CASE REPORT

Acute Respiratory Distress Syndrome Caused

by Leukemic Infiltration of the Lung
Yao-Kuang Wu,1 Yi-Chih Huang,2 Shiu-Feng Huang,3 Chung-Chi Huang,2* Ying-Huang Tsai2

Respiratory distress syndrome resulting from leukemic pulmonary infiltrates is seldom diagnosed ante-
mortem. Two 60- and 80-year-old women presented with general malaise, progressive shortness of breath,
and hyperleukocytosis, which progressed to acute respiratory distress syndrome (ARDS) after admission.
Acute leukemia with pulmonary infection was initially diagnosed, but subsequent examinations including
open lung biopsy revealed leukemic pulmonary infiltrates without infection. In one case, the clinical condi-
tion and chest radiography improved initially after combination therapy with chemotherapy for leukemia
and aggressive pulmonary support. However, new pulmonary infiltration on chest radiography and hypoxemia
recurred, which was consistent with acute lysis pneumopathy. Despite aggressive treatment, both patients
died due to rapidly deteriorating condition. Leukemic pulmonary involvement should be considered in
acute leukemia patients with non-infectious diffusive lung infiltration, especially in acute leukemia with
a high blast count. [J Formos Med Assoc 2008;107(5):419–423]

Key Words: acute lysis pneumopathy, acute respiratory distress syndrome, leukemia,
leukemic infiltration

Pulmonary complications, which occur during the distress syndrome (ARDS) before leukemia is di-
course of disease in nearly 80% of patients, are agnosed is rarely reported. Lung involvement as-
the major cause of death in leukemia.1 Pulmo- sociated respiratory failure is much less frequent
nary opportunistic infections2 and noninfectious in the early stage of the disease. Herein, we report
pulmonary abnormalities3 are the most common. two female patients who presented with ARDS
Symptomatic leukemic lung is the least common as the initial manifestation of undiagnosed acute
cause in leukemia patients. Definite diagnosis de- myeloid leukemia.
pends on investigations including bronchoalveolar
lavage (BAL),4 high-resolution chest tomography
(HRCT) or surgical lung biopsy.5 Acute respiratory Case Reports
failure caused by leukemic pulmonary involve-
ment in leukemia patients is commonly found Case 1
at autopsy, but only a few cases of pulmonary A 60-year-old female housekeeper was admitted
leukemic infiltration have been reported before in February 2002 after a month of intermittent
death, and all occurred after known leukemic his- fever, productive cough, and progressive short-
tory.5–9 Moreover, pulmonary leukemic infiltra- ness of breath. Vital signs were: body tempera-
tion as the initial presentation of acute respiratory ture (BT) 39°C; pulse rate 90 beats/min; blood

©2008 Elsevier & Formosan Medical Association

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1
Division of Pulmonary and Critical Care Medicine, Buddhist Tzu Chi General Hospital, Taipei, 2Division of Thoracic
Medicine and 3Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Received: August 28, 2006 *Correspondence to: Dr Chung-Chi Huang, Division of Thoracic Medicine, Chang Gung
Revised: May 3, 2007 Memorial Hospital, 5 Fu-Shin Street, Gueishan, Taoyuan, Taiwan.
Accepted: August 7, 2007 E-mail: cch4848@adm.cgmh.org.tw

J Formos Med Assoc | 2008 • Vol 107 • No 5 419

Y.K. Wu, et al

A B

C D

Figure 1. Chest radiography of case 1. (A) Air-space filling in bilateral lower lungs. (B) Extensive bilateral alveolar infiltration
with Swan-Ganz catheter and chest tube placement in the right lung. (C) Mild air-space filling in both lungs and much
improvement post chemotherapy. (D) Right pleural effusion, consolidation without air-bronchogram over both lungs.

pressure 130/70 mmHg; respiratory rate 25/min.
Initial hemogram showed: hemoglobin 3.2 mmol/
L; white blood cell count (WBC) 69 × 109/L with
79.5% blasts; platelet count 143,000/µL. Physical
examination at the time of admission revealed
pale conjunctiva, bibasilar lung coarse crackles
on auscultation, and soft abdomen without he-
patosplenomegaly. Chest X-ray showed bilateral
lower lung field infiltration (Figure 1A). Under
the impression of acute leukemia with pulmonary
infection, empiric antibiotics were given.
However, her condition deteriorated quickly.
WBC increased to 119 × 109/L on the fourth day
of hospitalization, and respiratory distress with
severe hypoxemia developed; arterial blood gas
on fractional concentration of inspired oxygen
(FiO2) 50% showed pH 7.426, PaCO2 45.2 mmHg,
PaO2 48.3 mmHg, and bicarbonate 29.7 mmol/L.
Chest X-ray revealed extensive diffuse infiltration
with pleural effusion in bilateral lung fields (Figure
1B). A Swan-Ganz catheter was inserted and pul-
monary wedge pressure was 12 mmHg. She was
intubated under the impression of ARDS and
transferred to the intensive care unit (ICU) on
the same day.
BAL was performed on the fifth day of hospi-
talization. However, all biological culture studies
were negative. Open lung biopsy was performed
on the seventh hospital day due to there being no
definite diagnosis after investigation, and pathol-
ogy revealed diffuse interstitial and perivascular
infiltration of blast cells in the lung tissue without
significant fibrosis or hyaline membrane forma-
tion (Figure 2A).
Bone marrow examination was performed later
and acute myeloid leukemia, M2, was diagnosed.

420 J Formos Med Assoc | 2008 • Vol 107 • No 5

 Leukemic pulmonary infiltrates in ARDS

A B

Figure 2. (A) Histopathologic examination of lung tissue shows heavy perivascular and interstitial infiltration of large
hyperchromatic white blood cells with abundant cytoplasm, consistent with myeloblast infiltration (hematoxylin & eosin,
200×). (B) Histopathologic examination of lung tissue shows widening of the alveolar septa due to diffuse interstitial
infiltration of large atypical white cells, consistent with myeloblast infiltration (hematoxylin & eosin, 200×).

Antileukemic chemotherapy with cyclophospha- count 76,000/µL. On physical examination, bi-

mide 1600 mg was started on the ninth day of
hospitalization, and the leukocyte count dropped
to 9.6 × 109/L 5 days later. Gas exchange improved
and lung infiltration resolved rapidly after che-
motherapy (Figure 1C); a program of weaning
from the ventilator was started.
Unfortunately, high fever and deteriorating
oxygenation developed and diffuse pulmonary in-
filtration recurred on the 16th hospital day (Figure
1D). A repeat bronchoscopy with iron stain ex-
amination from BAL on the same day disclosed
the etiology to be pulmonary hemorrhage rather
than an infectious origin. Due to severe hypoxemia,
the patient died in the ICU on the 18th day of
hospitalization. Lung necropsy revealed diffuse
alveolar damage and pulmonary hemorrhage.
Case 2
An 80-year-old woman with a history of diabetes
mellitus presented with cough, general weakness
and shortness of breath of a few days’ duration.
She was brought to our emergency room due to
loss of consciousness in February 2003. At the
time of admission, body temperature was 37°C,
pulse rate was 130 beats/min, blood pressure was
150/65 mmHg and respiratory rate was 26/min.
Initial hemogram showed: hemoglobin 8.4 mmol/
L; WBC 53 × 109/L with 76.5% blasts; platelet
basilar lung coarse crackles were heard on aus-
cultation, and the abdomen was soft without
hepatosplenomegaly. Chest X-ray revealed bilat-
eral lung field infiltration. Arterial blood gas with
FiO2 40% showed pH 7.3, PaO2 56.7 mmHg and
PaCO2 38 mmHg. She was transferred to the ICU
and intubated for mechanical ventilatory support
under the impression of acute leukemia and ARDS
of undetermined etiology.
Shock developed on the second day of ICU
admission. Inotropic agent and empiric antibiotics
were administered. Bone marrow examination later
confirmed her to have acute myeloid leukemia,
M5. All the culture and cytologic studies from
BAL showed negative findings. Unfortunately,
her condition deteriorated quickly and she died
on the sixth hospital day. Pathology from lung
necropsy showed widening of alveolar septa due
to infiltration of leukemic cells without signifi-
cant fibrosis or hyaline membrane formation
(Figure 2B).
Discussion
Acute respiratory failure related to leukemic pul-
monary infiltration or pulmonary leukostasis are
rarely confirmed before the diagnosis of leukemia.

J Formos Med Assoc | 2008 • Vol 107 • No 5 421

Y.K. Wu, et al
Leukemic pulmonary infiltration may progress
to ARDS in severe conditions. Both of our cases
present with pulmonary leukemic infiltration as
the initial manifestation of ARDS before leukemia
was diagnosed. In an autopsy study of the lung
in 50 acute leukemic patients, 66% were found to
have leukemic pulmonary infiltration, but only
two patients had symptoms.10 Many studies report
that infection is always considered in patients
with leukemia when respiratory symptoms occur.
The records of 139 adult patients with leukemia
were reviewed; most of the etiologies for the dif-
fuse pulmonary infiltration occurring at the time
of presentation or within the first 3 days of treat-
ment for leukemia were noninfectious.11 The bac-
teriologic study results of our two patients were
negative, and even the pathology of their open
lung biopsies did not have signs of infection.
Leukemic pulmonary involvement with leukemic
interstitial infiltration or intravascular leukostasis
may contribute to the respiratory distress syn-
drome. The leukemic cells infiltrate the peribron-
chial, perivascular interstitium, alveolar septa, or
pleura, and alveolar capillaries are plugged with
blast cells and microthrombi.12 The inelasticity of
blast cells lead to plugging of vascular channels
of capillary dimension.6
The diagnosis of leukemic pulmonary infil-
tration as the cause of acute respiratory failure
is based on pathologic or cytologic study after
excluding other common causes.13 Rossi et al re-
ported that the retrieval of leukemic cells by BAL
may establish the diagnosis, especially when the
platelet count is too low to be suitable for biopsy.10
No leukemic cells were seen in the lavage fluid
of our two cases, so BAL could not provide the
diagnosis of leukemic pulmonary infiltration.
However, the possibility of pulmonary leukemic
infiltration still could not be excluded. Leukemic
pulmonary infiltration should be suspected when
blast cells are > 40% in peripheral blood.1 Our
patients had peripheral blast counts of 79.5% and
76.5%, respectively, which correlate to the find-
ing in the above report. Consequently, leukemic
pulmonary infiltration should be highly suspected
when peripheral blast cell count is high or
422
increasing rapidly. The radiographic appearance of
pulmonary leukemic infiltrates is nonspecific and
variable, which may be normal in appearance,
focal homogeneous opacities, diffuse reticular-
nodular infiltration, or ground glass like alveolar
type filling opacities.1 In one study, less then 5%
of leukemic patients with leukemic pulmonary
infiltrates found postmortem had abnormal chest
radiographic findings.14 On HRCT, the most no-
table but nonspecific finding is thickening of the
interlobular septa and bronchovascular bundle.15
There has been no study to determine whether or
not the subtype of leukemia has differences in
pulmonary infiltration.
Our first patient experienced respiratory status
deterioration after initial chemotherapy consistent
with acute lysis syndrome, which included the
appearance of diffuse pulmonary infiltration that
coincided with a fall in leukocyte count following
chemotherapy, severe hypoxemia, and worsening
respiratory function.16–18 The pathologic change
was characterized by diffuse alveolar damage or
pulmonary hemorrhage.16 The syndrome may
occur within 7–20 days after chemotherapy, such
as hemorrhage or alveolar damage related to leu-
kemic cell lysis.17,18 The possible mechanisms
are upregulation of specific adhesion molecules
induced by chemotherapeutic agents that cause
aggregation of leukocytic thrombi, or the effects
of endothelial damage by protein synthesized
by leukemic cells and released during lysis.16,18
The pneumopathy may resolve without specific
therapy and profits from aggressive medical care
to overcome transient crisis. Some reports stressed
the need for evaluating pre-induction leukopho-
resis, and that most of the cases used cytosine
arabinoside as the base for multiple medical treat-
ment.19 However, the difference between our cases
and those reported in other papers was that we
only used cyclophosphamide as medical treat-
ment, but our cases showed acute lysis syndrome
as well.
One thing special about our cases is that before
acute leukemia was diagnosed, they had ARDS
as their first symptom. We confirmed it by open
lung biopsy and bone marrow examination. There
J Formos Med Assoc | 2008 • Vol 107 • No 5

are no clear clinical symptoms and imaging find-
ings for pulmonary leukemic infiltration, and the
results of treatment for patients with hemato-
logic malignancy who move into the ICU are not
very good.2 Therefore, it is very important to diag-
nose and initiate appropriate chemotherapy in the
early stages. It should be emphasized that leukemic
pulmonary infiltrates should be considered in all
leukemic patients with negative cultures, especially
in acute leukemia with a high blast count and
abnormal chest X-ray.
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