vitamin-b-12 and Hodgkin-Disease

Topics: Blood Platelets; Bone Marrow; Clinical Competence; Erythrocytes; Ferritins; Gallium Radioisotopes; Granulocytes; Hematology; Hodgkin Disease; Humans; Isotope Labeling; Lymphoma; Nuclear Medicine; Radioactive Tracers; Radioligand Assay; Radionuclide Imaging; Spleen; Vitamin B 12

In a pralatrexate phase I study, patients displayed a high incidence of mucositis of grades 3 and 4. Preliminary evaluations of the pharmacokinetics of the drug and its association with mucositis suggested that pralatrexate exposure (area under the concentration-time curve (AUC)) could be controlled with body size (e.g., weight or body surface area)-based dosing and that pretreatment with folic acid and vitamin B(12) might diminish the incidence and severity of mucositis. The study was amended, with revised dosing and vitamin B(12) administration. Data from 47 patients were evaluated using NONMEM. Weight and methylmalonic acid (MMA) level were predictive of pharmacokinetic (PK) variability. AUC and MMA level were positively correlated with the risk of developing mucositis. A lower AUC schedule with vitamin B(12) pretreatment may control mucositis without compromising efficacy. The covariates identified in this study are comparable with other antifolate analogs. The application of modeling was a critical step in the development of pralatrexate, yielding important suggestions for dose, scheduling, and pretreatment modifications.

Topics: Adult; Aged; Aminopterin; Antineoplastic Agents; Area Under Curve; Biomarkers; Body Size; Drug Administration Schedule; Female; Folic Acid Antagonists; Hodgkin Disease; Humans; Incidence; Lymphoma, Non-Hodgkin; Male; Methylmalonic Acid; Middle Aged; Models, Statistical; Mucositis; Predictive Value of Tests; Recurrence; Severity of Illness Index; Vitamin B 12

To compare tests for intestinal function with clinical scores after abdominal irradiation.. At the Department of Radiotherapy, Erfurt, Germany, intestinal changes were studied in 91 patients receiving abdominal radiotherapy between 1992 and 1996. Conventional fractionation (1.8-2 Gy per fraction, total doses 30.6-62.5 Gy) was applied. Before and at weekly intervals during radiotherapy, the clinical response was scored according to RTOG/EORTC for the upper and lower gastrointestinal (GI) tract. Resorption tests for vitamin B(12) and D-xylose were performed before the onset and immediately after treatment.. The clinical response displayed a well-defined dose-effect relationship with grade 1 effects in 5% and 50% of the patients at about 10 Gy and 50 Gy, respectively. For grade 2 reactions, 5%- and 50%-effective doses were 20-30 Gy and 60-80 Gy. Effects in the upper and lower GI tract were highly correlated. Changes in body weight did not show a correlation with other clinical symptoms. Changes in resorption also displayed a significant dose effect. However, no correlation was found with the clinical symptoms in the individual patient.. In the present study, the clinical manifestation of intestinal side effects according to RTOG/EORTC criteria was reflected by neither the vitamin B(12) nor by the D-xylose resorption test. Hence, these tests cannot be regarded as useful for objective quantitation of intestinal radiation injury.

Topics: Abdomen; Adolescent; Adult; Aged; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Female; Hodgkin Disease; Humans; Intestinal Absorption; Intestines; Kidney Neoplasms; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prospective Studies; Radiation Injuries; Radiotherapy; Radiotherapy Dosage; Rhabdomyosarcoma; Seminoma; Stomach Neoplasms; Testicular Neoplasms; Time Factors; Vitamin B 12; Xylose

Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors, however, appear to influence sEpo, and in this work, we performed studies to evaluate the role of the red blood cell precursor mass. We first compared the relationship of sEpo with Hb in patients with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin receptor (sTfR) levels < 3 mg/L (erythroid activity < 0.6 times normal), while the second one included 28 patients with beta-thalassemia intermedia having sTfR levels > 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with respect to Hb (8.3 +/- 1.6 v 8.0 +/- 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low erythroid activity (1,601 +/- 1,542 v 235 +/- 143 mU/mL, P < . 001). In fact, multivariate analysis of variance (ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001). Twenty patients undergoing allogeneic or autologous bone marrow transplantation (BMT) were then investigated. A marked increase in sEpo was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up to one log magnitude) were found before any change in Hb level. Similar observations were made in patients with megaloblastic anemia and in a case of pure red blood cell aplasia. These findings point to an inverse relationship between red blood cell precursor mass and sEpo: at any given Hb level, the higher the number of red blood cell precursors, the lower the sEpo concentration. The most likely explanation for this is that sEpo levels are regulated not only by the rate of renal production, but also by the rate of utilization by erythroid cells.

Topics: Anemia; Anemia, Aplastic; Anemia, Hypochromic; Anemia, Megaloblastic; Antineoplastic Combined Chemotherapy Protocols; beta-Thalassemia; Bone Marrow Transplantation; Erythrocyte Indices; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Feedback; Folic Acid; Hodgkin Disease; Humans; Iron; Kidney; Receptors, Transferrin; Transplantation Conditioning; Vitamin B 12

Serum cobalamin (vitamin B12) and unsaturated B12 binding capacity (UBBC) have been measured in 24 cases of hypereosinophilia: 16 were cases of hypereosinophilic syndrome (HES) and 8 of secondary eosinophilia. The two groups were similar with respect to absolute eosinophil counts. Serum cobalamin and UBBC were found to be markedly increased in most cases of HES and normal in secondary eosinophilia. This elevation of UBBC was mainly related to the increase of R binders (transcobalamins I and III). The elevated serum cobalamin and R binders in HES were due neither to a higher intracellular content of R binders nor to an increased release of these binders from eosinophils of HES. Pure fractions of eosinophils obtained from HES and secondary eosinophilia did not exhibit any difference in vitamin B12 binders. On the other hand, neutrophil-rich fractions from the same patients showed a higher content of intracellular B12 binding proteins than pure eosinophil fractions, irrespective of the cause of eosinophilia. These findings suggest that the increased serum vitamin B12 and UBBC could reflect an expanded pool of both eosinophils and neutrophils in HES and, thus, provide an additional argument for the inclusion of this syndrome in the group of myeloproliferative disorders.

Topics: Eosinophilia; Hodgkin Disease; Humans; Immunoblastic Lymphadenopathy; Leukocytes; Parasitic Diseases; Syndrome; Transcobalamins; Vitamin B 12

In 30 adult patients with III and IV Hodgkin's disease the studies of granulocytic turnover were performed. Bone marrow storage pool was measured by hydrocortisone test. Total blood granulocyte pool was judged by the estimation of muramidase activity and serum unsaturated vitamin B12 binding capacity. The epinephrine test was used for the marginated granulocyte pool determination. The circulating granulocyte pool was calculated from the count of granulocytes in the samples of venous blood. The tissue mobilization of granulocytes was measured by Senn's et al. method. After hydrocortisone application the releasing of the mature granulocytes from the bone-marrow was significantly lower in patients with Hodgkin's disease than in controls. The circulating and marginated pools of granulocytes in Hodgkin's disease did not differ from the normal persons. The tissue migration of granulocytes was decreased in patients with Hodgkin's disease. It is concluded that these abnormalities of granulocytic turnover in advanced Hodgkin's disease may be considered to be an additional cause of the defence mechanism in this disease.

Topics: Adult; Aged; Bone Marrow Examination; Epinephrine; Female; Granulocytes; Hodgkin Disease; Humans; Leukocyte Count; Male; Middle Aged; Muramidase; Vitamin B 12

Topics: Adrenal Gland Neoplasms; Adult; Binding Sites; Cells, Cultured; Centrifugation; Cobalt Radioisotopes; Dialysis; Female; Granulocytes; Hodgkin Disease; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lung Neoplasms; Male; Melanoma; Multiple Myeloma; Protein Binding; Proteinuria; Pyelonephritis; Time Factors; Vitamin B 12

Topics: Adult; Aged; Erythrocytes; Folic Acid; Histiocytes; Hodgkin Disease; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Vitamin B 12

Topics: Adult; Aged; Alpha-Globulins; Beta-Globulins; Blood Proteins; Child, Preschool; Chronic Disease; Female; Fever of Unknown Origin; Hodgkin Disease; Humans; Infections; Leukocyte Count; Leukocytosis; Liver Neoplasms; Lymphoma; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Protein Binding; Splenectomy; Vitamin B 12

Topics: Adult; Alkaline Phosphatase; Antibody Formation; Antigen-Antibody Reactions; Autopsy; Bone Marrow Examination; Cobalt Isotopes; Fluorescent Antibody Technique; Hodgkin Disease; Humans; Leukemia, Myeloid; Leukemia, Radiation-Induced; Male; Radiotherapy; Vitamin B 12

Topics: Adult; Anemia, Pernicious; Antibody Formation; Arthritis, Rheumatoid; Autoantibodies; Female; Fluorescent Antibody Technique; Folic Acid; Gastric Juice; Hemagglutination Tests; Hodgkin Disease; Humans; Immunodiffusion; Intrinsic Factor; Leukemia, Lymphoid; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Middle Aged; Multiple Myeloma; Pyrazoles; Radioimmunoassay; Vitamin B 12

Topics: Aged; Arteries; Calcium; Cobalt Isotopes; Colon; Colon, Sigmoid; Enterocolitis, Pseudomembranous; Feces; Female; Folic Acid; Hodgkin Disease; Humans; Intestine, Large; Intestine, Small; Iron; Lipids; Male; Middle Aged; Mucous Membrane; Radiography; Radioisotope Teletherapy; Rectal Diseases; Rectum; Serum Albumin; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms; Vitamin B 12; Xylose

Topics: Anemia, Hemolytic; Anemia, Pernicious; Hodgkin Disease; Humans; Leukemia; Lymphoma, Non-Hodgkin; Malabsorption Syndromes; Polycythemia Vera; Primary Myelofibrosis; Radioisotope Dilution Technique; Schilling Test; Vitamin B 12

Topics: Abdominal Neoplasms; Adolescent; Adult; Aged; Breast Neoplasms; Carcinoma; Child; Cobalt Isotopes; Female; Gastric Juice; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Hodgkin Disease; Humans; Intestinal Mucosa; Iodine Isotopes; Leiomyosarcoma; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Male; Mesothelioma; Methods; Middle Aged; Neuroblastoma; Pancreatic Neoplasms; Povidone; Radiation Effects; Radioisotope Teletherapy; Splenic Neoplasms; Time Factors; Triolein; Vitamin B 12

Topics: Adolescent; Child; Child, Preschool; Hodgkin Disease; Humans; Vitamin B 12

Topics: Blood; Folic Acid; Hodgkin Disease; Humans; In Vitro Techniques; Leukemia; Leukemia, Myeloid; Lymphoma; Lymphoma, Non-Hodgkin; Multiple Myeloma; Vitamin B 12

Topics: Bone Marrow; Bone Marrow Diseases; Hematologic Diseases; Hodgkin Disease; Humans; Leukemia; Myeloproliferative Disorders; Polycythemia Vera; Vitamin B 12

Topics: Corrinoids; Hematinics; Hodgkin Disease; Humans; Vitamin B 12