Sequential interleukin 3 and granulocyte-macrophage-colony stimulating factor therapy in patients with bone marrow failure with long-term follow-up of responses.
BACKGROUND
Interleukin-3 (IL-3) and granulocyte-macrophage-colony stimulating factor (GM-CSF) have synergistic, hematopoietic growth-promoting activity in preclinical studies. Because of the paucity of effective therapies for patients with chronic bone marrow failure states, the authors studied the biologic activity of sequential IL-3/GM-CSF in such patients.


METHODS
IL-3 was given subcutaneously for 5 days (at escalating doses of 0.15 microg/kg, 0.3 microg/kg, 0.6 microg/kg, 1.2 microg/kg, 2.5 microg/kg, 5.0 microg/kg, 10.0 microg/kg, or 15.0 microg/kg per day), and GM-CSF for was given subcutaneously for 9 days (at a dose of 5 microg/kg per day; Phase I 3 + 3 design) followed by 14 days of rest (total, 2 courses), then maintenance therapy.


RESULTS
The majority of 38 evaluable patients had aplastic anemia or myelodysplastic syndrome. Most patients (79%) had neutrophil responses. Ten patients (26%), all of whom were treated with IL-3 doses >/= 1.2 microg/kg per day, had platelet responses, with a median increase of 132 x 10(9)/L (range, 41-180 x 10(9)/L) over baseline in responders. Six patients (16%) had trilineage recovery, which could be durable (the longest ongoing at 6.5 years after therapy completion). The most common toxicities were low-grade fever, headache, and fatigue. The maximum tolerated doses were IL-3 at 10 microg/kg per day and GM-CSF at 5 microg/kg per day.


CONCLUSIONS
Sequential IL-3/GM-CSF effectively raised blood counts in some patients with bone marrow failure at doses that were tolerated well. These results indicate that early-acting growth factors can induce durable, multilineage responses in a subset of individuals with bone marrow failure.
Wu
Hillary H
HH
Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Talpaz
Moshe
M
Champlin
Richard E
RE
Pilat
Susan R
SR
Kurzrock
Razelle
R
D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000150:complications* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005221:Fatigue / Q000209:etiology; D005260:Female; D005334:Fever / Q000209:etiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006261:Headache / Q000209:etiology; D006801:Humans; D007279:Injections, Subcutaneous; D007377:Interleukin-3 / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000188:drug therapy*; D009503:Neutropenia / Q000188:drug therapy* / Q000209:etiology*; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000209:etiology*; D016896:Treatment Outcome
D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor