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Activation of lymphocytes induced by recombinant human granulocyte-
macrophage colony-stimulating factor in patients with malignant lymphoma
AD Ho, R Haas, G Wulf, W Knauf, R Ehrhardt, B Heilig, M Korbling, G Schulz and W Hunstein
Department of Internal Medicine V and Poliklinik, University of Heidelberg,
FRG.
To investigate effects of recombinant human granulocyte-macrophage
colony-stimulating factor (rhGM-CSF) on lymphoid cells in vivo, we
monitored changes in absolute lymphocyte counts, plasma concentrations of
soluble interleukin-2 receptor (sIL-2R) and soluble cytotoxic/suppressor
(sCD8) antigens, and phenotypic changes of surface membrane antigens of
peripheral mononuclear cells from 14 patients with malignant lymphoma
treated with rhGM-CSF. Eight of the 14 patients had relapsed or had
refractory non-Hodgkin's lymphoma (NHL) and received rhGM-CSF after
intensive chemotherapy with novantrone (NO) and high- dose Ara-C (AC)
(NOAC) as salvage regimen. Six other patients with NHL or Hodgkin's disease
(HD) were in complete remission and treated with rhGM-CSF to enhance
peripheral hematopoietic progenitor cell harvest for autografting. An
increase in absolute lymphocyte count at the zenith of leukocyte elevation
and a drastic increase in concentration of sIL-2R from a median of 565 U/mL
to 6,700 U/mL on rhGM-CSF infusion were found in all patients. There was
also a moderate increase in sCD8 levels from a median of 277 U/mL to 470
U/mL. Ten patients were available for serial studies of phenotypic changes
in surface membrane antigens. A significant increase in CD25+ (IL-2R+) (P =
.0020) and CD4+ (P = .0137) lymphocytes was observed in all patients, but
no significant change in CD3+, CD8+, TCR delta 1+, or CD19+ cells.
Elevations in absolute lymphocyte counts or in concentrations of sIL-2R or
sCD8 were not observed in four other patients during recovery from
intensive chemotherapy without rhGM-CSF support. Our results provide
evidence that administration of rhGM-CSF might activate lymphocytes in
vivo. The impact of this activation on the remission rate and duration, as
well as survival in patients with NHL, warrants further investigation.
Volume 75,
Issue 1,
pp. 203-212,
01/01/1990
Copyright © 1990 by The American Society of Hematology
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