thioguanine-anhydrous and Anemia

Topics: Anemia; Ascites; Blood Coagulation Disorders; Bone Marrow; Busulfan; Chlorambucil; Humans; Hypertension, Portal; Primary Myelofibrosis; Prognosis; Spleen; Splenectomy; Thioguanine

Acute promyelocytic leukemia is characterized by bone marrow infiltration with hypergranular promyelocytes, often with Auer bodies. Clinically it is characterized by a hemorrhagic syndrome caused by a disseminated intravascular coagulation. Karyotypic studies have shown a frequent translocation t(15;17). Improved prognosis resulted from chemotherapy with DAT and treatment with heparin.

Topics: Acute Disease; Adolescent; Adult; Aged; Anemia; Antibiotics, Antineoplastic; Child; Child, Preschool; Cytarabine; Daunorubicin; Disseminated Intravascular Coagulation; Female; Heparin; Humans; Inclusion Bodies; Leukemia, Myeloid, Acute; Male; Middle Aged; Naphthacenes; Neoplastic Stem Cells; Thioguanine; Translocation, Genetic

To delineate the pathogenesis of the reduction in hemoglobin occurring in renal transplant patients treated with angiotensin converting enzyme inhibitors (ACEI) and azathioprine (AZA) a controlled, prospective trial of ACEI withdrawal was conducted. The ACEI was replaced by nifedipine or clonidine in 15 kidney transplant patients immunosuppressed with AZA and prednisone (enalapril in 14 and captopril in 1). Before and during 10 to 12 weeks after withdrawal of the ACEI, AZA metabolites, renal function parameters and hematological parameters including erythropoietin and reticulocytes were evaluated. Enalaprilat levels were measured and compared with 15 similar patients matched for transplant function and enalapril dosage immunosuppressed with cyclosporine and prednisone. AZA metabolites did not differ significantly in the presence or absence of the ACEI. Enalaprilat levels also showed no significant difference between the two patient groups treated with AZA or cyclosporine. Hematocrit and hemoglobin increased significantly from 37.5 +/- 6.4 to 39.7 +/- 3.6% (mean +/- SD, P = 0.02) and 12.8 +/- 2.2 to 13.5 +/- 1.2 g/dl, P = 0.04, respectively, 10 to 12 weeks after ACEI treatment had been discontinued. Simultaneously numbers of reticulocytes and erythropoietin concentrations rose significantly after 2, 4 and 10 weeks, with a peak at two weeks (from 14.1 +/- 3.8 to 20.6 +/- 8.0/1000, P < 0.05 and from 14.3 +/- 12.4 to 29.3 +/- 54.5 mU/ml, P < 0.05, respectively). In conclusion, ACEI-related anemia in renal transplant recipients seems to be due to the erythropoietin-lowering effect of this group of drugs. A pharmacokinetic interaction between AZA and enalapril is not likely since plasma enalaprilat levels were independent of the immunosuppressive regimen and AZA metabolite levels were unchanged in the presence and absence of the ACEI. Several mechanisms by which angiotensin converting enzyme blockade may cause a decrease in circulating erythropoietin are discussed.

Topics: Adult; Anemia; Angiotensin-Converting Enzyme Inhibitors; Azathioprine; Cyclosporine; Drug Interactions; Enalaprilat; Erythrocytes; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Prospective Studies; Thioguanine

The antimetabolite 6-thioguanine (6-TG) is utilized in the management of acute myelogenous leukemia (AML). Angiogenesis is a possible therapeutic target in hematologic tumors. Thus, we addressed the possibility that 6-TG may also act as an anti-angiogenic molecule. 6-TG inhibited endothelial cell proliferation triggered by fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor (VEGF) and delayed the repair of a mechanically wounded endothelial cell monolayer. Also, 6-TG inhibited sprouting within fibrin gel, morphogenesis on Matrigel, and collagen gel invasion by endothelial cells. 2-Aminopurine was ineffective. In vivo, 6-TG inhibited basal, VEGF-induced, and FGF2-induced vascularization in the chick embryo chorioallantoic membrane and prevented neovascularization triggered by leukemia LIK cells or their conditioned medium. Finally, bone marrow vascularization in AML patients was decreased to control values in the early remission phase and persisted unvaried after 8-12 months of maintenance therapy with 6-TG. Thus, 6-TG inhibits different steps of the angiogenesis process in vitro and exerts a potent anti-angiogenic activity in vivo. Its anti-angiogenic activity, together with its antimetabolite activity towards tumor cells, may contribute to its action during maintenance therapy in AML. These results suggest a new rationale for the use of purine analogs in the management of AML.

Topics: 2-Aminopurine; Acute Disease; Aged; Allantois; Anemia; Angiogenesis Inhibitors; Animals; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cattle; Cell Line, Transformed; Chick Embryo; Chorion; Cytarabine; Daunorubicin; Drug Evaluation; Endothelial Growth Factors; Endothelium, Vascular; Etoposide; Female; Fibroblast Growth Factor 2; Follow-Up Studies; Humans; Leukemia, Myeloid; Lymphokines; Male; Mice; Mice, Inbred BALB C; Middle Aged; Neovascularization, Pathologic; Neovascularization, Physiologic; Remission Induction; Stress, Mechanical; Thioguanine; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Topics: Aged; Anemia; Blood Cell Count; Bone Marrow Examination; Cytarabine; Diagnosis, Differential; Female; Humans; Leukemia, Myeloid, Acute; Primary Myelofibrosis; Thioguanine

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Aged; Anemia; Child; Cytarabine; DNA, Neoplasm; Female; Humans; Injections, Intravenous; Leukemia, Myeloid, Acute; Leukocytes; Male; Middle Aged; Muramidase; Nausea; Remission, Spontaneous; Sex Factors; Thioguanine; Thrombocytopenia; Time Factors; Vomiting

Topics: Aged; Alkaline Phosphatase; Anemia; Blood Transfusion; Bone Marrow; Busulfan; Cytarabine; Female; Histocytochemistry; Humans; Leukemia, Myeloid; Leukocytes; Male; Middle Aged; Pneumonia; Purpura; Radiography; Sepsis; Splenomegaly; Staphylococcal Infections; Tetracycline; Thioguanine

Topics: Acute Disease; Amino Sugars; Anemia; Antibiotics, Antineoplastic; Antineoplastic Agents; Blood Cell Count; Cyclophosphamide; Cytarabine; Glycosides; Humans; Injections, Intravenous; Injections, Subcutaneous; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukopenia; Lymphoma; Prednisone; Remission, Spontaneous; Thioguanine; Thrombocytopenia; Vincristine

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Alkylating Agents; Anemia; Anemia, Hemolytic, Autoimmune; Busulfan; Chlorambucil; Cyclophosphamide; Folic Acid Antagonists; Hemorrhage; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Neoplasms; Nitrogen Mustard Compounds; Phosphorus Isotopes; Splenectomy; Thioguanine; Triethylenemelamine

Topics: Anemia; Anemia, Hemolytic; Dermatitis, Atopic; Dermatitis, Contact; Eczema; Humans; Lupus Erythematosus, Systemic; Mercaptopurine; Scleroderma, Systemic; Thioguanine