cholecalciferol and Preleukemia

The myelodysplastic syndromes represent a preleukaemic state in which a clonal abnormality of haemopoietic stem cell is characterised by a variety of phenotypic manifestations with varying degrees of ineffective haemopoiesis. This state probably develops as a sequence of events in which the earliest stages may be difficult to detect by conventional pathological techniques. The process is characterised by genetic changes leading to abnormal control of cell proliferation and differentiation. Expansion of an abnormal clone may be related to independence from normal growth factors, insensitivity to normal inhibitory factors, suppression of normal clonal growth, or changes in the immunological or nutritional condition of the host. The haematological picture is of peripheral blood cytopenias: a cellular bone marrow, and functional abnormalities of erythroid, myeloid, and megakaryocytic cells. In most cases marrow cells have an abnormal DNA content, often with disturbances of the cell cycle: an abnormal karyotype is common in premalignant clones. Growth abnormalities of erythroid or granulocyte-macrophage progenitors are common in marrow cultures, and lineage specific surface membrane markers indicate aberrations of differentiation. Progression of the disorder may occur through clonal expansion or through clonal evolution with a greater degree of malignancy. Current attempts to influence abnormal growth and differentiation have had only limited success. Clinical recognition of the syndrome depends on an acute awareness of the signs combined with the identification of clonal and functional abnormalities.

Topics: Anemia, Refractory, with Excess of Blasts; Animals; Antineoplastic Agents; Blood Cell Count; Bone Marrow; Cell Transformation, Neoplastic; Cholecalciferol; Chromosome Aberrations; Chromosome Disorders; Colony-Forming Units Assay; Colony-Stimulating Factors; DNA; Hematopoietic Stem Cells; Humans; Leukemia; Leukemia, Radiation-Induced; Mice; Myelodysplastic Syndromes; Oncogenes; Preleukemia; Rats; Tretinoin

We have examined the efficacy of various drugs in 44 patients with MDS and found the different effectiveness which depends on the type of MDS. Namely, RA appears to respond to steroid hormone, androgen, and/or vitamin D3, regardless of single or combined use. In particular, it is obvious in androgen, and as our previous reports, high content of acidic ferritin in RBC with RA have changed to more basic ones by treatment with androgen. On the contrary, these drugs were not effective on RAEB, RAEB-T, and CMML. A long-term observation is needed to determine whether the prolonged or decreased occurrence of leukemia could be obtained in the effective cases with RA. Most of the cases who did not develop overt leukemia during this study died of bleeding or infections due to thrombocytopenia or leukocytopenia, thus indicating that supportive therapies are important in patients with MDS. Since it has recently been reported that recombinant G-CSF or GM-CSF is helpful to increase the number of leucocyte and to enhance their functional recovery in MDS, these factors may be powerful agents against infections when they are carefully used with regard to the activation of leukemic clones.

Topics: Adult; Aged; Androgens; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Blast Crisis; Cholecalciferol; Chromosome Aberrations; Cytarabine; Female; Humans; Leukemia, Myeloid; Male; Middle Aged; Preleukemia; Prognosis