Natural killer cell activity in chronic lymphocytic leukemia patients treated with fludarabine

Cancer Chemotherapy and Pharmacology
L E RobertsonJ A Nelson

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 pati...Continue Reading

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Citations

Sep 11, 2008·Cancer Chemotherapy and Pharmacology·Erica L WoodahlJeannine S McCune
Jul 27, 2001·British Journal of Haematology·M W LowdellH G Prentice
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May 20, 2015·Cancer Chemotherapy and Pharmacology·Jeannine S McCuneShelly Heimfeld
Sep 23, 2008·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Christopher C DvorakMorton J Cowan
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Jun 14, 2020·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Cristina F ContrerasChristopher C Dvorak

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