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Biomedical subjects

Y Beguin

Publications and source records attributed to Y Beguin.

139 records · Page 8Linked to original sources

Serum zinc and copper as prognostic factors in acute nonlymphocytic leukemia.

A total of 44 patients were treated with intensive induction chemotherapy for acute nonlymphocytic leukemia (ANLL). A complete remission (CR) was obtained in 29/44 (66%) patients. Serum zinc (Zn) and copper (Cu) were studied as possible prognostic factors in the determination of the chance of a patient attaining remission. Pretreatment Zn was higher in patients attaining a remission (0.99 +/- 0.05 microgram/ml) than in patients failing to attain a CR (0.78 +/- 0.06 microgram/ml) (P = 0.0216). There was no further difference between the two groups during aplasia. However, when response to treatment was evaluated about day 28, the difference reappeared: 1.06 +/- 0.05 microgram/ml for CR patients vs 0.77 +/- 0.07 microgram/ml for failures (p = 0.0012). Pretreatment Cu was higher in responding (1.44 +/- 0.07 microgram/ml) than in nonresponding (1.06 +/- 0.05 microgram/ml) patients (p = 0.0002). The difference between the two groups remained highly significant at days 7, 14, 21, and 28. At the time of response evaluation, the values were 1.46 +/- 0.05 microgram/ml for CR patients vs 1.19 +/- 0.08 microgram/ml for non-CR patients (P = 0.0070). We conclude that the measurement of serum Zn and Cu may be helpful in the prediction of response to chemotherapy in patients treated for ANLL.

Acute Disease↗

Plasmacytoma of the thyroid: a case report, a study with use of the immunoperoxidase technique, and a review of the literature.

A case of solitary plasmacytoma of the thyroid is reported. A monoclonal component (IgG lambda) was identified in the serum of the patient and disappeared after total thyroidectomy and radiotherapy. The use of the immunoperoxidase technique on thyroid, bone marrow, and lymph node specimens allowed us to demonstrate the production of IgG lambda by the tumor, and to rule out the possibility of multiple myeloma. Previously reported cases are reviewed (15 cases). The diagnostic criteria, the association with thyroiditis, and the treatment of this rare disorder are discussed.

Bone Marrow↗

Treatment of acute nonlymphocytic leukemia in young and elderly patients.

Among 95 consecutive patients with acute nonlymphocytic leukemia (ANLL), 61 were treated with a high-dose chemotherapeutic induction regimen consisting of daunorubicin, vincristine, and cytosine arabinoside (DOA). The complete remission (CR) rate was 66%. Although young patients responded better than older patients, only sex was found to be of prognostic significance for achieving CR (84% CR in men versus 47% in women, P less than 0.005, independent of age). Patients in CR received consolidation, monthly maintenance therapy, and late intensification for a period of 2 years. Median remission duration was 57 weeks and median survival, 93 weeks. Projected CR rate at 5 years was 30%. CR and survival duration were significantly longer in patients 40 to 60 years old when compared with younger and older patients (P = 0.023). They were also longer in male than in female patients (P = 0.018), but this may be due to an effect of age. In the 34 patients who did not receive DOA treatment because of age or poor clinical conditions, there was no survival beyond 57 weeks, except in a 73-year-old woman who reached a spontaneous remission during acute infection. ANLL characteristics at presentation revealed a tendency toward a smaller tumor mass (P less than 0.05) and rarer Auer rods present (P = 0.03) with increasing age. Features and treatment of ANLL in elderly patients are discussed in view of the poor results obtained with conservative management.

Acute Disease↗

Monitoring of erythropoiesis by the serum transferrin receptor and erythropoietin.

Virtually all cells have transferrin receptors (a transmembrane glycoprotein) on their surface but in a normal adult, 80% of them are in the erythroid marrow. Some of them are lost into the circulation where they can be measured by immuno-assays. A direct and highly significant correlation exists between serum transferrin receptor level and erythron transferrin uptake in humans. The measurement of serum transferrin receptor has wide clinical applications for the quantitation of erythropoiesis. It can be used to study erythropoiesis in situations in which ferrokinetics is not acceptable such as pregnancy. It is particularly useful for serial studies, e.i., for monitoring the recovery of erythropoiesis after stem cell transplantation or after treatment with erythropoietin. Combined with the determination of serum erythropoietin, both evaluated in relation to the degree of anemia, they provide a physiological approach to the diagnosis of anemia. Thus, the simultaneous determination of hematocrit, reticulocytes, serum transferrin receptor and serum erythropoietin has high discriminatory value in distinguishing between a defect in erythroid proliferation, maturation or red cell survival. It is also particularly useful for detecting the presence of multiple mechanisms of anemia in the same patient.

Anemia, Iron-Deficiency↗

Outpatient and home parenteral antibiotic therapy (OHPAT) in low-risk febrile neutropenia: consensus statement of a Belgian panel.

Febrile neutropenia requires adequate antibiotic treatment. A subgroup of patients are only at low risk for complications and could be treated at home/as outpatients (OHPAT) after a short initial admission for work up. This position paper by a Belgian panel of experts presents criteria defining low-risk in febrile neutropenia, gives an overview of the existing experience and examines the present obstacles to a more widespread use of OHPAT in this country.

Anti-Bacterial Agents↗

Minitransplants: allogeneic stem cell transplantation with reduced toxicity.

Allogeneic hematopoietic stem cell transplantation (HSCT) is used for the treatment of selected hematological malignancies. Its curative potential is based on two very different mechanisms, involving the conditioning regimen and the graft-versus-host reactions, respectively. The high-dose chemo-radiotherapy conditioning regimen is aimed at destroying tumor cells, ablating the host immune system (to prevent rejection) and eliminating the host bone marrow (to "make space" for donor stem cells). However, the definitive eradication of tumor cells is also largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger (< 55 years) and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols based on a two step approach: first the use of immunosuppressive (but nonmyeloablative) conditioning regimens providing sufficient immunosuppression to achieve engraftment of allogeneic hematopoietic stem cells and, in a second step, destruction of malignant cells by the GVL effect. These transplants are called nonmyeloablative HSCT or reduced-conditioning HSCT or minitransplants. Preliminary results show that minitransplants are feasible with a relatively low transplant-related mortality (TRM) even in patients up to 70 years. In addition, strong anti-tumor responses are observed in several hematological malignancies as well as in some patients with renal cell carcinoma. As the benefits of minitransplants over alternative forms of treatment remain to be demonstrated, this strategy should be restricted to patients included in clinical trials.

Adult↗

Primary amyloidosis (AL) as a cause of nephrotic syndrome.

AL amyloidosis is a rare systemic disease resulting from tissue accumulation of amyloid fibrils derived from monoclonal immunoglobulin light chains. It can disrupt the tissue architecture and consequently cause organ dysfunction. The prognosis is poor with a median survival of 13 months in untreated patients. By illustrating the case of a patient whose AL amyloidosis was detected after presenting a nephrotic syndrome, the characteristics of the disease are reviewed as well as diagnostic criteria and current available therapeutics.

Amyloidosis↗

Evaluation of erythroid marrow response to recombinant human erythropoietin in patients with cancer anaemia.

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.

Aged↗

The soluble transferrin receptor: biological aspects and clinical usefulness as quantitative measure of erythropoiesis.

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.

Anemia↗

Pure red cell aplasia following peripheral stem cell transplantation: complete response to a short course of high-dose recombinant human erythropoietin.

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.

Dose-Response Relationship, Drug↗

Prediction of response to recombinant human erythropoietin (rHuEpo) in anemia of malignancy.

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.

Anemia↗

The veno-occlusive disease of the liver.

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.

Bone Marrow Transplantation↗