Effect of recombinant human erythropoietin combined with granulocyte/ macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group.

This randomized, placebo-controlled trial was designed to assess the efficacy and safety of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patients with myelodysplastic syndrome. Sixty-six patients were enrolled according to the following French-American-British classification: refractory anemia (20), refractory anemia with excess blasts (35), refractory anemia with ringed sideroblasts (9), and refractory anemia with excess blasts in transformation (2). Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) and randomized, in a 2:1 ratio, to either GM-CSF (0.3-5.0 microg/kg.d) + epoetin alfa (150 IU/kg 3 times/wk) or GM-CSF (0.3-5.0 microg/kg.d) + placebo (3 times/wk). The mean neutrophil count rose from 948 to 3831 during treatment with GM-CSF +/- epoetin alfa. Hemoglobin response (increase greater than or equal to 2 g/dL, unrelated to transfusion) occurred in 4 of 45 (9%) patients in the GM-CSF + epoetin alfa group compared with 1 of 21 (5%) patients with GM-CSF + placebo group (P = NS). Percentages of patients in the epoetin alfa and the placebo groups requiring transfusions of red blood cells were 60% and 92%, respectively, for the low-endogenous erythropoietin patients and 95% and 89% for the high-endogenous erythropoietin patients (P = NS). Similarly, the average numbers of units of red blood cells transfused during the 12-week study in the epoetin alfa and the placebo groups were 5.9 and 9.5, respectively, in the low-endogenous erythropoietin patients and 9.7 and 8.6 in the high-endogenous erythropoietin patients (P = NS). GM-CSF +/- epoetin alfa had no effect on mean platelet count. Treatment was well tolerated in most patients, though 10 withdrew from the study for reasons related predominantly to GM-CSF toxicity. (Blood. 2000;95:1175-1179)

The predictive power of baseline hemoglobin for transfusion risk in surgery patients.

Preoperative hemoglobin concentration may be an important predictor of transfusion risk in surgical procedures with significant expected blood loss. Contemporary studies investigating transfusion risk with regard to the relationship between perioperative administration of Epoetin alfa and baseline hemoglobin provide data to test this hypothesis. The predictive power of seven preoperative variables (hemoglobin concentration, age, erythropoietin level, ferritin concentration, serum iron, total iron-binding capacity, and predicted blood volume) on transfusion risk was examined via retrospective logistic regression analysis of 276 orthopedic surgical patients. In the two studies used to perform the regression analysis, patients were treated daily with either Epoetin alfa or placebo. Based on the retrospective analyses, a prospective study was conducted to validate the hypothesis. Of the seven variables evaluated, baseline hemoglobin concentration and predicted blood volume were significantly predictive of transfusion risk in both Epoetin alfa- and placebo-treated patients. Further, an inverse correlation between hemoglobin concentration and transfusion risk was demonstrated in placebo-treated patients. Placebo-treated patients with hemoglobin > 10 to < or = 13 g/dL had an approximately twofold greater risk of transfusion than patients with hemoglobin > 13 g/dL. In contrast to placebo treatment, Epoetin alfa significantly reduced transfusion risk in patients with hemoglobin > 10 to < or = 13 g/dL. Baseline hemoglobin concentration is an excellent predictor of transfusion risk in orthopedic surgical patients. As a result, hemoglobin testing should be considered a part of routine preoperative testing for orthopedic surgical patients.

Recombinant human erythropoietin therapy for anemic cancer patients receiving cisplatin chemotherapy.

PURPOSE: To assess whether the administration of recombinant human erythropoietin (r-HuEPO) would increase the hematocrit, reduce the requirement for transfusion, and improve the quality of life in anemic cancer patients receiving myelosuppressive, cisplatin-based chemotherapy. PATIENTS AND METHODS: One hundred thirty-two anemic cancer patients receiving cyclic, cisplatin-containing, myelosuppressive chemotherapy were evaluated. Patients received either r-HuEPO (150 U/kg) or placebo, subcutaneously, three times a week for 3 months. Responses were assessed by measuring changes in hemoglobin/hematocrit, transfusion requirement, and quality of life. RESULTS: The mean hematocrit increased by 6.0 percentage points in the r-HuEPO group versus 1.3 in the placebo group. A decrease in transfusion requirement did not reach significance over all 3 months, but there was a significant reduction in the percentage of patients transfused in the second and third months (27% r-HuEPO vs. 56% placebo) and a trend toward reduction in the mean total number of units transfused (1.20 units r-HuEPO vs. 2.02 units placebo), suggesting a lag of 1 month before r-HuEPO can affect the transfusion requirement. Pretreatment serum erythropoietin levels were lower in responders than in nonresponders (73.5 IU/L and 86.3 IU/L means, respectively). However, the magnitude of this difference was not helpful in defining which patients were likely to respond. There was a significant improvement in overall quality of life between the two treatment arms in favor of the r-HuEPO-treated group. There were no significant adverse effects associated with r-HuEPO. CONCLUSIONS: r-HuEPO is safe and can cause a significant improvement in the hematocrit and quality of life of anemic cancer patients receiving myelosuppressive, cisplatin-based chemotherapy. After 1 month of r-HuEPO, there is also a reduction in transfusion requirement.

Effects of heteroscedasticity upon certain analyses when regression lines are not parallel.

The two sample analysis of covariance model is considered where the regression lines are found not to be parallel. There are two analyses often utilized in this case. One is to obtain a standard confidence interval for the covariate value where the two lines intersect, and the other is to find a simultaneous confidence region for the difference between the regression lines. The asymptotic robustness to heteroscedasticity of the regressions' errors of the coverage probability of each of these two confidence procedures is considered. When the sample sizes are approximately equal, and the covariate means and the covariate variances are similar between the samples, the unequal regression variances are shown to have little effect on the asymptotic coverage probabilities of these two confidence procedures. Discussions concerning the effects of unequal sample sizes and inequitably distributed covariate values are also presented. These results are illustrated in application to a clinical trial of recombinant human erythropoetin versus placebo to treat patients with anemia secondary to advanced cancer, who were not receiving chemotherapy.

The impact of prenatal care on the outcome of pregnancy.

In a 12-months' prospective project all women delivering at the Soroka Medical Center, Beer-Sheba, Israel, were studied with regard to the type of prenatal care (P.C.) and the outcome of pregnancy. The Soroka Medical Center is the sole medical facility providing obstetric and neonatal services to the 300,000 inhabitants of the region. Prenatal care is delivered by a uniform network of 70 community-based stations. The availability, type and quality of services were uniform for all women and were not altered throughout the study period. The project encompassed 7308 deliveries. 2154 Bedouin women were excluded in order to avoid possible bias due to cultural and genetic characteristics. Data regarding 5154 Jewish women were analysed. Perinatal mortality was inversely proportional to the number of prenatal contacts. The uncorrected mortality rates were 12.7% in women entirely lacking P.C. and 6.2%, 1.9% and 1.0% in patients who had 1-6, 7-10 and 11 or more prenatal contacts respectively. The low-birthweight rate was significantly increased in women lacking prenatal care (22.8%) or having rudimentary care (17.4%) as compared to those who had 11 or more prenatal contacts with medical personnel (5.9%). Prenatal care reduced neonatal morbidity as expressed by the length of hospitalization, the frequency of infants with multiple diagnoses and the incidence of specific pathologies such as respiratory distress syndrome, light for dates and asphyxia. The incidence of some complications of pregnancy (abruptio placentae, premature labor, PROM) was significantly increased in women lacking P.C. or having inadequate P.C. (1-6 prenatal contacts). Moreover, lack of prenatal care was clearly connected with high-risk delivery, thus increasing the danger to the baby. It is suggested that many adverse effects of various socio-economic, genetic and general health factors may be diminished by proper prenatal care coupled with adequate obstetric and neonatal services.

Prognostic factors in polymyositis/dermatomyositis. A computer-assisted analysis of ninety-two cases.

An effort was made to identify all patients with polymyositis/dermatomyositis (PM/DM) admitted to hospitals in Israel from 1956-1976. The diagnosis of PM/DM was retrospectively reviewed in 92 (46 definite, 26 probable, and 20 possible) cases. The most common complaints and physical findings in the course of the disease were muscle weakness (86 patients), rash (53 patients), arthritis or arthralgia (39 patients), and dysphagia (35 patients). Elevated serum aldolase levels were found in 64% of the patients for whom data were available; 92% had abnormal electromyogram results, and 60.9% had muscle histopathology consistent with PM/DM. Malignancy was diagnosed in 13 patients. Malignancy, ischemic heart disease, and pulmonary complications were the most common causes of death. The actuarial survival curve was heterogeneous, with an accelerated mortality during the first year after diagnosis and a slower mortality during the following 7 years. Independent unfavorable prognostic signs were: failure to induce remission, leukocytosis, fever, older age, a shorter disease history, and dysphagia.