TREATMENT OF THE ANEMIA OF APLASTIC-ANEMIA PATIENTS WITH RECOMBINANT-HUMAN-ERYTHROPOIETIN IN COMBINATION WITH GRANULOCYTE-COLONY-STIMULATING FACTOR - A MULTICENTER RANDOMIZED CONTROLLED-STUDY
M. Bessho et al., TREATMENT OF THE ANEMIA OF APLASTIC-ANEMIA PATIENTS WITH RECOMBINANT-HUMAN-ERYTHROPOIETIN IN COMBINATION WITH GRANULOCYTE-COLONY-STIMULATING FACTOR - A MULTICENTER RANDOMIZED CONTROLLED-STUDY, European journal of haematology, 58(4), 1997, pp. 265-272
A multicenter randomized controlled study was undertaken in order to d
etermine whether epoetin beta (EPO) ameliorates the anemia in aplastic
anemia (AA) patients treated with granulocyte colony-stimulating fact
or (G-CSF). Enrolled patients were randomized into 3 groups: group C r
eceiving G-CSF alone as the control; group L receiving G-CSF and 200 I
U/kg of EPO; group H receiving G-CSF and 400 IU/kg of EPO. Throughout
the study, the dose and the administration interval of G-CSF were adju
sted to maintain neutrophil counts between 1000 and 5000 mu l. EPO was
administered subcutaneously for 12 wk as the first step in treatment
and when favorable effects were observed over this period, treatment w
as continued for another 12 wk as the second step in treatment. Signif
icant erythroid responses were defined as increases in untransfused he
moglobin values >1.0 g/dl or >50% decreases in RBC transfusion require
ments over the treatment period. Of 131 patients enrolled, 88 patients
allocated to groups L and H were evaluated for toxicity to EPO and 11
0 were evaluated for erythroid responses. Four of the 31 patients (12.
9%) in group C, 6 of the 41 patients (14.6%) of group L, and 14 of the
38 patients (36.8%) of group H showed erythroid responses in the firs
t step in treatment. The erythroid responses of group H were significa
ntly higher than those of the other 2 groups (p<0.05). The significant
effects of EPO were due to erythroid responses in non-severe AA. Resp
onding patients were significantly different from non-responders with
regard to disease severity, hemoglobin concentration, reticulocyte cou
nt, serum endogenous erythropoietin levels and serum transferrin recep
tors; non-severe AA patients were more likely to respond to EPO, and r
esponding patients had lower serum EPO and higher hemoglobin concentra
tion, reticulocyte count and serum transferrin receptors than non-resp
onders. The response rate increased in the second step in treatment, s
uggesting that long-term treatment improved the efficacy of EPO. No se
rious side-effects were observed. From these results, we conclude that
EPO given in combination with G-CSF is a safe and effective alternati
ve for the treatment of anemia of a subset of AA patients.