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

• Published in: Journal of the American College of Surgeons Vol. 199; no. 3; p. 81
• Main Authors: Zapas, John L., Hasskamp, Joanne, Beam, Sandra, Brown, Sally, Elias, E.George
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-09-2004
• ISSN: 1072-7515; 1879-1190
• DOI: 10.1016/j.jamcollsurg.2004.05.177

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 < 0.01), there were no differences between NL and NED 24 ± 7. Patients receiving GM-CSF/IL-2 had DC counts similar to TB, 18 ± 8. There was a significant cumulative increase in WBC from the baseline value of 6.4 to a maximum value of 9.0(× 10
3 per mμL) after cycle 4 (p < 0.01). While the WBC remained high after cycle 6 (8.2), there was no significant elevation in DC counts during therapy. WBC fractions showing a significant gain in numbers were lymphocytes and eosinophils after Cycle 2.
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)