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THOMAS J. LESTER, M.D. Patients with acute myelocytic leukemia and hyperleukocytosis
JAMES W. JOHNSON, M.S. have a poor prognosis due to vascular leukostasis and infiltration
JANET CUTTNER, M.D. in the central nervous system and lungs. The clinical records of all
New York, New York patients with a new diagnosis of acute myelocytic leukemia and
initial white blood cell count greater than 100,000 X log/liter ad-
mitted to the Mount Sinai Medical Center between the years 1974
and 1983 were examined. Forty-three patients were identified, 22
of whom had clinical and/or pathologic evidence of leukostasis of
the central nervous system and/or lung. All patients received in-
duction chemotherapy with daunorubicin and a continuous infusion
of cytosine arabinoside. Thirty-five patients also underwent thera-
peutic leukapheresis prior to induction chemotherapy. The overall
remission induction rate in these 43 patients was 51 percent. Fifteen
patients had lung leukostasis; the remission rate for these patients
was 27 percent (three complete remlssions, one partial remission),
as compared with a remission rate of 64 percent (18 of 28) for those
without pulmonary leukostasis (x: = 5.53; p = 0.02). Thirteen pa-
tients had central nervous system infiltration; the remission rate for
these patients was 46 percent (five complete remissions, one partial
remission), as compared with 53 percent (16 of 30) for patients
without central nervous system involvement (x: = 0.19; p = 0.67).
The median survival of 21 patients without leukostasls was 10.8
months, as compared with 15.4 months for seven patients with
central nervous system involvement and no lung leukostasis and 0.2
months for 15 patients with pulmonary leukostasis (xz = 19.9; p
<O.OOl). Thus, pulmonary leukostasis was found to be the single
worst prognostic factor in this group of patients.
0.10; log rank XT = 3.58, p = 0.06). The effect of the lung leukostasis with or without central nervous system
height of the initial white blood cell count above infiltration (15 patients, median survival 0.2 months);
lOO,OOO/~l on survival was examined using the Cox those with central nervous system infiltration alone
regression model. The result showed no significant in- (seven patients, median survival 15.4 months); and
fluence of white blood cell count on survival. those having neither lung nor central nervous system
The survival curves for patients with lung leukostasis involvement (2 1 patients, median survival 10.8 months).
and for those with central nervous system infiltration Comparison of the curves in Figure 4 shows a highly
are shown in Figures 2 and 3, respectively. Figure 4 significant difference (Wilcoxon xg = 20.7, p <O.OOl;
shows the survival curves of three groups: those having log rank xz = 20.5, p <O.OOl).
I I I I I I I I I
2 1.0 b
L
2 0.8
2
r’ 0.2
= 0
_I!-I
With CNS
= 0.2 op-TIJ....
-Tljnftltrat~on -..on
3 t I I I I I
‘b-2
0-w-m
-I l
e-e e __-- _-_--___
== 0 I I I I I I _-_ ___-- -----_-_ I ,-I
4 8 12 I6
I2 16 20 2: 28 32 36 40 Figure 3. Comparative survival in pa-
tients with and without central nervous
TIME IN MONTHS system (CPJS) infiltration.
1.o
0.8
0.6
Without leukemic
0.4 involvement of
0.2
mend immediate arterial blood analysis performed in kapheresis before cytotoxic agents are administered.
the respiratory intensive care unit, in order to avoid We [8] have evaluated leukapheresis in 22 of the pa-
prolonged transport, mishandling by technicians, and tients described herein, and found that success in
the requisite oxygen consumption inherent in the lowering the white blood cell count was an important
cooling and rewarming of specimens. predictor of response. Fifteen of 17 patients with greater
The frequency of cases of monocytic leukemia in than 30 percent reduction in the initial white blood cell
those patients with infiltrations of parenchyma was not count had remission, whereas none of five with stable
unexpected [ 131. We [ 141 found seven of 39 consec- or increasing hyperleukocytosis had responses (p =
utive patients with newly diagnosed acute myelocytic 0.001).
leukemia to have central nervous system involvement Utilizing readily obtainable clinical data, i.e., symp-
as evidenced by cytocentrifuge examination of cere- toms, findings on physical examination, arterial blood
brospinal fluid. All seven patients had myelomonocytic gas values, and chest radiographic results, we have
leukemia (M4). Monocytic blasts seem particularly identified a subgroup of patients with acute myelocytic
prone to aggregate and invade parenchyma. leukemia and hyperleukocytosis-those with pulmonary
Four patients of Myers et al [ 151 and five patients of leukostasis-who are largely responsible for the high
Tryka et al [ 161 had acute myelocytic leukemia and mortality rate. This subgroup is in sharp contrast to the
acute respiratory failure following cytotoxic chemo- unaltered initial response rate of patients with infiltration
therapy. Pulmonary tissue demonstrated vascular en- of the central nervous system. Although therapeutic
gorgement/leukemic infiltration in all cases. They leukapheresis may improve survival in patients whose
proposed leukemic cell lysis with release of endoge- white blood cell count can be controlled, those with
nous pyrogen, proteolytic enzymes, and procoagulant rapid return of the leukocytosis to pretreatment levels
material as responsible for this clinical picture. Tryka seem not to be helped. Therapy in these patients should
et al demonstrated degenerating blasts in the pulmonary be directed at aggressive pulmonary support and re-
parenchyma by immunoperoxidase staining of biopsy duction of the hyperleukocytosis as rapidly as possible.
specimens. In contrast, the clinical picture of pulmonary Innovative approaches in removal of leukemic blasts
toxicity developed in only one of our patients following without exposing vital organs to the products of cellular
chemotherapeutic lysis. This may be related to our lysis may reduce the lethal consequences of current
treatment approach with aggressive therapeutic leu- cytotoxic therapy.
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