Prospective, randomized trial of sequential interleukin-3 and granulocyte- or granulocyte-macrophage colony-stimulating factor after standard-dose chemotherapy in cancer patients

Sergio Palmeri, Vita Leonardi, Marco Danova, Camillo Porta, Silvia Ferrari, Gianluca Fincato, Pietro Citarrella

Research output: Contribution to journalArticle

Abstract

Background and Objectives. Several in vitro and animal studies have shown that IL-3 primes hematopoietic stem cells to become more sensitive to later acting growth factor. We wanted to compare the toxicity and the synergistic stimulatory effect of interleukin-3 (IL-3) followed by granulocyte colonystimulating factor (G-CFS) or granulocyte-macrophage colony-stimulating factor (GM-CSF) on white blood cell (WBC) and platelet counts, after standarddose chemotherapy (CT) in patients with solid tumors. Design and Methods. Fifty consecutive cancer patients with thrombocytopenia and/or leukopenia registered during a previous course of CT were randomized to receive, after the following course, IL-3 (10 μg/kg/day, s.c., day 1-5) followed by G- or GMCSF (5 μg/kg/day, day 6-8). Results. The nadir of WBC in the cycles supported with the combination of IL-3 and G-CSF was significantly higher than that observed in the CT cycles not supported by growth factors (p <0.005). Furthermore, severe leukopenia was abrogated in all the cycles supported with IL-3+G-CSF, while in the cycles without cytokines, this event was registered in 62.5% of the cases (p<0.0005). Finally, the recovery of WBC was achieved a mean of 4 days earlier in the cycles supported with IL- 3+G-CSF. As for thrombocytoprotection, no significant differences were evidenced, but severe thrombocytopenia was abrogated in all the cycles supported by IL-3+G-CSF (p <0.05). Furthermore, platelet recovery after CT was achieved on average 3.5 days earlier in the IL-3+G-CSF group than in the previous cycles. The nadir of WBC count in the cycles supported by the combination of IL-3 and GMCSF was significantly higher than that observed in the CT cycles not supported by growth factors (p <0.005). Furthermore, severe leukopenia was abrogated in 40% of the cycles supported by IL-3+GMCSF, while in the cycles without cytokines, this event was registered in 80% of the cases (p <0.005). Finally, the recovery of WBC was achieved a mean of 3.5 days earlier in the cycles supported by IL-3+GM-CSF. As far as thrombocytoprotection is concerned, there were no significant differences in the nadir between the cycles supported by the association IL-3+GM-CSF and the cycles not supported by cytokines. However, severe thrombocytopenia was registered in 20% of the cycles not supported by growth factors but in only 10% of the cycles supported by IL-3+GM-CSF (p <0.05). Furthermore, platelet recovery after CT was achieved on average 3 days earlier in the IL-3+GMCSF group. The combination of IL-3 and G-CSF would appear to be more effective than the combination of IL-3 and GM-CSF In the control of both severe thrombocytopenia and leukopenia. Indeed, severe leukopenia was abrogated in all the cycles in arm A, but only in 40% of the cycles in arm B (p <0.0005). Furthermore, considering a platelet count below 49 x 109/L, such a toxicity was avoided in 90% of the cycles In arm B, but in 100% of the cycles in arm A (p <0.05). Interpretation and Conclusions. The sequential administration of IL-3 and myeloid growth factors can be given safely after standard-dose CT programs. The combination of IL-3 + G-CSF seems to be more effective than the association IL-3 + GM-CSF in the control of CT-induced myelosuppression, even though further studies are needed to confirm these results.

Original languageEnglish
Pages (from-to)1016-1023
Number of pages8
JournalHaematologica
Volume84
Issue number11
Publication statusPublished - Nov 1999

Keywords

  • Chemotherapyinduced myelosuppression
  • G-CSF
  • GM-CSF
  • Interleukin-3

ASJC Scopus subject areas

  • Hematology

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