Sequential interleukin 3 and granulocyte-macrophage–colony stimulating factor therapy in patients with bone marrow failure with long-term follow-up of responses

✍ Scribed by Hillary H. Wu; Moshe Talpaz; Richard E. Champlin; Susan R. Pilat; Razelle Kurzrock

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 138 KB
• Volume: 98
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/cncr.11810

✦ Synopsis

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.