Biomedical subjects

Lidia De Felice

Publications and source records attributed to Lidia De Felice.

4 recordsLinked to original sources

PubMed2005

Histone deacetylase inhibitor valproic acid enhances the cytokine-induced expansion of human hematopoietic stem cells.

Ex vivo amplification of human hematopoietic stem cells (HSC) without loss of their self-renewing potential represents an important target for transplantation, gene and cellular therapies. Valproic acid is a safe and widely used neurologic agent that acts as a potent inhibitor of histone deacetylase activities. Here, we show that valproic acid addition to liquid cultures of human CD34+ cells isolated from cord blood, mobilized peripheral blood, and bone marrow strongly enhances the ex vivo expansion potential of different cytokine cocktails as shown by morphologic, cytochemical, immunophenotypical, clonogenic, and gene expression analyses. Notably, valproic acid highly preserves the CD34 positivity after 1 week (range, 40-89%) or 3 weeks (range, 21-52%) amplification cultures with two (Flt3L + thrombopoietin) or four cytokines (Flt3L + thrombopoietin + stem cell factor + interleukin 3). Moreover, valproic acid treatment increases histone H4 acetylation levels at specific regulatory sites on HOXB4, a transcription factor gene with a key role in the regulation of HSC self-renewal and AC133, a recognized marker gene for stem cell populations. Overall, our results relate the changes induced by valproic acid on chromatin accessibility with the enhancement of the cytokine effect on the maintenance and expansion of a primitive hematopoietic stem cell population. These findings underscore the potentiality of novel epigenetic approaches to modify HSC fate in vitro.

AC133 Antigen↗

PubMed2003

Intermediate-dose cyclophosphamide and granulocyte colony-stimulating factor is a valid alternative to high-dose cyclophosphamide for mobilizing peripheral blood CD34+ cells in patients with multiple myeloma.

Peripheral blood stem cells (PBSC) are widely used in the setting of dose-intensive chemotherapies in patients with multiple myeloma (MM). Although the granulocyte colony-stimulating factor (G-CSF), following chemotherapy or not, is considered the standard growth factor for mobilizing PBSC, the optimal chemotherapeutic regimen still remains to be defined. Cyclophosphamide (CTX) is an effective drug in the treatment of MM which is capable of mobilizing PBSC if followed by growth factors, even though administration of high-dose CTX (7 g/m(2)) results in severe toxicity requiring hospitalization and increasing costs. We have retrospectively analyzed the results obtained in 38 newly diagnosed MM patients treated with 1.2 g/m(2) CTX on days 1 and 3 combined with 40 mg dexamethasone daily for 4 days. The results were compared with those obtained in 25 newly diagnosed MM patients treated with 7 g/m(2) CTX. A higher number of CD34+ cells/kg was collected during the first leukapheresis and a statistically significant lower consumption of G-CSF was observed following two doses of 1.2 g/m(2) CTX compared to the 7 g/m(2) CTX dose. The possibility of treating patients with day-hospital regimens, with a satisfactory yield of hematopoietic cells harvested, may have relevant economic implications for treatment strategies in MM patients.

Adult↗

PubMed2003

One-year cyclosporine prophylaxis reduces the risk of developing extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation.

BACKGROUND AND OBJECTIVES: Chronic graft-versus-host disease (GVHD) remains the most common late complication of allogeneic stem cell transplantation, producing significant long-term morbidity and contributing to a substantial risk of late mortality. Chronic GVHD may be more common, more protracted and less responsive to current treatments after peripheral-blood stem cell (PBSC) transplantation than after bone marrow transplantation. The purpose of this retrospective cohort study was to determine whether the hazard of extensive chronic GVHD after allogeneic PBSC transplantation could be decreased by prolonging cyclosporine A (CsA) prophylaxis over 12 months. DESIGN AND METHODS: Fifty-seven consecutive patients with hematologic malignancies who had received a PBSC transplant from an HLA-identical sibling were evaluable for chronic GVHD. All patients began CsA tapering at day 50 but 2 different durations of immunosuppression were used: the first 36 patients were allocated to receive a 6-month course with tapering by 5% at weekly intervals (group A), while the following 21 received a 12-month course with tapering by 5% every 2 weeks (group B). RESULTS: The cumulative incidence of extensive chronic GVHD at 2 years was 69% (95% CI, 53-85%) for group A and 25% (95% CI, 3-47%) for group B with a significantly lower hazard in group B than in group A (HR=0.2; 95% CI, 0.07-0.57; p=0.0009). In multivariate analysis, the 12-month CsA tapering schedule was associated with a significantly decreased risk of extensive chronic GVHD (HR=0.2; 95% CI, 0.06-0.66; p=0.008). The hazard of transplant-related mortality, relapse and failure to survive in remission was not significantly different among the 2 groups. INTERPRETATION AND CONCLUSIONS: One-year CsA prophylaxis seems to be more effective than the standard six-month CsA regimen at preventing extensive chronic GVHD after PBSC transplant from an HLA-identical sibling. Conclusive assessment of the benefits of such prolonged immunosuppression, in terms of better quality of life and minor morbidity, requires both long-term follow-up to evaluate the rates of relapse and secondary tumors and a randomized setting.

Adolescent↗

PubMed2002

Standard versus alternative myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia.

BACKGROUND AND OBJECTIVES: To analyze the results of standard versus alternative myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia. DESIGN AND METHODS: From October 1986 to February 2000, 104 consecutive patients (male: n = 63; median age: 21, range 1.3-44.2 years) with high-risk acute leukemia underwent a non-T-cell depleted graft from an HLA-identical sibling following a standard or alternative myeloablative conditioning regimen. Sixty patients were affected by acute lymphoblastic leukemia (ALL) and 44 by acute myeloid leukemia (AML); the phase at transplant was >= 2nd complete remission (CR) in 76, untreated 1st relapse with < 20% blasts in 11, refractory leukemia or overt resistant relapse in 17. Pre-transplant regimens consisting of either 12 Gy fractionated total body irradiation (TBI) or 16 mg/kg busulphan (BU) combined with cyclophosphamide (CY) were defined standard (n = 38), whereas all other myeloablative regimens (TBI plus 60 mg/kg etoposide and three-drug combinations) were considered alternative (n = 66). RESULTS: No significant differences in terms of baseline characteristics, incidence and severity of either acute or chronic graft-versus-host disease (GVHD) were observed between the two groups, but a significantly higher proportion of patients prepared with an alternative regimen were not evaluable for chronic GVHD (36% vs 16%) (p = 0.026). Sixty-six patients died, 38 of relapse, 26 of transplant-related mortality (TRM) and 2 of other causes. Thirty-eight patients are still alive with a follow-up ranging from 0.7 to 13.8 years (median, 7.1 years); only 1 of 39 patients who relapsed after transplant is alive in CR at 5.7 years from relapse. At the median follow-up, the actuarial probabilities of overall survival, relapse and TRM for patients conditioned with standard and alternative regimens are respectively 52% vs 25% (95% CI, 36-68% vs 13-37%; p = 0.0163), 34% vs 58% (95% CI, 18-51% vs 43-73%; p = 0.0377) and 25% vs 32% (95% CI, 9-40% vs 19-44%; p = ns). After adjustment for diagnosis, age, period, leukemia phase, duration of 1st CR, GVHD prophylaxis and donor-recipient sex combination, the multivariate analysis showed that alternative regimens are associated with a significantly worse survival (hazard ratio 2.31; p = 0.0071) and relapse rate (hazard ratio 2.75; p = 0.0187). INTERPRETATION AND CONCLUSIONS: From this retrospective analysis we can conclude that the alternative myeloablative conditioning regimens we used did not improve the outcome of patients transplanted for high-risk acute leukemia.

Acute Disease↗