Natural killer cell activity in chronic lymphocytic leukemia patients treated with fludarabine.
Cancer Chemother Pharmacol
; 37(5): 445-50, 1996.
Article
em En
| MEDLINE
| ID: mdl-8599867
ABSTRACT
Fludarabine, the 5'-monophosphate of 9-beta-D-arabinofuranosyl-2- fluoroadenine (FaraAMP), is effective in the treatment of chronic lymphocytic leukemia (CLL) and has been demonstrated to increase natural killer (NK) cell lytic activity (NKa) in humans and mice. To determine the effect of FaraAMP on NK cells in CLL, we analyzed NKa toward K562 targets after in vitro incubation with FaraAMP and after in vivo exposure to fludarabine. Pretreatment analysis of peripheral blood from 12 CLL patients (9 untreated) revealed median number of NK cells 500/microliter (range 290-1160); median NKa lytic unit30/10(6) cells (range 5-80). These results were similar to those from healthy adult donors. After exposure to 3, 30 or 300 microM FaraAMP, the median maximum stimulation index (NKa FaraAMP/NKa) was 1.2 (range 0.9-1.5), within the range observed in normal adults. FaraA also stimulated NKa in vitro toward autologous CLL cells in two of five patients as measured by a dye-exclusion assay. In three patients following three or more treatment courses of fludarabine (30 mg/m2 per day for 5 days) the NK cell number and NKa were maintained near pretreatment values. Phenotypic analysis of the peripheral mononuclear cells in 34 consecutive CLL patients revealed a marked reduction in CD5/CD20 and CD4 cell numbers after three courses of fludarabine with less effect on CD8 and CD56 cells. These results indicate that fludarabine spares NK cells and may stimulate NKa in some CLL patients.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vidarabina
/
Células Matadoras Naturais
/
Leucemia Linfocítica Crônica de Células B
/
Antineoplásicos
Limite:
Adult
/
Humans
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos