Therapeutic effect of heme arginate in myelodysplastic syndromes.
In order to investigate, whether heme would induce a response in myelodysplastic syndromes (MDS), 14 symptomatic patients (4 RA, 3 RARS and 7 RAEB) were treated with infusions of heme arginate 3 mg/kg body weight on 4 consecutive days, mostly for six cycles at 2-week intervals. Three of 14 patients (21%) showed an improvement in anemia (97-152, 79-120 and 92-114 g/l) within a few weeks, and 1 showed a milder increase in hemoglobin level (102-118 g/l). Of the 2 responders with marked thrombocytopenia, 1 showed an improvement in the platelet count (7-37 x 10(9)/l) and her regular need for red cell and platelet transfusions ceased. Some regression in bone marrow (BM) cytology was seen in all 3 responders. One of the responders is still in remission 41 months after cessation of the treatment, while in the other 2 the response lasted for 26 and 5 months. Four patients progressed during the treatment: 1 RA to RAEB, 1 RAEB to RAEBt and 2 RAEB, both with very complex chromosomal abnormalities at the beginning of the therapy, to acute erythroleukemia (AML-M6). Pretreatment delta-aminolevulinic acid synthase and heme synthase activities were generally low. Five patients had mild thrombophlebitis, but not after the infusion procedure was changed. No other side-effects common to growth factors occurred. In conclusion, it is likely that heme arginate has a therapeutic effect on some MDS patients, obviously by stimulating erythropoiesis. The response may be long-lasting.
Timonen
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Department of Internal Medicine, University of Oulu, Finland.
Kauma
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D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001120:Arginine / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001853:Bone Marrow / Q000473:pathology; D003404:Creatinine / Q000097:blood; D004921:Erythropoietin / Q000097:blood; D005260:Female; D006418:Heme / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
D004921:Erythropoietin; D006418:Heme; D001120:Arginine; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C048849:heme arginate