A moderate transfusion regimen may reduce iron loading in beta-thalassemia major without producing excessive expansion of erythropoiesis.
; ; et al
in Transfusion (1997), 37(2), 135-40
BACKGROUND: Hypertransfusion with a baseline hemoglobin of 10 to 12 g per dL is still considered by many to be the mainstay of conservative therapy for beta-thalassemia major. However, this regimen is ... [more ▼]
BACKGROUND: Hypertransfusion with a baseline hemoglobin of 10 to 12 g per dL is still considered by many to be the mainstay of conservative therapy for beta-thalassemia major. However, this regimen is frequently associated with manifestations of transfusion iron overload, despite regular chelation therapy with subcutaneous desferoxamine. STUDY DESIGN AND METHODS: To verify whether a transfusion regimen with a target pretransfusion hemoglobin level between 9 and 10 g per dL can allow a significant reduction in blood consumption, while still effectively suppressing erythropoiesis, the records were reviewed of 32 beta-thalassemia major patients, who were maintained at a pretransfusion hemoglobin of 11.3 +/- 0.5 g per dL between 1981 and 1986. These patients were switched at the beginning of 1987 to a transfusion regimen with pretransfusion hemoglobin of 9.4 +/- 0.4 g per dL. The degree of erythroid marrow activity was evaluated in these patients and in 32 subjects with beta-thalassemia intermedia through the simple measurement of serum transferrin receptor. RESULTS: After the adoption of the moderate transfusion regimen, transfusion requirements decreased from 137 +/- 26 to 104 +/- 23 mL per kg per year of red cells (p < 0.0001), and mean serum ferritin decreased from 2448 +/- 1515 to 1187 +/- 816 micrograms per L (p < 0.0001), with one-half of patients achieving serum ferritin levels lower than 1000 micrograms per L. The proportion of patients having spontaneous pubertal development increased significantly (p < 0.01), as a result of less iron-related gonadotropin insufficiency. At the lower pretransfusion hemoglobin, erythroid marrow activity did not exceed two to three times normal levels in most subjects. CONCLUSION: As compared with hypertransfusion, moderate transfusion may allow more effective prevention of iron loading, with higher likelihood of spontaneous pubertal development and without producing excessive expansion of erythropoiesis. [less ▲]Detailed reference viewed: 29 (2 ULg)
Anaemia of lung cancer is due to impaired erythroid marrow response to erythropoietin stimulation as well as relative inadequacy of erythropoietin production.
; R'Zik, Samir ; Fillet, Georges et al
in British Journal of Haematology (1997), 97(2), 297-9
Many studies have been done in order to elucidate the pathogenesis of the anaemia of chronic disorders accompanying cancer, with conflicting results. This is probably due to the heterogeneity of the ... [more ▼]
Many studies have been done in order to elucidate the pathogenesis of the anaemia of chronic disorders accompanying cancer, with conflicting results. This is probably due to the heterogeneity of the patient population selected for these studies (many patients treated by chemotherapy). To avoid this pitfall, in this study a very homogenous group of chemotherapy and radiotherapy-naive patients with lung cancer were selected. Serum erythropoietin and soluble transferrin receptor measurements suggested that the anaemia of non-treated lung cancer is mainly due to an impaired erythroid marrow response to erythropoietin stimulation. However, a relative inadequacy of erythropoietin production may also contribute. [less ▲]Detailed reference viewed: 19 (3 ULg)
Complications hepatiques de la chimiotherapie. De la cytolyse banale a la maladie veino-occlusive du foie.
Baron, Frédéric ; Beguin, Yves
in Revue Médicale de Liège (1997), 52(2), 93-7Detailed reference viewed: 108 (5 ULg)
Use of recombinant human erythropoietin after allogeneic bone marrow transplantation
; Beguin, Yves
in Erythropoiesis (1997), 8Detailed reference viewed: 7 (2 ULg)
Complications hépatiques de la chimiothérapie : de la cytolyse banale à la maladie veino-occlusive du foie
Baron, Frédéric ; Beguin, Yves
in Médecine & Chirurgie Digestives (1997), 26Detailed reference viewed: 76 (3 ULg)
Mechanisms of cancer-related anemia and rationale for erythropoietin treatment
in Cancer Biotherapy (1997), 1Detailed reference viewed: 3 (2 ULg)
Actualités thérapeutiques dans la thrombocytémie essentielle
; ; Beguin, Yves et al
in Médecine et Hygiène (1996), 54
Essential thrombocythemia is a myeloproliferative disorder affecting megakaryocyte and is characterized by frequent thrombotic or hemorrhagic complications. In young patients, the optimal management of ... [more ▼]
Essential thrombocythemia is a myeloproliferative disorder affecting megakaryocyte and is characterized by frequent thrombotic or hemorrhagic complications. In young patients, the optimal management of thrombocythaemia is controversial. Since th relationship of thrombosis and hemorrhage to platelet counts is not demonstrated, ther is no clear inidcation for using drugs capable of lowering platelet counts in young asymptomatic subjects. However, treatment should be offered to patients with a definite high risk of major or life-threatening hemostatic complications. The present paper reviews the incidence and risk factors for thrombotic complications and the use of medications inhibiting platelet production. [less ▲]Detailed reference viewed: 91 (2 ULg)
Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis.
; ; et al
in Blood (1996), 87(11), 4824-30
Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear ... [more ▼]
Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released. [less ▲]Detailed reference viewed: 18 (1 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: 14 (0 ULg)
Erythropoietin and the anemia of cancer.
in Acta Clinica Belgica (1996), 51(1), 36-52
The pathogenesis of the anemia of cancer involves the combination of a shortened erythrocyte survival in circulation with the failure of bone marrow to increase red cell production in compensation ... [more ▼]
The pathogenesis of the anemia of cancer involves the combination of a shortened erythrocyte survival in circulation with the failure of bone marrow to increase red cell production in compensation. Inappropriate red cell production is itself related to a conjunction of factors, including impaired availability of reticuloendothelial storage iron, inadequate erythropoietin (Epo) response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. Many of these cytokines may interfere with erythropoietin production by the kidney. Consequently inadequate serum erythropoietin levels are often encountered in cancer patients, though more frequently in those with solid tumors or multiple myeloma than in those with other hematologic malignancies. There is little evidence supporting a negative impact of chemotherapy, including cisplatin, on erythropoietin production. Rather, chemotherapy usually causes a transient elevation of serum Epo. Red cell transfusions are often administered to cancer patients, possibly resulting, among other deleterious effects, in enhancement of tumor growth. Recombinant human erythropoietin (rHuEpo) has thus been proposed as an alternative. RHuEpo has been shown to be safe and effective in correcting the anemia of cancer and reducing the need for transfusions. The response rate is as good in hematologic malignancies as in solid tumors, but it is extremely poor in those with myelodysplastic syndromes. The effect of rHuEpo does not differ among patients receiving or not receiving chemotherapy, including cisplatin. The probability of response is also similar in patients with adequate or inappropriate erythropoietin production before therapy, although the doses used are usually 2 to 3 times higher than in renal failure patients. [less ▲]Detailed reference viewed: 21 (2 ULg)
Serum erythropoietin in chronic lymphocytic leukaemia.
Beguin, Yves ; ; et al
in British Journal of Haematology (1996), 93(1), 154-6
Anaemia is a frequent complication of advanced chronic lymphocytic leukaemia (CLL) and several cytokines known to inhibit erythropoietin (Epo) formation are produced by CLL B cells. Therefore we measured ... [more ▼]
Anaemia is a frequent complication of advanced chronic lymphocytic leukaemia (CLL) and several cytokines known to inhibit erythropoietin (Epo) formation are produced by CLL B cells. Therefore we measured serum Epo levels in 47 CLL patients to determine whether Epo was a significant factor in the development of their anaemia. Epo levels were increased compared to normal individuals and this elevation appeared adequate for the degree of anaemia. The slope of the regression of Epo versus haemoglobin (Hb) was similar to that of a reference group. Serum transferrin receptor (sTfR) levels were also appropriately elevated for the degree of anaemia and correlated with serum Epo. Advanced stage was not associated with reduction of Epo production but diminished erythropoietic activity was observed in several patients. The results indicate that anaemia in CLL is not characterized by inadequate Epo production. [less ▲]Detailed reference viewed: 9 (5 ULg)
Spontaneous complete remission and recovery of donor haemopoiesis without GVHD after relapse and apparent marrow graft rejection in poor-prognosis myelodysplastic syndrome.
Beguin, Yves ; Collignon, Jacques ; et al
in British Journal of Haematology (1996), 94(3), 507-9
We report a patient with poor-prognosis myelodysplastic syndrome (MDS) after successful treatment of lymphoma, who was given an allogeneic BMT, engrafted and achieved complete remission, but later had a ... [more ▼]
We report a patient with poor-prognosis myelodysplastic syndrome (MDS) after successful treatment of lymphoma, who was given an allogeneic BMT, engrafted and achieved complete remission, but later had a relapse of his MDS with complete disappearance of donor haemopoiesis. After two episodes of CMV pneumonia and continued prophylactic use of ganciclovir thereafter, he experienced a spontaneous complete disappearance of all signs of MDS, including myelofibrosis, and a complete return to donor haemopoiesis. This case is the first one to suggest a graft-versus-leukaemia effect (GVL) in MDS patients. It depicts the complex relationship between GVL, graft-versus-host disease (GVHD) and graft rejection. It could also constitute a clinical illustration of the possible antileukaemic effect of CMV infection and its treatment with ganciclovir. [less ▲]Detailed reference viewed: 24 (4 ULg)
Confrontation anatomo-clinique. Purpura thrombocytopenique thrombotique dans le decours d'une greffe de moelle.
Pasquasy, Véronique ; Delvenne, Philippe ; Thiry, Albert et al
in Revue Médicale de Liège (1996), 51(11), 714-7Detailed reference viewed: 29 (13 ULg)
La greffe de cellules souches hematopoietiques (greffe de moelle osseuse"): indications, modalites et risques."
in Revue Médicale de Liège (1996), 51(4), 270-5Detailed reference viewed: 46 (8 ULg)
Biology and clinical uses of erythropoietin in infants and children
in International Journal of Pediatric Hematology/Oncology (1995), 2Detailed reference viewed: 17 (5 ULg)
Quantitative assessment of erythropoiesis in haemodialysis patients demonstrates gradual expansion of erythroblasts during constant treatment with recombinant human erythropoietin.
Beguin, Yves ; ; R'Zik, Samir et al
in British Journal of Haematology (1995), 89(1), 17-23
Recombinant human erythropoietin (rHuEpo) has been shown to be effective in correcting the anaemia of chronic renal failure. It has been reported that reticulocytes as well as erythroid progenitors ... [more ▼]
Recombinant human erythropoietin (rHuEpo) has been shown to be effective in correcting the anaemia of chronic renal failure. It has been reported that reticulocytes as well as erythroid progenitors increase within 1-2 weeks, with no further elevation beyond this time interval. However, the erythroblast pool is quantitatively the most important compartment of erythropoiesis, and the rate, extent and duration of the expansion of erythropoietic activity in response to rHuEpo is not known. Treatment with rHuEpo was given to 64 patients i.v. thrice weekly after haemodialysis. The effect of rHuEpo was obvious from the early elevation of reticulocyte counts, but much of this increase was due to a rapid output of shift reticulocytes which levelled off after a few weeks. Serum transferrin receptor (TfR), a quantitative measure of erythropoiesis, increased progressively over 6 weeks to reach a plateau phase at about twice baseline values. The Hct increased progressively and continued to rise steadily after the TfR plateau was reached. The speed and extent of the expansion of erythropoietic activity correlated with the later haematological response to rHuEpo. When rHuEpo was discontinued, erythropoietic activity returned progressively to baseline values, to rise again gradually when treatment was resumed. Part of the Hct increase was also due to haemoconcentration. The results indicate that changes in the various erythroid compartments vary considerably in intensity and speed, and that the erythroblast compartment in particular is slow to respond to modifications in the erythropoietin stimulus. [less ▲]Detailed reference viewed: 30 (2 ULg)
Relationship between transfusion regimen and suppression of erythropoiesis in beta-thalassaemia major.
; ; et al
in British Journal of Haematology (1995), 89(3), 473-8
In the management of beta-thalassaemia major, different transfusion schemes are employed with baseline haemoglobin levels ranging from 8 to over 12 g/dl. We studied the relationship between transfusion ... [more ▼]
In the management of beta-thalassaemia major, different transfusion schemes are employed with baseline haemoglobin levels ranging from 8 to over 12 g/dl. We studied the relationship between transfusion regimen and suppression of erythropoiesis in 52 patients with beta-thalassaemia major whose mean pretransfusion haemoglobin levels ranged from 8.6 to 10.9 g/dl. Multiple, regression analysis showed that serum transferrin receptor was the parameter more closely related to mean pretransfusion haemoglobin (r = -0.77, P < 0.001). As measured through serum transferrin receptor, erythroid activity was 1-2 times normal for pretransfusion haemoglobin levels between 10 and 11 g/dl. 1-4 times normal for levels from 9 to 10 g/dl, and 2-6 times normal for levels from 8.6 to 9 g/dl. Mean pretransfusion haemoglobin was also inversely related to serum erythropoietin (r = -0.72, P < 0.001), whereas it showed no or a weak relationship with Hb F, reticulocyte count, or circulating nucleated red cell count. This study suggests that serum transferrin receptor is a reliable indicator of suppression of erythropoiesis in beta-thalassaemia major. On the basis of our findings, pretransfusion haemoglobin values of < or = 9 g/dl should be adopted with caution, because these levels can be associated with an insufficient inhibition of erythroid marrow expansion. However, a transfusion programme, with a baseline haemoglobin of 9-10 g/dl, may provide enough suppression of erythropoiesis and allow a reduction in blood consumption as compared with the classic hyper- or supertransfusion schemes. Since fixed haemoglobin levels may not be the best target for transfusion treatment in all thalassaemic patients, assay of serum transferrin receptor may be helpful for individualizing the transfusion regimens. [less ▲]Detailed reference viewed: 13 (2 ULg)
Erythropoiesis and erythropoietin in multiple myeloma.
in Leukemia & Lymphoma (1995), 18(5-6), 413-21
In this review, the pathophysiology and treatment of the anemia of multiple myeloma will be examined. While the anemia of cancer has multiple causes, an important component is labeled the "anemia of ... [more ▼]
In this review, the pathophysiology and treatment of the anemia of multiple myeloma will be examined. While the anemia of cancer has multiple causes, an important component is labeled the "anemia of chronic disease" which is characterized by the combination of a shortened erythrocyte survival with failure of the bone marrow to increase red cell production in compensation. Depressed erythropoiesis is itself related to a combination of factors, including impaired availability of storage iron, inadequate erythropoietin response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. These cytokines are involved in the retention of iron in the reticuloendothelial system, gastrointestinal tract and hepatocytes, may interfere with erythropoietin production by the kidney, and may exert direct inhibitory effects on erythroid precursors. While overproduction of several such cytokines, including IL-6, IL-1 and TNF-alpha, has been definitely demonstrated in multiple myeloma patients, it is still unclear whether they are directly involved in the pathogenesis of the anemia which develops. Although several mechanisms, such as hemodilution, bleeding, and decreased red cell survival operate, the anemia is mostly caused by defective erythropoietic activity. This in turn is partly explained by inadequate erythropoietin (Epo) production even in some patients without renal impairment. Based on measurements of serum erythropoietin and transferrin receptor, the distinction between marrow unresponsiveness to normal Epo stimulation and deficient Epo production is important for the treatment of the anemia of multiple myeloma with recombinant human Epo. Higher doses would probably be necessary if adequate Epo production is present, whereas only replacement therapy with lower doses may be sufficient when Epo production has been shown to be inappropriate. [less ▲]Detailed reference viewed: 31 (3 ULg)
Hepatic rejection after orthotopic liver transplantation for hepatic veno-occlusive disease or graft-versus-host disease following bone marrow transplantation.
; Honore, Pierre ; Damas, Pierre et al
in Transplantation (1995), 60(1), 106-9Detailed reference viewed: 19 (5 ULg)
Pharma clinics. Comment je traite ... une anemie (3e partie).
in Revue Médicale de Liège (1995), 50(12), 497-8Detailed reference viewed: 28 (6 ULg)