained in 2 out of 3 patients who were hematologically but not karyotypically responsive to rIFN alpha 2a. After 6 and 12 months, the hematologic response was progressively lost, being present only in 3 out of 7 and in 2 out of 3 evaluable patients respectively. None of the hematologically responsive patients achieved a karyotypic response (Ph neg. metaphases-0%). One patient, who was hematologically responsive, continued being treated with IFN alpha-ly for 36 months but he did not achieve any karyotypic response. The results of this study suggest that in the unresponsive and neutralizing-rIFN alpha 2a Abs negative CML patients a change in therapy, by using a non cross-reactive type of IFN alpha, would not be advantageous.

Adult↗