Altered oxidative product formation in neutrophils of patients recovering
from therapy for acute leukemia
BL Powell, P Olbrantz, D Bicket and DA Bass
During chemotherapy for acute leukemias, severe neutropenia allows
acquisition of life-threatening infections that are difficult to clear with
antibiotics alone. With return of myelopoiesis, even severe infections
often improve dramatically. We have sequentially examined oxidative
metabolic responses of polymorphonuclear leukocytes (PMNL) from 30 patients
with acute leukemias before induction chemotherapy and after recovery of
myelopoiesis (circulating PMNL greater than 500/microL). Maximal oxidative
metabolic responses were quantitated by flow cytometric analysis of
H2O2-dependent oxidation of intracellular 2',7'-dichlorofluorescin (DCFH)
in individual PMNL after stimulation with phorbol myristate acetate (PMA).
Resting PMNL oxidized a mean of 6.8 attomoles (amol) DCFH/cell/15 min, with
no difference between normal or patients' PMNL. PMA-stimulated normal PMNL
oxidized 183 +/- 35 amol/cell (mean +/- SD, n = 120). In patients' PMNL
obtained before chemotherapy, the mean DCFH oxidation was not significantly
different from controls (216 +/- 78 amol/cell). However, 11 of 22 samples
revealed populations of granulocytes with increased (primed) oxidative
responses; seven of these 11 patients had proven or suspected infection at
presentation. At recovery from chemotherapy-induced neutropenia, PMNL from
19 of 21 patients possessed one or more significant subpopulations with
primed oxidation in response to PMA. In these 19 patients, 61% +/- 8% of
PMNL comprised primed populations that oxidized 503 +/- 46 amol/cell.
Oxidative activity was most pronounced in patients with proven or
clinically suspected infections (with 41% +/- 9% of PMNL oxidizing 615 +/-
79 amol/cell). However, oxidative responses to PMA were also significantly
increased in recovery PMNL from ten patients without clinical or laboratory
evidence of active infection (79% +/- 11% of PMNL primed to oxidize 402 +/-
29 amol/cell). The peak responses of the primed subpopulations were
short-lived and generally lasted three days or less, although oxidative
responses remained elevated above normal for a week or more. All of the
patients with increased PMNL responsiveness survived their hospitalization.
In contrast, PMNL from four patients had a significant population (18% to
82% of cells) with reduced responsiveness. Two of these four patients (with
71% and 75% subnormal cells) died during this induction attempt; the third
died during a second induction attempt; only one survived to discharge. The
clinical significance of these phenomena is yet to be determined.(ABSTRACT
TRUNCATED AT 400 WORDS)
Volume 67,
Issue 6,
pp. 1624-1630,
06/01/1986
Copyright © 1986 by The American Society of Hematology
