Treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. A phase I-II trial.
OBJECTIVE
To determine the hematopoietic effects and toxicity of recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with myelodysplastic syndromes.


METHODS
The G-CSF was administered by daily subcutaneous injection to outpatients in a phase I-II trial. Dose was escalated every 2 weeks between 0.1 to 3.0 micrograms/kg body weight.d over an 8-week treatment period.


METHODS
Outpatient clinical research center at a university hospital.


METHODS
Twelve consecutive patients with myelodysplastic syndromes: two refractory anemia, seven refractory anemia with excess of blasts, three refractory anemia with excess of blasts in transformation.


RESULTS
In 10 of 12 patients, elevations in blood leukocyte counts (2- to 10-fold) and absolute neutrophil counts (5- to 40-fold) were seen over the 8-week treatment period. Five of seven severely neutropenic patients (absolute neutrophil count, less than 0.5 x 10(9)/L) had a rise in count to 1.2 to 16.3 x 10(9)/L. Increased reticulocyte counts occurred in 5 patients, and were associated with decreased transfusion requirements in 2 of 9 erythrocyte transfusion-dependent patients. Treatment with G-CSF enhanced marrow myeloid cell maturation in 9 of 11 evaluable patients. Neutrophil chemotaxis and phagocytosis in vitro were improved or unchanged after treatment in 6 of 8 patients tested. In 11 of 12 patients, there were no substantial changes in platelet, lymphocyte, eosinophil, or monocyte counts. Three responding patients initially had abnormal cytogenetics that persisted after G-CSF therapy, suggesting induced differentiation of the abnormal clone. The therapy was associated with minimal toxicity. None of the patients' conditions converted to acute leukemia during treatment or in short-term follow-up.


CONCLUSIONS
Treatment with G-CSF administered by subcutaneous injection is well tolerated and effective for improving the neutropenia, and less commonly the transfusion-dependent anemia, over 6 to 8 weeks in patients with myelodysplastic syndromes.
Negrin
R S
RS
Stanford University Medical Center, California.
Haeuber
D H
DH
Nagler
A
A
Olds
L C
LC
Donlon
T
T
Souza
L M
LM
Greenberg
P L
PL
D000368:Aged; D000753:Anemia, Refractory / Q000628:therapy; D000754:Anemia, Refractory, with Excess of Blasts / Q000628:therapy; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000009:adverse effects / Q000627:therapeutic use*; D004341:Drug Evaluation; D004906:Erythrocyte Count / Q000187:drug effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012156:Reticulocytes / Q000187:drug effects
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor