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Yves Beguin

Publications and source records attributed to Yves Beguin.

42 records · Page 3Linked to original sources
PubMed2002

Retrospective comparison of CD34-selected allogeneic peripheral blood stem cell transplantation followed by CD8-depleted donor lymphocyte infusions with unmanipulated bone marrow transplantation.

We have previously reported the feasibility of allogeneic CD34-selected PBSC transplantation followed by pre-emptive CD8-depleted DLI (study group). In this report, we retrospectively compare the clinical outcome of the 24 patients included in this study with an historical group of 35 patients receiving unmanipulated marrow (BMT group). Patients in the study group had significantly faster neutrophil and platelet recovery and were discharged earlier than BMT patients. The actuarial 150-day (after DLI) probability of developing grade II-IV acute GVHD was 28% for the study group versus 62% for the BMT group (p=0.002). The actuarial 2-year probability of developing chronic GVHD was similar (37 versus 36% (NS)) but chronic GVHD was significantly delayed in the study group (p=0.003). The actuarial 2-year probability of relapse was 30% in the study group versus 33% in the BMT group (NS). The actuarial 2-year probability of survival was 45% in the study group versus 43% in the BMT group (NS). We conclude that allogeneic transplantation of CD34-selected PBSC followed by pre-emptive CD8-depleted DLI is feasible with rapid engraftment and minimizes the risk of severe GVHD. Large prospective trials are required to confirm these results.

Adolescent↗
PubMed2002

Nonmyeloablative stem cell transplantation with CD8-depleted or CD34-selected peripheral blood stem cells.

To decrease the incidence of graft-versus-host disease (GVHD) observed after nonmyeloablative stem cell transplantation (NMSCT), we studied the feasibility of CD8-depleted or CD34-selected NMSCT followed by CD8-depleted preemptive donor lymphocyte infusion (DLI) given in incremental doses on days 40 and 80. Fourteen patients with high-risk malignancies and an HLA-identical sibling (n = 8) or alternative donor (n = 6) but ineligible for a conventional transplant were included. Nonmyeloablative conditioning regimen consisted in 2 Gy total body irradiation (TBI) alone, 2 Gy TBI and fludarabine (previously untreated patients) or cyclophosphamide and fludarabine (patients who had previously received > or =12 Gy TBI). Patients 1-4 (controls) received unmanipulated peripheral blood stem cells (PBSC) and DLI and patients 5-14 CD8-depleted or CD34-selected PBSC followed by CD8-depleted DLI. Post-transplant immunosuppression was carried out with cyclosporine A (CsA) and mycophenolate mofetil (MMF). Initial engraftment was seen in all patients, but 1 patient (7%) later rejected her graft. The actuarial 180-day incidence of grades II-IV acute GVHD was 75% for patients 1-4 versus 0% for patients 5-14 (p = 0.0019). Five of 14 patients were in complete remission (CR) 180 days after the transplant and 6/14 had partial responses. The 1-year survival rate was 69%, and nonrelapse and relapse mortality rates were 16 and 18%, respectively. We conclude that CD8-depleted or CD34-selected NMSCT followed by CD8-depleted DLI is feasible and considerably decreases the incidence of acute GVHD while preserving engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.

Adolescent↗
PubMed2002

Stunting may determine the severity of malaria-associated anemia in African children.

OBJECTIVE: Evidence from previous studies that malnourished children are protected against malaria is controversial. In individuals repeatedly exposed to malaria, immunity may develop first against severe disease, then against pyrogens, and last, against parasites. If this is true, this would suggest that reduced immune function that may exist in stunted children exacerbates the severity of malarial signs and symptoms, rather than the occurrence of parasitemia. On the other hand, several studies have suggested that malnourished children are protected to some degree against malaria. Our aim was to evaluate whether observational data support the hypothesis that nutritional inadequacies that cause stunting modify the associations between malaria and hematologic indicators such as hemoglobin concentration and serum concentrations of C-reactive protein and soluble transferrin receptor (sTfR). We showed earlier that increased serum concentrations of these receptors in asymptomatic malaria may be explained, at least in part, by increased erythropoiesis to compensate for malaria-induced hemolysis. METHODOLOGY: Community-based cluster survey among Kenyan children aged 2 to 36 months asymptomatic for malaria or anemia (n = 318). RESULTS: When adjusted for age and wasting, the malaria-associated decrease in mean hemoglobin concentration was 8.5 g/L and 15.8 g/L in nonstunted and stunted children, respectively. The malaria-associated increase in geometric mean serum concentrations of sTfR was 1.1-fold and 1.8-fold in nonstunted and stunted children, respectively. The malaria-associated increase in geometric mean serum concentrations of C-reactive protein was 1.4-fold and 2.3-fold in nonstunted and stunted children, respectively. Thus, children with malaria and those who were stunted suffered from more severe anemia and had higher serum concentrations of C-reactive protein and sTfR than would be expected from the combined effect of the 2 working independently. CONCLUSIONS: Our results are consistent with the notion that the nutritional inadequacies causing stunting also impair host immunity, thus increasing the degree to which malaria is associated with decreased concentrations of hemoglobin, with increased inflammation, and with increased iron demand in developing erythroblasts. Increased intake of micronutrients may not only reduce stunting and nutritional anemia, but also reduce malaria-associated anemia.

Anemia, Iron-Deficiency↗
PubMed2002

Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation.

BACKGROUND AND OBJECTIVES: To maximize graft-versus-leukemia (GVL) effects while minimizing the risk of graft-versus-host disease (GVHD), we undertook a study of allogeneic CD34-selected peripheral blood stem cell (PBSC) transplantation followed by CD8-depleted donor lymphocyte infusion (DLI). DESIGN AND METHODS: Twenty-four patients with advanced hematologic malignancies were included. PBSC were collected in matched (N=16) or one-mismatch (N=8) related donors and CD34-selected. On day 60, donors donated lymphocytes that were CD8-depleted and separated into 3 aliquots containing 2 x 10(6), 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 1-13) or into 2 aliquots containing 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 14-24). The 1st aliquot was infused on day 60 and the other 1 (2) cryopreserved and infused on days 100 (and 140). RESULTS: An average of 100%, 100% and 84% of the scheduled dose could be administered in DLI 1, 2 and 3, respectively. Although the study group was at very high risk of GVHD, the actuarial incidence of grade II-IV acute GVHD was 28% (13% for HLA-identical siblings) with only 1 patient developing grade III-IV GVHD (after DLI). The actuarial 2-year probability of extensive chronic GVHD was similarly low (13% for all patients and 0% for HLA-identical siblings). Individual cases as well as a 30% relapse rate (0% for standard-risk patients versus 55% for high-risk patients) indicated preservation of the GVL effect. INTERPRETATION AND CONCLUSIONS: We conclude that allogeneic transplantation of CD34-selected PBSC followed by pre-emptive CD8-depleted DLI is feasible with rapid engraftment and minimizes the risk of severe GVHD. Large prospective trials are required to prove that it preserves the GVL effect fully.

Adolescent↗
PubMed2002

Prediction of response and other improvements on the limitations of recombinant human erythropoietin therapy in anemic cancer patients.

BACKGROUND AND OBJECTIVES: The majority of cancer patients suffer from chronic anemia. While recombinant human erythropoietin (rHuEPO) offers many of the advantages of blood transfusions, response rates to this treatment are variable and in some trials a large proportion of patients (30 50%) did not respond. This failure may be due to factors related to the underlying disease, the chemotherapy given or functional iron deficiency. An accurate means of predicting response to rHuEPO would be beneficial to both healthcare providers and patients. EVIDENCE AND INFORMATION SOURCES: Data were identified by searches of the published literature, including PubMed, references from relevant reviews, and abstracts presented at recent international oncology and hematology meetings. Only papers in English published between 1990 and 2002 were included. References were selected according to direct relevance to the topic discussed and availability. STATE OF THE ART: The best algorithms for predicting response appear to be those combining an assessment of the adequacy of endogenous erythropoietin production together with some early indicators of erythropoietic marrow response. Further characterization of the dose-response relationship of erythropoietic agents may allow better understanding of ways in which response may be enhanced. Adequate iron availability could also contribute to better response rates. PERSPECTIVES: Further characterization of the predictors of response for current and upcoming erythropoietic agents may enhance the management of anemia associated with cancer, and provide more convenient, effective, and flexible therapy.

Algorithms↗