In vivo effects of sequential granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-2 (IL-2) on depressed peripheral blood dendritic cell (DC) counts in patients with stage IIB–IV melanoma

Abstract

Abstract Introduction: While leukocytosis is common during GM-CSF therapy for melanoma, it is unknown whether this translates to increases in circulating DC. Theoretical anti-tumor mechanisms of action of sequential GM-CSF/IL-2 might include a cumulative gain in peripheral DC counts. Methods: Ten patients with Stage IIB–IV melanoma were treated with GM-CSF 125 mμg/m 2 for 14 days, IL-2, 9 million IU/m2 for 4 days followed by a 10 day rest. Assays of the peripheral blood were performed at baseline, the start of each cycle and after the completion of 6 cycles. Counts were compared to those of 29 normal volunteers (NL), 30 patients without evidence of disease (NED), and 14 patients with documented tumor burden (TB). Results: Normal DC counts were determined to be 25 ± 6 (per mcL). Melanoma patients with TB had DC counts of 18 ± 9. While DC counts were statistically different between NL and TB patients (p 3 per mμL) after cycle 4 (p Conclusions: While there was a significant increase in WBC after two cycles of GM-CSF/IL-2, no detectable cumulative effect on DC counts could be demonstrated. Table . DC Counts in Melanoma Patients Receiving Biotherapy Cycle 1 (pre) n = 10 Cycle 2 n = 9 Cycle 3 n = 10 Cycle 4 n = 10 Cycle 5 n = 10 Cycle 6 n = 10 Post n = 10 WBC (× 10 3 /μL) 6.4 (1.3) 7.3 (1.3) 8.6 (1.6) 8.9 (1.6) 8.9 (2.0) 9.0 (1.0) 8.2 (1.6) # DC /μL 18 (8) 14 (7) 16 (5) 17 (6) 17 (5) 18 (4) 19 (6) # Lymphs (× 10 3 /μL) 1.9 (0.3) 2.5 (0.6) 2.8 (0.7) 3.1 (0.7) 3.3 (0.7) 3.5 (0.7) 3.2 (1.0) # Eosinos (× 10 3 /μL) 0.2 (0.3) 0.7 (0.5) 1.2 (0.5) 1.0 (0.8) 1.0 (0.9) 1.0 (0.4) 0.9 (0.5)