losartan-potassium and Leukemia--Myelomonocytic--Chronic

Most adult patients with hematopoietic failure due to myelodysplastic syndrome (MDS) are treated with supportive care measures, including hematopoietic growth factors (epoetin alfa, darbepoetin alfa, filgrastim, pegfilgrastim, sargramostim), red blood cell or platelet transfusions, and antimicrobial agents. Allogeneic stem cell transplantation can be curative, but only a small subset of patients are eligible for transplantation, and until recently there were few options other than supportive care for transplant-ineligible patients. Since 2004, the US Food and Drug Administration (FDA) has approved three new therapies specifically for the indication of MDS: two DNA methyltransferase inhibitors (azacitidine and decitabine) and an immunomodulatory agent (lenalidomide). Several other drugs are used by clinicians for treatment of patients with MDS, but are not specifically FDA-approved for this indication. With several therapeutic options available, yet none of them effective in the majority of cases, it can be challenging for clinicians to choose the most appropriate treatment for an individual patient. Here we discuss a risk-based management approach to MDS that incorporates recent data regarding these new therapies. While many questions remain about the optimal use of newer agents, the long-standing perception of MDS as a syndrome where therapeutic nihilism is the only realistic approach is slowly beginning to change.

Topics: Anemia, Sideroblastic; Antilymphocyte Serum; Azacitidine; Benzoates; Decitabine; Deferasirox; DNA Modification Methylases; Enzyme Inhibitors; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Histone Deacetylase Inhibitors; Humans; Immunosuppressive Agents; Interleukin-11; Iron Chelating Agents; Lenalidomide; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Prognosis; Risk; Stem Cell Transplantation; Thalidomide; Triazoles

Topics: Aged; Aneuploidy; Antimetabolites, Antineoplastic; Azacitidine; Chromosomes, Human, Pair 21; Erythropoietin; Fatal Outcome; Granulocyte Colony-Stimulating Factor; GTP Phosphohydrolases; Humans; Karyotyping; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Male; Membrane Proteins; Neoplasms, Second Primary

Recombinant human erythropoietin (rHuEpo) improves anemia in 25% of patients with myelodysplastic syndromes (MDS). The variable and sometimes low response rate to rHuEpo treatment raises the question whether the existence of autoantibodies against erythropoietin (epo) is partially responsible. In the present study we investigated the presence of anti-epo autoantibodies in MDS patients.. Forty-three patients with MDS were studied. Sixteen patients had refractory anemia (RA), 13 had RA with ringed sideroblasts, 3 had RA with excess of blasts (RAEB), 9 had RAEB in transformation and 2 patients had chronic myelomonocytic leukemia. They were divided in 3 groups according to rHuEpo treatment. Group A consisted of 10 patients who did not receive rHuEpo treatment. Group B included 13 patients who were on rHuEpo treatment (150 IU/kg subcutaneously, 3 times weekly) showing an increase of hemoglobin (Hb) values or reduction of transfusion requirements and Group C consisted of 20 patients who did not respond or stopped responding to rHuEpo treatment. Laboratory studies consisted of a complete blood cell count, measurement of serum epo and determination of anti-epo antibodies using ELISA.. There were no significant differences with regard to age and sex among the three groups. No autoantibodies against epo were found in the examined sera, apart from a female patient from group A who showed a low positive titer.. We suggest that anti-epo autoantibodies do not contribute to the development of MDS-related anemia and are not responsible for the modest response to rHuEpo treatment. Further investigation is needed to identify possible reasons for the low response rate to rHuEpo treatment.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Antibody Specificity; Autoantibodies; Autoantigens; Blood Cell Count; Blood Transfusion; Combined Modality Therapy; Erythropoietin; Female; Hemoglobins; Humans; Isoantibodies; Isoantigens; Leukemia, Myelomonocytic, Chronic; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins; Treatment Failure

Topics: Aged; Anemia; Bone Marrow; Erythropoietin; Humans; Kidney Failure, Chronic; Leukemia, Myelomonocytic, Chronic; Male; Recombinant Proteins

Topics: Aged; Anemia; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Hepatomegaly; Humans; Leukemia, Myelomonocytic, Chronic; Male

Topics: Aged; Blast Crisis; Erythropoietin; Female; Hemoglobins; Humans; Leukemia, Myelomonocytic, Chronic; Male; Middle Aged; Recombinant Proteins; Reticulocytes

Four-stem-cell assays, which evaluate megakaryocytic (CFU-Meg), immature and mature erythropoietic (BFU-E, CFU-E), and granulocyte-macrophage (CFU-GM) colony formation, were performed in nine patients with myelodysplastic syndromes (MDS). The CFU-Meg, BFU-E, and CFU-E colony growths were disturbed more often than the CFU-GM colony formation. A CFU-E increase was not recognized in most MDS patients, but a dose-dependent increase of bone marrow CFU-Es in response to erythropoietin (EPO) was recognized only in two refractory anemia (RA) patients whose CFU-Es were more than one tenth of normal controls. One patient with RA and the other with chronic myelomonocytic leukemia (CMML), both of whose bone marrow CFU-Es did not increase at the higher dose of EPO in vitro, were treated with recombinant human EPO (rHuEPO), resulting in no effects. The responsiveness of patients with MDS to various recombinant hemopoietic factors might be predicted by both the residual degree of bone marrow hematopoietic precursor cells and the response of stem cells to the higher doses of each hemopoietic factor.

Topics: Adult; Aged; Anemia; Bone Marrow; Colony-Forming Units Assay; Erythropoietin; Female; Hematopoietic Stem Cells; Humans; Leukemia, Myelomonocytic, Chronic; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins