Differential Expression of Cellular Prion Protein on Human Blood and Tonsil Lymphocytes
Antoine, Nadine ; ; Coumans, Bernard et al
in Haematologica (2000), 85(5), 475-80
BACKGROUND AND OBJECTIVE: The expression of cellular prion protein (PrPc) on the surface of peripheral lymphocytes has been previously reported, but little is known about its expression on lymphoid cells ... [more ▼]
BACKGROUND AND OBJECTIVE: The expression of cellular prion protein (PrPc) on the surface of peripheral lymphocytes has been previously reported, but little is known about its expression on lymphoid cells from secondary lymph organs. In this report, we compare the surface expression of PrPc on human blood lymphocytes and tonsil lymphocytes. DESIGN AND METHODS: This analysis was performed by cytometry on live lymphocytes isolated from healthy donors or from the tonsils of adults or children. RESULTS: Human peripheral lymphocytes and tonsillar lymphoid cells, but not erythrocytes or granulocytes, express PrPc at their surfaces. Interestingly, we found significantly less PrPc on freshly isolated tonsil lymphocytes, both B and T, than on blood cells. Although tonsil cells bear less PrPc than circulating blood lymphocytes, they are able to express high quantities of PrPc on their surface when placed in culture. However, contrary to previous results, mitogen stimulation does not affect this expression on B- or T-cells. INTERPRETATION AND CONCLUSIONS: We suggest that the PrPc expression by lymphocytes may be modified by interactions occurring during intratissular migration or during cell-to-cell contacts. Whether PrPc plays a role in intracellular communication at this location, as it does in the nervous system, remains an open question. [less ▲]Detailed reference viewed: 29 (4 ULg)
ADP-induced activation of the extracellular-regulated kinase/mitogen-activated protein kinase pathway via the ionotropic P2X1 receptor in platelets.
Oury, Cécile ; ; et al
in Haematologica (2000), 85Detailed reference viewed: 4 (1 ULg)
Persistent tumor 18F-FDG uptake after a few cycles of polychemotherapy is predictive of treatment failure in non-Hodgkin's lymphoma.
Jerusalem, Guy ; Beguin, Yves ; Fassotte, Marie-France et al
in Haematologica (2000), 85(6), 613-8
BACKGROUND AND OBJECTIVE: Early recognition of the ineffectiveness of chemotherapy could result in lower cumulative drug toxicity and tumor burden at the start of salvage therapy, which might improve ... [more ▼]
BACKGROUND AND OBJECTIVE: Early recognition of the ineffectiveness of chemotherapy could result in lower cumulative drug toxicity and tumor burden at the start of salvage therapy, which might improve clinical outcome. Therefore, we studied the value of (18)F-FDG PET for early evaluation of response in patients with non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: We studied 28 patients by (18)F-FDG PET after a median of 3 cycles of polychemotherapy. The presence or absence of abnormal (18)F-FDG uptake was correlated to clinical outcome (median follow-up: 17.5 months, range 4-47 months). RESULTS: Five of 28 patients still had increased (18)F-FDG uptake in one or more sites previously shown to be involved by lymphoma at baseline evaluation. Only one of these five patients entered complete remission (CR), whereas among the 23 patients with negative (18)F-FDG PET studies, two died of toxicity during chemotherapy and all the others entered clinical CR (p<0.00001). All five patients with and 7/21 patients without residual abnormal (18)F-FDG uptake relapsed or reprogressed (positive predictive value for relapse: 100%, negative predictive value: 67%). By Kaplan-Meier analysis, progression-free survival (PFS) at 1 and 2 years was respectively 20+/-18% and 0% for (18)F-FDG PET positive patients and 81+/-9% and 62+/-12% for (18)F-FDG PET negative patients (p=0.0001). Overall survival (OS) at 1 and 2 years was respectively 20+/-18% and 0% for (18)F-FDG PET positive and 87+/-7% and 68+/-11% for (18)F-FDG PET negative patients (p<0.0001). INTERPRETATION AND CONCLUSIONS: Persistent tumoral (18)F-FDG uptake after a few cycles of polychemotherapy is predictive of CR, PFS and OS in NHL. Further studies are warranted to determine whether (18)F-FDG PET has a predictive value independent from conventional prognostic factors. However, the sensitivity of qualitative (18)F-FDG PET imaging in identifying patients with a poor outcome was insufficient. Earlier evaluation after only one cycle of chemotherapy and quantitative analysis might increase the sensitivity of 18F-FDG PET is predicting treatment failure. [less ▲]Detailed reference viewed: 16 (2 ULg)
The belgian experience in unrelated donor bone marrow transplantation: identification of center experience as an important prognostic factor.
Dresse, Marie-Françoise ; ; et al
in Haematologica (1999), 84(7), 637-42
BACKGROUND AND OBJECTIVE: We reviewed all unrelated donor bone marrow transplants (UDBMT) performed in Belgium up to December 1995 to identify prognostic factors for relapse, transplant-related mortality ... [more ▼]
BACKGROUND AND OBJECTIVE: We reviewed all unrelated donor bone marrow transplants (UDBMT) performed in Belgium up to December 1995 to identify prognostic factors for relapse, transplant-related mortality and survival. DESIGN AND METHODS: A total of 163 UDBMT were performed in 92 males and 71 females aged 1-55 (median 26) years. Patients were transplanted for ALL (n=35), AML (n=34), CML (n=51), other myeloid malignancies (n=14), SAA (n=21) or miscellaneous other diseases (n=8). Most patients had advanced disease; a few patients were in CR1 (n=10) or early chronic phase (CP) of CML (n=5). RESULTS: Overall survival at 5 yrs was 17% (95% confidence interval: 8-32%), but survival was significantly better for patients with non-malignant disorders (55% at 4 yrs). The relapse rate +/-SE was projected to be 40 (28-54)% at 5 yrs, 36 (20-56)% for standard-risk and 68 (43-85)% for high-risk malignancies (p=0.0029). There was no relapse in CML patients transplanted in 1st CP compared to 68% at 4 yrs with more advanced CML (p=0.0033). Grade II-IV acute graft-versus-host disease (aGVHD) occurred in 55% by day 100 and was strongly modulated by age, ranging from 41% in <20-yr-old to 80% in >40-yr-old patients (p=0. 0021). Transplant-related mortality (TRM) was projected to be 72 (52-87)% at 5 yrs including 2 very late deaths from lung fibrosis and secondary cancer. Main causes of death were original disease in 27, secondary malignancy in 2, GVHD in 28, interstitial pneumonia in 21, other infections in 19, and miscellaneous toxic causes in 21 patients. In multivariate analysis, the relapse rate was strongly dependent on the disease status (p=0.0029), TRM being significantly worse with older age (p=0.0049), and overall survival being significantly worse in more advanced disease (p=0.0006), after a second transplant (p=0.0166), in centers of smaller size (p=0.0316) and in older patients (NS). INTERPRETATION AND CONCLUSIONS: Although results have improved somewhat in recent years, UDBMT remains a procedure with a high TRM. UDBMT should be performed in patients with less advanced diseases and in centers with more experience, particularly in the treatment of adult patients. [less ▲]Detailed reference viewed: 81 (6 ULg)
Erythropoietin and platelet production.
in Haematologica (1999), 84(6), 541-7
BACKGROUND AND OBJECTIVE: Erythropoietin (Epo) is the primary growth factor for the red cell lineage but treatment with recombinant human Epo (rHuEpo) has been shown to increase platelet counts. In ... [more ▼]
BACKGROUND AND OBJECTIVE: Erythropoietin (Epo) is the primary growth factor for the red cell lineage but treatment with recombinant human Epo (rHuEpo) has been shown to increase platelet counts. In several animal species treatment with rHuEpo stimulated platelet production, but platelet counts tended to normalize after 1-2 weeks and large, chronic doses even caused thrombocytopenia. This paper aims to review the evidence about the effects of Epo on megakaryopoiesis. INFORMATION SOURCES: I examined the literature published in journals covered by Medline(R)a concerning the effects of Epo, hypoxia and iron deficiency on megakaryopoiesis and platelets. The reference list of each article was reviewed to try to identify further contributions. STATE OF THE ART: In vivo data have shown that moderate Epo stimulation, i.e. that produced by standard doses of rHuEpo, short-term hypoxia or moderate iron deficiency, causes a moderate elevation of platelet counts, whereas intense Epo stimulation, as produced by high doses of rHuEpo, prolonged hypoxia or severe iron deficiency, causes some degree of thrombocytopenia. In the latter case, there appears to be a diphasic response to Epo, the initial positive response (a stimulation of platelet production) being followed by thrombocytopenia. Contrarily to the thrombocytopenia due to increased platelet destruction induced by other growth factors, Epo-induced thrombocytopenia is the result of an inhibition of platelet production. CONCLUSION AND PERSPECTIVE: Stem-cell competition between erythroid and platelet precursors appears to be the cause of these phenomena in situations of prolonged, intense stimulation by Epo. In vitro data support the existence of a common erythrocytic and megakaryocytic precursor. It remains to be determined whether these effects of rHuEpo are a result of the dose itself or of the magnitude of the erythropoietic effect of that dose. It is not known whether a lower dose given in a patient with decreased marrow function would bring about the same biological effects as those induced by high doses of rHuEpo in the presence of a normal marrow function. Caution should be exercised before using high doses of hematopoietic growth factors. [less ▲]Detailed reference viewed: 24 (0 ULg)
Peripheral blood progenitor cell collections in cancer patients: analysis of factors affecting the yields.
Sautois, Brieuc ; ; Baudoux, Etienne et al
in Haematologica (1999), 84(4), 342-9
BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify ... [more ▼]
BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify parameters that could predict the yield of PBPC after mobilization with chemotherapy (CT) with or without granulocyte colony-stimulating factor (G-CSF) in cancer patients. DESIGN AND METHODS: One hundred and fifty patients underwent 627 PBPC collections during the recovery phase following CT with (n = 469) or without (n = 142) G-CSF. Hemogram, CFC-assays and CD34+ cell count were performed on peripheral blood and leukaphereses products. After log transformation of the data, differences between groups were assessed with the unpaired t-test or one-way analysis of variance. RESULTS: Seventeen and two patients required 2 and 3 mobilization cycles respectively to reach our target of 15x10(4) CFU-GM/kg. In patients with lymphoma but not in those with leukemia, the yields of both CFU-GM and CD34+ cells/kg were dramatically increased when G-CSF was added to CT for mobilization. In collections primed with CT and G-CSF, better yields were obtained in patients with breast cancer or small-cell lung carcinoma (SCLC) as opposed to other solid tumors and leukemia. Among potential predictive factors of CT- and G-CSF-primed harvests, we found that the CD34+ cell count in peripheral blood (PB) was strongly correlated with both the CFU-GM and CD34+ cell yields. Except in leukemia patients, more than 1x10(6) CD34+ cells/kg were harvested when the CD34+ cell count in blood was above 20x10(6)/L. Similarly, better results were obtained in collections performed when the percentage of myeloid progenitors in blood on the day of apheresis was above 5 % or when the leukocyte count in blood was above 5x10(9)/L. INTERPRETATION AND CONCLUSIONS: A diagnosis of breast cancer or SCLC, a leukocyte count in PB of more than 5x10(9)/L, more than 5% myeloid progenitors or more than 20x10(6) CD34+ cells/L in PB were associated with higher yields of PBPC in collections mobilized with CT+G-CSF. [less ▲]Detailed reference viewed: 52 (8 ULg)
Influence of marrow erythropoietic activity on serum erythropoietin levels after autologous hematopoietic stem cell transplantation.
Beguin, Yves ; Baron, Frédéric ; Fillet, Georges
in Haematologica (1998), 83(12), 1076-81
BACKGROUND AND OBJECTIVE: Serum erythropoietin (sEpo) concentration depends primarily on the rate of renal production in response to hypoxia. However, sEpo levels increase inappropriately after ... [more ▼]
BACKGROUND AND OBJECTIVE: Serum erythropoietin (sEpo) concentration depends primarily on the rate of renal production in response to hypoxia. However, sEpo levels increase inappropriately after conditioning for autologous stem cell transplantation (ASCT) before progressively returning to adequate levels. We investigated the possible influence of erythropoietic activity on these observations. DESIGN AND METHODS: Forty patients undergoing an ASCT, 8 with bone marrow (BMT) and 32 with peripheral blood stem cells (PBSC), were separated into 3 groups. Group 1 was formed of the 8 BMT patients (median time to 1% reticulocytes: 39 days), group 2 of 16 PBSC patients with relatively slow erythroid engraftment (> or = 15 days to 1% reticulocytes, median 19 days) and group 3 of 16 PBSC patients with prompt erythroid recovery (< 15 days to 1% reticulocytes, median 13 days). Marrow erythroid activity was assessed by serum transferrin receptor levels (sTfR). Serum Epo (sEpo) levels were expressed in relation to the degree of anemia as observed/predicted (O/P) ratios of (O/P) log (sEpo). RESULTS: Serum sTfR levels decreased by more than 50% in all 3 groups after conditioning, reaching their nadir on day 7. Nadir values doubled by day 28 in group 3, day 60 in group 2, but not within 100 days in group 1. O/P sEpo ratios increased inappropriately in all 3 groups after conditioning but then declined at very differing speeds in the 3 groups. In group 1, ratios remained above 1.10 through to day 28 and above 1.00 through to day 42, before leveling off at around 1.00 thereafter. In group 2, ratios remained above 1.00 through to day 14, than decreased to a minimum of 0.89 by day 42 before returning to 1.00 by day 100. In group 3, ratios decreased to 0.84 by day 21 and remained below 0.90 thereafter. INTERPRETATION AND CONCLUSIONS: We conclude that sEpo levels are not only influenced by tissue oxygenation but also depend on the mass of erythroid precursors in the bone marrow. This may be the main explanation for the observed changes in sEpo levels during ASCT. [less ▲]Detailed reference viewed: 11 (3 ULg)
The veno-occlusive disease of the liver.
Baron, Frédéric ; Deprez, Manuel ; Beguin, Yves
in Haematologica (1997), 82(6), 718-25
BACKGROUND AND OBJECTIVE: The veno-occlusive disease of the liver (VOD) is a disorder caused by the non-thrombotic occlusion of the central veins of hepatic lobules. The clinical features are similar to ... [more ▼]
BACKGROUND AND OBJECTIVE: The veno-occlusive disease of the liver (VOD) is a disorder caused by the non-thrombotic occlusion of the central veins of hepatic lobules. The clinical features are similar to those of intrahepatic portal hypertension (unexplained weight gain, ascites, painful hepatomegaly, jaundice). In the past, this disease was rather infrequent and was linked to the absorption of toxic agents, liver irradiation or chemotherapy. However, the intensification of treatment protocols before hematopoietic stem cell transplants has considerably increased its incidence. The strategies used for its prevention and treatment remain limited in efficacy. The present review was undertaken in order to assess progress in the diagnosis and management of this severe complication in stem cell transplantation. INFORMATION SOURCES: The method used for preparing this review was an examination of 250 relevant articles or abstracts published in journals covered by Medline. STATE OF ART: Despite the progress made toward the understanding of its physiopathology and the identification of its risk factors, VOD is still one of the leading causes of morbidity and mortality during the first two months post-BMT, and therefore often constitutes a limitation for the further increment of the dose of antineoplastic drugs. This may be explained by the difficulty in making an early diagnosis of this problem, at a time when therapeutic intervention may be more effective, and, on the other hand, the lack of a well-established prevention and treatment approach for patients with VOD. PERSPECTIVES AND CONCLUSIONS: New diagnostic procedures, such as laparoscopic liver biopsy, and new therapeutic approaches, such as transjugular intrahepatic portosystemic shunting (TIPS) or defibrotide, are now being evaluated. However, additional studies will be needed to determine the most appropriate therapy for each VOD patient depending on the severity of the disease. [less ▲]Detailed reference viewed: 14 (3 ULg)
Prediction of response to recombinant human erythropoietin (rHuEpo) in anemia of malignancy.
; ; et al
in Haematologica (1996), 81(5), 434-41
BACKGROUND: Since only a portion of anemic patients outside the uremia setting benefit from erythropoietin treatment, a reliable means of predicting potential responders and nonresponders would be very ... [more ▼]
BACKGROUND: Since only a portion of anemic patients outside the uremia setting benefit from erythropoietin treatment, a reliable means of predicting potential responders and nonresponders would be very useful. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of 58 patients with refractory anemia associated with various malignant disorders who had been treated with subcutaneous rHuEpo. The starting rHuEpo dose was 375 U/kg/week for 4 weeks, and was increased to 750 U/kg/week for another 4 weeks if no response was observed. Response was defined as a Hb increase > or = 2 g/dL with no need for blood transfusion. We examined the value of various laboratory parameters (baseline levels, 2-week and 4-week changes) as predictors of response. Endogenous erythropoietin production was evaluated by its serum level and erythroid activity was assessed through reticulocyte count and circulating transferrin receptor. RESULTS: Forty-eight individuals were evaluable, 58% of whom responded to rHuEpo within 8 weeks. Multiple regression analysis showed that 53% of the variation in the 8-week Hb concentration was explained by variations in baseline serum erythropoietin and the 2-week change in serum transferrin receptor (p < 0.001). Based on these two parameters, response prediction in individual patients would have resulted in a sensitivity of 96%, a specificity of 79% and an overall accuracy of 88%. In addition, 58% of the variation in the 8-week Hb was explained by variations in the 4-week changes in Hb and reticulocyte count (p < 0.001). Utilizing these latter parameters and baseline serum erythropoietin, response prediction in individual patients would have resulted in a sensitivity of 92%, a specificity of 82% and an overall accuracy of 88%. CONCLUSIONS: This retrospective analysis suggests that response to rHuEpo can be reasonably predicted by pretreatment serum erythropoietin together with early changes in simple laboratory parameters. [less ▲]Detailed reference viewed: 12 (0 ULg)
Pure red cell aplasia following peripheral stem cell transplantation: complete response to a short course of high-dose recombinant human erythropoietin.
; ; Beguin, Yves et al
in Haematologica (1994), 79(5), 456-9
We studied a patient who developed pure red cell aplasia (PRCA) following peripheral stem cell transplantation for non-Hodgkin lymphoma. Serum erythropoietin was appropriate for the degree of anemia ... [more ▼]
We studied a patient who developed pure red cell aplasia (PRCA) following peripheral stem cell transplantation for non-Hodgkin lymphoma. Serum erythropoietin was appropriate for the degree of anemia. Corticosteroid treatment was ineffective. Four months after transplantation rHuEpo was administered subcutaneously at a dose of 150 U/Kg per day, five days a week for 8 weeks. Treatment induced an erythropoietic response and corrected anemia. Response was maintained following discontinuation of rHuEpo. This study and previous reports indicate that high doses of rHuEpo given over a short time can resolve PRCA following autologous or allogeneic stem cell transplantation. [less ▲]Detailed reference viewed: 18 (0 ULg)
The soluble transferrin receptor: biological aspects and clinical usefulness as quantitative measure of erythropoiesis.
in Haematologica (1992), 77(1), 1-10
Iron transport in plasma is carried out by transferrin, which donates iron to cells through interaction with a specific membrane receptor. In this review, we summarize the current knowledge on the ... [more ▼]
Iron transport in plasma is carried out by transferrin, which donates iron to cells through interaction with a specific membrane receptor. In this review, we summarize the current knowledge on the structure, intracellular cycle, distribution, and regulation of the tissue transferrin receptor. A soluble form of the transferrin receptor has been identified in animal and human serum. We review the molecular form and origin of the soluble receptor, its dosage in normal serum and its relationship with erythropoiesis, iron status, and cancer. Lastly, we discuss the clinical usefulness of the soluble transferrin receptor for the quantitative determination of marrow erythropoietic activity. [less ▲]Detailed reference viewed: 17 (1 ULg)
Evaluation of erythroid marrow response to recombinant human erythropoietin in patients with cancer anaemia.
; Beguin, Yves ; et al
in Haematologica (1992), 77(6), 494-501
BACKGROUND. Anaemia is a frequent finding in patients with cancer and may be due to different causes, including blunted erythropoietin production. MATERIALS AND METHODS. In a pilot study, we administered ... [more ▼]
BACKGROUND. Anaemia is a frequent finding in patients with cancer and may be due to different causes, including blunted erythropoietin production. MATERIALS AND METHODS. In a pilot study, we administered recombinant human erythropoietin (rHuEPO) to twelve patients with solid tumours and secondary anaemia. rHuEPO was given subcutaneously 5 d per week at escalating doses (75 to 150 U/kg per day): the aim of treatment was a Hb level > or = 10 g/dl without blood transfusion. We evaluated endogenous EPO production through serum EPO levels and erythroid marrow activity by means of serum transferrin receptor (TfR). RESULTS. Six out of 12 subjects had defective endogenous EPO production. All patients but two responded to treatment with steady increases in Hb levels above 10 g/dl, and the median dose of rHuEPO required for correction of anaemia was 75 U/kg. Response was associated with an early increase in serum TfR. Six patients developed functional iron deficiency and required iron supplementation to obtain response. Treatment improved functional ability in 4/10 responders. CONCLUSIONS. Subcutaneous rHuEPO can stimulate erythroid marrow activity in cancer anaemia, even in patients with advanced disease, and marrow response can be adequately monitored by serum TfR. Functional iron deficiency as a cause of nonresponse to rHuEPO is frequent in these patients and may require parenteral iron administration. Although erythropoietin can improve the anaemia of cancer, the decision to treat should be individualised for each patient, looking more at the quality of life and cost-effectiveness than at cosmetic increases in the haemoglobin level. [less ▲]Detailed reference viewed: 5 (1 ULg)