[Effect of total body irradiation on erythropoiesis in 20-day-old rats].
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Biomedical subjects
Publications and source records attributed to V Rizzoli.
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The transport of L-carnitine and analogs in exchange with previously loaded 3H-carnitine has been studied in heart tissue slices. The slices are first loaded with 3H-carnitine; then they are transferred in vessels containing the same medium with possible exchangers. Acetylcarnitine, L-carnitine, D-carnitine and deoxycarnitine exchange with internal 3H-carnitine. The exchange with acetylcarnitine, the largest among the compounds tested, appears to be a saturation process and is not affected either by oxidative phosphorylation and glycolysis inhibitors. The exchange of external acetylcarnitine with internal carnitine support that also in vivo heart tissue can utilize acetylcarnitine present in blood. Finally the observed deoxycarnitine/carnitine exchange, occurring in the reverse direction, may be the mechanism by which the heart accumulate external carnitine in exchange with endogenous deoxycarnitine.
In this study, nine patients with non-Hodgkin's lymphoma (n = 6) and Hodgkin's disease (n = 3) receiving different cytotoxic chemotherapy regimens were given granulocyte colony-stimulating factor (G-CSF) (5 micrograms/kg/day) from 48 hours after the end of chemotherapy to 48 hours before the next chemotherapy administration. The decrease in mean absolute neutrophil counts (ANC) and in mean platelet (Plt) counts was not significant when pre-therapy counts were compared with post-therapy ones (p < 0.375 and p > 0.4, respectively). The mean actual dose intensity was 92% (range 68-100%). G-CSF treatment after chemotherapy reduces neutropenia and permits administration of the full chemotherapy program. A wash-out period between G-CSF treatment and chemotherapy administration is needed to prevent the detrimental effect of chemotherapy on leukocyte and platelet recovery when repeated cycles of cytotoxic drugs and G-CSF are administered.
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The clonogenic capacity of human umbilical cord blood (UCB) has been evaluated in several studies which found high numbers of primitive hematopoietic progenitor cells. Recently, UCB progenitor cells were shown to possess significant advantages over bone marrow (BM) in terms of proliferative capacity and immunologic reactivity. Therefore UCB has come to be considered an attractive source of hematopoietic stem cells for both research and clinical applications. UCB has been used in the treatment of diseases potentially curable by bone marrow transplantation (BMT). Seventy-one transplants have been performed world-wide using UCB cells, and the results have been reported to the International Cord Blood Transplant Registry (ICBTR). Since UCB cells appear to be less alloreactive than BM cells, studies have been carried out to determine the most successful procedures for collection and fractionation of UCB and to quantify precisely the progenitor/stem cell content. The different techniques for quantifying progenitor/stem cells as well as the results of related and unrelated UCB treatments will be reviewed. Further clinical applications of UCB involving gene therapy and stem cell expansion will be discussed.
BACKGROUND AND OBJECTIVE: Allogeneic bone marrow transplantation remains the only potentially curative treatment for CML, but more than 70% of patients will be ineligible for allogeneic marrow transplant either because they do not have a suitable HLA-matched related or unrelated donor or because they are more than 50 years old. Several experimental and clinical findings support a role for autologous stem cell transplantation (ASCT) in CML. It has been suggested that in the early phase following autografting the Ph-negative clone has a proliferative advantage over the Ph-positive clone. We hypothesized that post-transplant GM-CSF administration could reactivate the functional activity of quiescent normal progenitors and prolong the duration of the post-transplant proliferative advantage of Ph-negative over Ph-positive progenitors. In order to evaluate the effect of post-transplant GM-CSF administration, a pilot clinical study was performed in which CML patients resistant to IFN-alpha therapy were autografted with unmanipulated marrow or blood cells and given prolonged GM-CSF therapy post-transplant. METHODS: Five adult CML patients conditioned with the BAVC regimen were reinfused with either marrow (n = 2) or blood (n = 3) cells and given granulocyte-macrophage colony-stimulating factor (GM-CSF). Recombinant GM-CSF was initially administered at standard dosage (5 micrograms/kg/day) until a white blood cell count > or = 2 x 10(9)/L was achieved on two consecutive examinations, and thereafter at a low dose (1 microgram/kg/day) for 5 to 9 months. On a weekly basis, GM-CSF was discontinued and hydroxyurea (1,000 mg/d) was given for two days. RESULTS: Evidence of trilineage engraftment was observed in all cases. At autografting, 3 out of the 5 patients revealed 8-9% Ph-negative metaphases. During the initial phase of hematopoietic regeneration, direct cytogenetic analysis revealed 81% and 100% Ph-negative metaphases in two cases; nonleukemic hematopoiesis progressively decreased and was no longer detectable at +9 months. One patient showed cyclic Ph-negative hematopoiesis that appeared 3 months following autografting and peaked at +4 and +8 months. The fourth patient showed a low percentage (20%) of Ph-negative metaphases 1 month after ASCT, followed by a significant expansion of nonleukemic hematopoiesis, which could be detected up to month +13. No evidence of Ph-negative hematopoiesis could be detected in one patient. Three patients are in chronic phase 28, 30 and 31 months after autografting, respectively, and two patients evolved into blast crisis. INTERPRETATION AND CONCLUSIONS: This pilot study demonstrates that combined GM-CSF and hydroxyurea therapy seems to be effective in inducing and/or prolonging a transient period of Ph-negative hematopoiesis. The late appearance of Ph-negative hematopoiesis detected in two patients suggests an antileukemic activity of the combined GM-CSF/hydroxyurea therapy rather than an antileukemic effect of the conditioning regimen.