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: 12 (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: 11 (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: 15 (0 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: 4 (0 ULg)