References of "Haematologica"
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See detailModulation of homing properties of primitive progenitor cells generated by ex vivo expansion.
Foguenne, Jacques ULg; Huygen, Sandra; Greimers, Roland ULg et al

in Haematologica (2005), 90(4), 445-51

BACKGROUND AND OBJECTIVES: The maintenance of adequate interactions with the bone marrow (BM) microenvironment is critical to ensure efficient homing of ex vivo-expanded hematopoietic cells. This study ... [more ▼]

BACKGROUND AND OBJECTIVES: The maintenance of adequate interactions with the bone marrow (BM) microenvironment is critical to ensure efficient homing of ex vivo-expanded hematopoietic cells. This study was intended to assess adhesion and migration properties of long-term culture-initiating cells (LTC-IC) harvested after self-renewal division in ex vivo culture and to determine their susceptibility to growth-inhibitory signals mediated by adhesion to BM stromal ligands. DESIGN AND METHODS: We used cell tracking to isolate primitive LTC-IC that had accomplished 1 or 2 divisions ex vivo. Adhesion, migration and growth inhibition of divided LTC-IC were determined in the presence of purified BM ligands, and compared to the properties of uncultured LTC-IC. RESULTS: As compared to undivided LTC-IC, adhesion and migration mediated by very late antigen (VLA)-4 integrin across both vascular cell adhesion molecule-1 (VCAM-1) and fibronectin (Fn) were downregulated in post-mitotic LTC-IC. Conversely, binding and motility via VLA-5 across Fn were stimulated. No changes occurred in LTC-IC interactions with intercellular adhesion molecule-1 (ICAM-1) or with E- or P-selectin. Proliferation of uncultured LTC-IC was inhibited by VLA-4-mediated binding to VCAM-1 and the CS-1 domain of Fn, as well as binding to P-selectin. Growth of ex vivo-generated LTC-IC became unresponsive to these 3 ligands but was suppressed through VLA-5 engagement by the cell binding domain of Fn. INTERPRETATION AND CONCLUSIONS: The generation of LTC-IC in expansion culture is associated with functional alterations of adhesion receptors, modulating not only binding and migration in the BM but also responsiveness to adhesion-mediated growth inhibitory signals. Such changes may limit homing and engraftment of expanded primitive stem/progenitor cells. [less ▲]

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See detailMature erythrocyte indices: new markers of iron availability.
Bovy, Christophe ULg; Gothot, André ULg; Krzesinski, Jean-Marie ULg et al

in Haematologica (2005), 90(4), 549-51

This study was aimed at evaluating mature erythrocyte indices as new markers of iron status. Contrarily to those in the whole red blood cell (RBC) population, mature erythrocyte parameters are valid ... [more ▼]

This study was aimed at evaluating mature erythrocyte indices as new markers of iron status. Contrarily to those in the whole red blood cell (RBC) population, mature erythrocyte parameters are valid markers of iron status that remain independent of erythropoietic activity. When reticulocytosis is low, these parameters are similar to whole RBC parameters. [less ▲]

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See detailEfficacy of recombinant human erythropoietin therapy started one month after autologous peripheral blood stem cell transplantation.
Vanstraelen, Gaetan; Baron, Frédéric ULg; Frere, Pascale ULg et al

in Haematologica (2005), 90(9), 1269-70

On day 30 after autologous peripheral blood stem cell transplantation (PBSCT), 20 patients were randomized to receive either erythropoietin at a dose of 500 U/kg/week s.c. (Epo group) or no treatment ... [more ▼]

On day 30 after autologous peripheral blood stem cell transplantation (PBSCT), 20 patients were randomized to receive either erythropoietin at a dose of 500 U/kg/week s.c. (Epo group) or no treatment (control group). After 3 weeks, hemoglobin (p<0.0001) and serum transferrin receptor (p<0.0001) concentrations were higher in the Epo group. Hb response (+2 g/dL) was achieved in 100% vs 28% (p<0.0001) and Hb correction (> or =13 g/dL) in 70% vs 10% (p=0.0238) of the patients, respectively. This is the first randomized study showing an efficacy of erythropoietin therapy on Hb levels after autologous PBSCT. [less ▲]

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See detailDifferential expression of vascular endothelial growth factor and its receptors in hematopoietic and fatty bone marrow: evidence that neuropilin-1 is produced by fat cells.
Belaid, Zakia ULg; Hubint, Frederique; Humblet, Chantal ULg et al

in Haematologica (2005), 90(3), 400-1

Vascular endothelial growth factor (VEGF), its receptors (VEGFR-1, VEGFR-2) and neuropillin-1 (NRP-1) are expressed at variable levels in bone marrow. NRP-1expression is higher in fatty bone marrow than ... [more ▼]

Vascular endothelial growth factor (VEGF), its receptors (VEGFR-1, VEGFR-2) and neuropillin-1 (NRP-1) are expressed at variable levels in bone marrow. NRP-1expression is higher in fatty bone marrow than in hematopoietic marrow. Adipocytes are responsible for NRP-1 expression suggesting that they may play a role in hematopoiesis by producing NRP-1 or that NRP-1 may regulate adipocyte activity. [less ▲]

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See detailAllogeneic stem cell transplantation in acute lymphoblastic leukemia and non-Hodgkin's lymphoma for patients <= 50 years old in first complete remission: results of the EORTC ALL-3 trial
Labar, Boris; Suciu, Stefan; Zittoun, Robert et al

in Haematologica (2004), 89(7), 809-817

Background and Objectives. In the EORTC ALL-3 trial, the efficacy of allogeneic transplantation was compared with that of autologous marrow transplantation and maintenance chemotherapy in patients less ... [more ▼]

Background and Objectives. In the EORTC ALL-3 trial, the efficacy of allogeneic transplantation was compared with that of autologous marrow transplantation and maintenance chemotherapy in patients less than or equal to 50 years who reached CR. Design and Methods. Among 340 patients who entered the study, 279 were less than or equal to 50 years old. Out of these, 220 reached CR, 184 patients started consolidation and were HLA typed; 68 had a donor and 116 had no sibling donor. The median follow-up was 9.5 years; 93 patients relapsed, 26 died in CR, and overall 116 patients died. Allogeneic transplantation was performed in 47 (68%) patients with a donor while autologous transplantation or maintenance chemotherapy was given to 84 (72%) patients without a sibling donor. Results. The 6-year disease-free survival rate was similar in the groups with and without donor [38.2% (SE=5.9%) vs. 36.8% (SE=4.6%), hazard ratio 1.01, 95% CI 0.67-1.53]. Comparing the donor group with the no donor group, the former had a lower relapse incidence (38.2% vs. 56.3%, p=0.001), but a higher cumulative incidence of death in CR (23.5% vs. 6.9%, p=0.0004). The 6-year survival rates were similar [41.2% (SE=6.0%) vs. 38.8% (SE=4.6%)]. Interpretation and Conclusions. This trial did not show that allogeneic transplantation, when a sibling donor is available, produces a better outcome than the policy of offering autotransplantation or chemotherapy in the absence of a donor. [less ▲]

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See detailImpact of erythropoietic activity on red cell parameters in chronic renal failure patients.
Bovy, Christophe ULg; Krzesinski, Jean-Marie ULg; Gothot, André ULg et al

in Haematologica (2004), 89(6), 748-9

We measured red cell parameters during recombinant human erythropoietin (rHuEPO) therapy associated with appropriate iron supplementation in chronic hemodialysis patients. Increased erythropoietic ... [more ▼]

We measured red cell parameters during recombinant human erythropoietin (rHuEPO) therapy associated with appropriate iron supplementation in chronic hemodialysis patients. Increased erythropoietic activity led to a bias in red cell parameter determination. The percentage of hypochromic red blood cells, usually used as the most effective predictor of response to iron supplementation, increased following the appearance of a younger red cell population since the same Hb content in these younger, larger cells gives a lower Hb concentration. [less ▲]

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See detailPlatelet expression of non-functional P2X1delL ion channels in mice reduces arterial thrombosis
Oury, Cécile ULg; Daenens, Kim; Feijge, Marion et al

in Haematologica (2004)

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See detailCD34+ cell dose predicts costs after autologous peripheral blood stem cell transplantation for breast cancer.
Baron, Frédéric ULg; Copizza, Sandra; Baudoux, Etienne ULg et al

in Haematologica (2004), 89(9), 1146-8

We assessed the effect of CD34+ cell dose on costs in breast cancer patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. Mean hospitalization costs were 26,992.9+/-9582.9 for ... [more ▼]

We assessed the effect of CD34+ cell dose on costs in breast cancer patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. Mean hospitalization costs were 26,992.9+/-9582.9 for patients receiving a CD34+ cell dose <5 x 10(6) cells/kg versus 22,339.4+/- 5471.1 for those receiving >5 x 10(6) CD34+ cells/kg (p=0.0065). [less ▲]

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See detailLong-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation.
Schetelig, Johannes; Fetscher, Sebastian; Reichle, Albrecht et al

in Haematologica (2003), 88(11), 1272-8

BACKGROUND AND OBJECTIVES: Patients with angioimmunoblastic T-cell lymphoma (AIL) have a poor prognosis with conventional treatment. DESIGN AND METHODS: We initiated an EBMT-based survey studying the ... [more ▼]

BACKGROUND AND OBJECTIVES: Patients with angioimmunoblastic T-cell lymphoma (AIL) have a poor prognosis with conventional treatment. DESIGN AND METHODS: We initiated an EBMT-based survey studying the impact of high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation in patients with AIL. Data on 29 patients, who were transplanted between 1992 and 1998 in 16 transplant centers, were collected on standardized documentation forms. RESULTS: The median age at transplantation was 53 years. HDCT was given as part of 1st-line therapy (N=14; 48%) or 2nd/3rd-line therapy (N=15; 52%). Regimens for the mobilization of peripheral blood stem cells (PBSC) included VIPE (N=7; 26%), DexaBEAM (N=6; 22%), CHOP-like regimens (N=6; 22%), other regimens (N=5; 19%) or alternatively growth factor alone (N=3; 11%). The median yield of PBSC was 3.8x106 CD34+cells/kg. Two patients received autologous bone marrow. The HDCT consisted of BEAM-type regimens in 16 patients, ICE-type regimens in 7, and other regimens in 6 patients. There was one treatment-related death. The rate of complete remissions increased from 45% before HDCT to 76% after HDCT. As of January 2003, after a median observation time of living patients of 5 years (range 2.5 to 10 years), 14 patients have died (13 from progressive disease), and 15 patients are alive. The probability of 5-year overall and event-free survival was 44% (95% CI, 22% to 66%) and 37% (95% CI, 17% to 57%), respectively. Long-term disease-free survival was observed in patients transplanted during 1st-line treatment as well as in the context of 2nd/3rd-line therapy. INTERPRETATION AND CONCLUSIONS: There is evidence that AIL is susceptible to high-dose chemotherapy. HDCT and autologous stem cell transplantation should be considered in selected patients with AIL. [less ▲]

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See detailPrediction of response and other improvements on the limitations of recombinant human erythropoietin therapy in anemic cancer patients.
Beguin, Yves ULg

in Haematologica (2002), 87(11), 1209-21

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 ... [more ▼]

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. [less ▲]

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See detailIncreased platelet reactivity to collagen in transgenic mice overexpressing the P2X1 ion channel.
Oury, Cécile ULg; Kuijpers, marijke; Toth-Zsamboki, Emese et al

in Haematologica (2002), 87

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See detailP2X1-mediated activation of Ca2+-calmodulin leads to myosin light chain and ERK2 phosphorylation in human platelets.
Toth-Zsamboki, Emese; Oury, Cécile ULg; De Vos, Rita et al

in Haematologica (2002), 87

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See detailCa2+ influx via the platelet P2X1 ion channel contributes to collagen-induced platelet activation.
Hoylaerts, Marc; Oury, Cécile ULg; Toth-Zsamboki, Emese et al

in Haematologica (2002), 87

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See detailPre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation.
Baron, Frédéric ULg; Siquet, Jean; Schaaf-Lafontaine, Nicole ULg et al

in Haematologica (2002), 87(1), 78-88

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 ... [more ▼]

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. [less ▲]

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See detailReticulocyte transferrin receptor (TfR) expression and contribution to soluble TfR levels.
R'Zik, Samir ULg; Loo, Martine; Beguin, Yves ULg

in Haematologica (2001), 86(3), 244-51

BACKGROUND AND OBJECTIVES: Transferrin receptor (TfR) expression in erythroid cells is regulated by a number of factors, including iron status and erythropoietin (Epo) stimulation. However, the impact of ... [more ▼]

BACKGROUND AND OBJECTIVES: Transferrin receptor (TfR) expression in erythroid cells is regulated by a number of factors, including iron status and erythropoietin (Epo) stimulation. However, the impact of these factors on reticulocyte TfR expression in vivo has never been studied. A soluble form of TfR (sTfR) is present in serum in proportion to the mass of cellular TfR. Although sTfR shedding by reticulocytes and erythroblasts has been demonstrated in vitro, the contribution of reticulocyte TfR to serum sTfR has never been evaluated in vivo. DESIGN AND METHODS: We measured directly the total number of reticulocyte TfR in normal rats of different age and iron status, as well as in animals experiencing various conditions and treatments aimed at altering erythropoietic activity and iron status, including rHuEpo therapy, hemolytic anemia, phlebotomies, hypertransfusions, thiamphenicol-induced red cell aplasia or inflammation. In addition, we examined the impact of repeated hypertransfusions with normal, reticulocyte-poor and reticulocyte-rich blood on serum sTfR levels. RESULTS: The number of TfR molecules per reticulocyte was around 50,000 in young rats but was around 100,000 in older animals. These values remained constant in most conditions and in particular were not influenced by iron supplementation or iron overload. However, functional iron deficiency as well as rHuEpo therapy resulted in increased reticulocyte TfR expression. In addition, TfR numbers in reticulocytes were elevated in the early phase of recovery after acute hemolysis or red cell aplasia but normalized soon after. Hypertransfusion experiments clearly demonstrated that reticulocytes can contribute substantially to sTfR levels in vivo. INTERPRETATION AND CONCLUSIONS: TfR numbers are regulated in vivo by the same factors as in vitro, in particular iron deficiency and erythropoietin stimulation. Circulating reticulocytes contribute significantly to serum sTfR levels. [less ▲]

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