Effect of long-term treatment with recombinant human interleukin-3 in patients with myelodysplastic syndromes.
In a phase II study, involving nine patients with refractory anemia or refractory anemia with ring sideroblasts, the effects of treatment with recombinant human interleukin-3 (IL-3) on hematopoietic function were assessed. Doses of IL-3 ranging from 60 micrograms/m2 during weeks 1-6 to 125 micrograms/m2 during weeks 7-12 were administered as subcutaneous bolus injections three times per week for 12 weeks. Platelet counts increased in six patients. Platelet increase correlated with stable or decreased serum tumour necrosis factor alpha (TNF-alpha) levels, while an increase of TNF-alpha levels during IL-3 therapy occurred in patients with no change or a decrease of platelet counts. Leukocyte counts increased in two patients and reticulocytes in three, without an effect on hemoglobin levels. Morphological analysis of the bone marrow revealed an expansion of the myeloid compartment in seven of eight evaluable patients, mainly due to stimulation of the precursor cells. No improvement of the in vitro growth of hematopoietic progenitor cells was observed. Sequential cytogenetic analyses indicate that IL-3 treatment does not act preferentially on either the cytogenetically abnormal or the normal clones. These results suggest that long-term treatment with low-dose IL-3 stimulates megakaryopoiesis with increase of platelet counts, but that additional later-acting cytokines probably will be required to augment neutrophil and erythrocyte counts.
Ganser
A
A
Department of Hematology, University of Frankfurt, Germany.
Ottmann
O G
OG
Seipelt
G
G
Lindemann
A
A
Hess
U
U
Geissler
G
G
Maurer
A
A
Frisch
J
J
Schulz
G
G
Mertelsmann
R
R
D000368:Aged; D001772:Blood Cell Count; D001854:Bone Marrow Cells; D003582:Cytogenetics; D005260:Female; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D011994:Recombinant Proteins; D013997:Time Factors
D007377:Interleukin-3; D011994:Recombinant Proteins