Increased numbers of circulating haematopoietic progenitor cells after treatment with high-dose interleukin-2 in cancer patients.
Immunotherapy with recombinant interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has been applied to patients with metastatic cancers for its antitumour activity. In the present study we investigated the effects of in vivo administration of IL-2 (3 x 10(6) U/m2/d, continuously i.v.) on haematopoiesis. Six patients with disseminated renal cell carcinoma, treated with IL-2 and LAK cells, were monitored for the numbers of white blood cells and circulating haematopoietic progenitor cells (HPC). During IL-2 treatment lymphopenia developed, followed by lymphocytosis after discontinuation of IL-2 infusions. IL-2 administration also resulted in neutrophilia and eosinophilia. Absolute numbers of circulating HPC declined markedly during IL-2 treatment. However, after completing IL-2 infusions, the numbers of circulating erythroid (BFU-E), myeloid (CFU-GM) and multipotential progenitor cells (CFU-GEMM) strongly increased, reaching a maximum after 5 d (day 10 from the start of IL-2 treatment). This increase did not result from repeated leucaphereses, since patients treated with IL-2 alone showed a similar response. In comparison with pretreatment levels the pool of circulating HPC expanded about 20-fold. This study illustrates that IL-2 treatment has a biphasic effect on the frequency of circulating BFU-E, CFU-GM and CFU-GEMM, causing a decrease during IL-2 infusion, followed by an increase after IL-2 administration. The total number of progenitor cells harvested by four consecutive leucaphereses is in the range that is commonly used for peripheral blood stem cell autografting.
Schaafsma
M R
MR
Department of Haematology, University Medical Centre, Leiden, The Netherlands.
Fibbe
W E
WE
van der Harst
D
D
Duinkerken
N
N
Brand
A
A
Osanto
S
S
Franks
C R
CR
Willemze
R
R
Falkenburg
J H
JH
D002292:Carcinoma, Renal Cell / Q000097:blood / Q000628:therapy*; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000628:therapy*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007937:Leukapheresis; D007958:Leukocyte Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use
D007376:Interleukin-2; D011994:Recombinant Proteins