Clinical use of recombinant human hematopoietic growth factors (GM-CSF, IL-3, EPO) in patients with myelodysplastic syndrome.
We have conducted several phase I/II clinical studies in a total of 65 MDS patients utilizing recombinant human hematopoietic growth factors including GM-CSF, IL-3, and EPO. Twenty-seven patients with MDS were treated with either continuous i.v. infusion or single daily s.c. injection of rhGM-CSF at dosages from 15 micrograms/m2 to 1000 micrograms/m2. All of them exhibited white cell responses during the treatment cycles, but no sustained rise in reticulocytes or platelets was recorded. In four of the patients, all with > or = 15% blast cells in the bone marrow, the percentage of circulating blast cells increased during treatment with rhGM-CSF (at dosages of 500 micrograms/m2 and 1000 micrograms/m2, respectively), although no leukemic conversion occurred. Of 9 patients treated so far with rhIL-3 at single daily s.c. dosages of 60 micrograms/m2, all exhibited white cell responses; 8 exhibited significant improved platelet and reticulocyte counts. Nineteen further patients received rhEPO for a period of 14 weeks by s.c. (10,000 U five times weekly) or i.v. bolus administration (150-450 U/kg). None of these patients experienced an increase in white cell and platelet counts. A significant increase of the reticulocyte count was recorded in 3 patients only. Another strategy involves the recruitment of leukemic cells into the cell cycle by hematopoietic growth factors followed by treatment with cycle-specific cytostatic agents. Therefore in 10 patients administration of rhGM-CSF (250 g/m2/day x 14, s.c.) was combined with Ara-C treatment (20 mg/m2/day x 14; s.c.). Initial results of this pilot study available in 5 patients indicated that this approach may control leukemic cell proliferation and may increase number of mature myeloid cells in both bone marrow and peripheral blood. A similar approach utilizing rhIL-3 in conjunction with Ara-C is on-going.
Herrmann
F
F
Department of Hematology and Oncology, University of Freiburg, Germany.
Mertelsmann
R
R
Lindemann
A
A
Ottmann
O G
OG
Seipelt
G
G
Oster
W
W
Hoelzer
D
D
Ganser
A
A
D001772:Blood Cell Count; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use; D004921:Erythropoietin / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000627:therapeutic use*; D006801:Humans; D007377:Interleukin-3 / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D003561:Cytarabine; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor