High-dose
cytosine arabinoside (HiDAC) and intermediate-dose
cytosine arabinoside (IDAC) have been introduced as effective and safe
consolidation chemotherapy in
acute myeloid leukemia, with relatively low rates of life-threatening
infections despite the high total dose of the
cytostatic drug. To explore the biological background of low toxicity, we examined the numbers, immunophenotype, and functional properties of granulocytes in patients with
acute myeloid leukemia receiving HiDAC or IDAC. Interestingly, the absolute numbers of neutrophils remained >500/microl until day 10 in 92 of 125 (74%) HiDAC cycles and in 106 of 113 (94%) IDAC cycles. As assessed by electron microscopy, these day-10 granulocytes surviving
chemotherapy were found to be mature cells containing secondary granules and phagolysosomes. They also expressed opsonization- and phagocytosis-linked surface Ags (C3biR, CR1, C1qR, C5aR, FcgammaRI, FcgammaRII, FcgammaRIII, and
G-CSF and
GM-CSF receptors) like neutrophils in healthy controls. Moreover, these day-10 neutrophils exhibited oxidative burst activity and took up and digested bacteria in the same way as neutrophils in healthy controls. There was a negative correlation between absolute neutrophil counts and severe
infections in HiDAC- and IDAC-treated patients with a later onset of
infections in IDAC patients (median: IDAC, day 18; HiDAC, day 16). Together, functionally mature neutrophils are detectable at least until day 10 in patients treated with HiDAC or IDAC, and may explain the relatively low hematologic toxicity of these consolidation protocols. IDAC is a superior protocol in this regard and may therefore be most suitable for elderly patients and those at high risk for severe
infections.