Therapy with recombinant human erythropoietin in patients with myelodysplastic syndromes.
We conducted a Phase I-II trial of recombinant human erythropoietin-beta (rhEPO) in patients with myelodysplastic syndrome (MDS). Patients with anemia and pathologically confirmed MDS were eligible for the study. Treatment consisted of rhEPO by subcutaneous injection thrice weekly for 6 weeks at one of three dose levels (100 U/kg (three patients), 200 U/kg (three patients) and 400 U/kg (14 patients)). Ferrous sulfate (325 mg po tid) was also administered if the transferrin saturation was below 30% (two patients). Patients were monitored with weekly CBC, white cell differential, and reticulocyte counts. Bone marrow examinations were performed at the conclusion of the treatment period and after a 2 week washout period. Patients who responded to therapy were continued on rhEPO at the same dose for 6 additional months. Response criteria included: 50% reduction in transfusion requirements compared with the 6 week pre-study period; doubling of reticulocyte count that was maintained on two determinations at least 1 week apart; or an increase in hemoglobin by at least 1.2 gm/dl without transfusions. Pre-treatment factors potentially predictive of response were analyzed by univariate analysis and in a multivariate fashion by classification and regression trees. Seven of the twenty patients sustained an untransfused rise in serum hemoglobin > or = 1.2 gm/dl. Four of the sixteen patients (including three of seven patients experiencing a rise in serum hemoglobin) who were transfusion-dependent prior to the study achieved a reduction or elimination of their transfusion requirements. Five of thirteen patients who received rhEPO during the extension phase had a continued response. A low baseline erythropoietin level (< 50 mU/ml) was the best predictor of hemoglobin response when controlling for other variables. rhEPO has a role in the treatment of certain patients with MDS, particularly in those whose endogenous serum erythropoietin levels are not markedly elevated.
Stone
R M
RM
Department of Medicine, Dana-Farber Cancer Institute, Boston, MA 02115.
Bernstein
S H
SH
Demetri
G
G
Facklam
D P
DP
Arthur
K
K
Andersen
J
J
Aster
J C
JC
Kufe
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D011994:Recombinant Proteins; D004921:Erythropoietin