Recombinant human GM-CSF enhances T cell-mediated cytotoxic function after ABMT for hematological malignancies.
The interactions of GM-CSF with cells of lymphoid lineage are not well understood and their clinical use has been focused on the acceleration of hematopoietic recovery. However, several reports have shown that human GM-CSF can affect certain T lymphocyte in vitro cytotoxic functions. To assess whether recombinant human GM-CSF (rhGM-CSF) has a more broadly based activity in the immune system, we studied its in vivo effects on endogenously-generated killer function in patients undergoing ABMT for hematologic malignancies. Eleven patients received rhGM-CSF after ABMT: eight received rhGM-CSF as a 2-h infusion daily from days +3 to +17 and three received rhGM-CSF until reaching > 500 x 10(6)/l granulocytes. Eight patients not enrolled in the rhGM-CSF therapy protocol served as controls. Natural killer (NK) cell activity and activated killer (AK) cell activity were studied before conditioning, during rhGM-CSF therapy and after withdrawal of GM-CSF. rhGM-CSF therapy does not affect NK activity. Circulating lymphocytes with the ability to kill AK-sensitive targets appear spontaneously in control ABMT patients. AK activity was 1.6 +/- 0.8% before ABMT increasing to 9 +/- 2.5% and 14 +/- 2.1% at 2 and 3 weeks after ABMT, respectively (p = 0.002). In rhGM-CSF-treated patients this phenomenon also occurs. AK activity increased from 2.4 +/- 1.5% before ABMT to 33.6 +/- 8.1% during rhGM-CSF administration (p = 0.001) and 17.5 +/- 3.4% after withdrawal (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Richard
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Department of Internal Medicine, Marqués de Valdecilla University Hospital, Faculty of Medicine, University of Cantabria, Santander, Spain.
Alsar
M J
MJ
Calavia
J
J
Bello-Fernandez
C
C
Baro
J
J
Loyola
I
I
Rios
R
R
Cuadrado
M A
MA
Gonzalez-Pardo
C
C
Iriondo
A
A
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000502:physiology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D007938:Leukemia / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged
D016178:Granulocyte-Macrophage Colony-Stimulating Factor