J. Graham,
Nancy
MD
#{149} Nestor
Intrathoracic Bone Marrow
L. Muller,
terms:
Bone
Computed studies 60.458 Radiology
marrow,
Lung,
1991;
(CT), comparative CT, 60.1211 #{149} Lung, diseases,
181:153-156
From the Departments N.L.M.) and Pathology
mia-Bone
transplantation
tomography #{149}
Marrow
of Radiology (N.J.G., (R.R.M.) and the Leuke-
Transplant
Program
PhD
#{149} Roberta
R. Miller,
Complications Transplantation:
The authors retrospectively reviewed computed tomographic (CT) scans of 18 patients who developed 21 episodes of intrathoracic complications after allogeneic bone marrow transplantation (BMT). Pathologic and/or microbiologic diagnoses were available for all patients. All patients were immunocompromised due to either graft-versus-host disease (GVHD), neutropenia, or recurrent malignancy after BMT. CT demonstrated diagnostically relevant findings that were not apparent at radiography in 12 of the 21 cases (57%). These included a ground-glass pattern in early pneumonia (n = 5); a peripheral dlistribution in GVHD, bronchiolitis obliterans organizing pneumonia, and eosinophilic drug reaction (n = 4); cavitating lesions in Pneumocystis carinii pneumonia (n = 1); hemorrhagic infarcts in aspergillosis (n = 1); and mediastinal adenopathy in recurrent Hodgkin disease (n = 1). The authors conclude that chest CT is superior to radiography in demonstrating the presence, distribution, and extent of intrathoracic complications developing in patients after allogeneic BMT. CT is useful in guiding procedures for tissue diagnosis. Index
MD,
of Brit-
ish Columbia (J.D.S.), University of British Columbia and Vancouver General Hospital, 855 W 12th Ave. Vancouver, BC, Canada V5Z 1M9. From the 1990 RSNA scientific assembly. Received March 14, 1991; revision requested April 11; revision received April 25; accepted May 3. Address reprint requests to N.L.M. 0 RSNA, 1991
A
MD
bone marrow transplantation (BMT) is performed as part of treatment for a variety of potentially fatal hematobogic and immunologic disorders. Pulmonary complications are a common cause of both serious morbidity and mortality after allogeneic BMT (1-7). These complications include infection, graftversus-host disease (GVHD), reactions to drugs, pulmonary vascular and
direct
lung
toxic
reactions from preconditioning regimens of chemotherapy and wholebody irradiation, transient pulmonary edema, adult respiratory distress syndrome, pulmonary hemorrhage, and recurrent malignancy (1-10). The radiographic findings of these complications are variable and often indistinguishable
from
one
another
(3).
The aims of the present study were to assess the computed tomographic (CT) appearance of the intrathoracic complications of allogeneic BMT and compare the results of CT with the radiographic
D. Shepherd,
and
pathologic
findings.
ings
or when
Twenty-one
AND separate
METHODS intrathoracic
com-
plications in 18 patients (11 men and seven women) who received allogeneic bone marrow transplants between November 1985 and November 1990 were induded in the study. The age range of the patients at transplantation was 19-47 years (mean, 32 years). All patients underwent BMT for a hematobogic malignancy (leukemia or preleukemia, n = 14; Hodgkin disease, n = 2; non-Hodgkin bymphoma, n = 1; and multiple myeboma, n = 1). All patients were immunocompromised due to GVHD (n = 12), neutropenia (n = 3), a combination of GVHD and neutropenia (n = 2), or recurrent Hodgkin disease (n = 1). Chest radiographs in patients with a bone marrow transplant were performed at the first indication of any pulmonary complication and daily when the patient was febrile. CT scans were obtained when the patients had major pulmonary symptoms without definite radiographic find-
a tissue
diagnosis
was
mdi-
cated. CT is performed almost routinely before open lung biopsy at our institution to guide the surgeon to the optimal biopsy site(s).
CT scans were obtained on a GE 9800 scanner (GE Medical Systems, Milwaukee) at 120 kVp and 340-420 mAs. Scans were obtained with use of 10-mm collimation (n = 4), 1.5-mm collimation (n = 10), or both 10- and 1.5-mm collimation (n = 7). The 10-mm coffimation scans were obtained at 10-mm intervals through the chest. The I .5-mm sections were obtained at 20-mm intervals and reconstructed with use of a high-spatial-frequency (n = 15) or standard (n = 2) algorithm. Additional 1.5mm-collimation scans were obtained through the site(s) of suspected abnormality based on the chest radiograph in four patients. Images were obtained at window levels and widths appropriate for assessing lung parenchyma (bevel, -600 to -700 HU; width, 1,000-2,000 HU) and mediastinum (bevel, 30-60 HU; width, 300-500 HU). Comparison chest radiographs (standard departmental posteroanterior and lateral radiographs, n = 14; anteroposterior radiographs acquired on a portable unit, n = 7) were obtained within a maximum of 3 days of chest CT. The chest radiographs
PATIENTS
MD
Following Allogeneic CT Findings’
LLOGENEIC
abnormalities
#{149} John
and
chest
viewed
independently
(N.J.G.,
N.L.M.),
reached
and
by means
Pathologic
noses
were
opsy
enabled
and/or
available
CT scans were reby two observers the final decision was
of consensus. microbiologic
diag-
for all 21 cases.
the diagnosis
Bi-
in 16 cases
(14
open lung, one transbronchial, one anterior mediastinotomy). Three diagnoses were achieved by means of bronchoscopy with brushing one diagnosis was achieved by means of fine-needle aspiralion and another by means of postmortem examination. All but one of the pathologic specimens were prosected by the same pathologist
(R.R.M.).
The intrathoracic oped 1-30 months (median, 5 months).
complications devebafter transplantation Thirteen
of the
21
BMT = bone marrow transplantation, BOOP = bronchiolitis obliterans organizing pneumonia, GVHD = graft-versusAbbreviations:
host
disease.
153
a.
complications
had
an
infectious
cases cases
of bacterial pneumonia due to Pseudomonas
cases case
RESULTS
cause.
These developed 1-30 months plantation (median, 6 months).
after transThe six included
two
aeruginosa,
two
to Staphylococcus aureus, and due to Streptococcus viridans
due each
one and
an enterococcus (Streptococcus fecalis). One case of fungal pneumonia developed due to Aspergillus fumigatus. Two cases of combined bacterial and fungal pneumonia occurred, due to mixed gram-negative bacilli plus Candida albicans in one case and due to P aeruginosa and A fumigatus in the other
case. Three cases of Pneumocystis carinii pneumonia developed 3, 12, and 13 months after transplantation in patients with chronic GVHD. Herpes simplex virus pneumonia represented the tious pulmonary complication.
13th Ten
infecof the
13 patients in whom infectious complications developed had clinical and/or pathologic
evidence
were
neutropenic,
of GVHD,
both
GVHD
two
and
and
one
patients
patient
had
GVHD following
plantation.
patients
One
of these
devebtrans-
had cmi-
cal and pathologic evidence of GVHD involving other organs (gastrointestinal tract and skin) in addition to the lungs, while the other patient had minimal
GVHD except in the lungs. One developed localized bronchiobitis ans
organizing
pneumonia
of the
never determined; he simultaneously veloped mild gastrointestinal GVHD.
deTwo
patients developed pulmonary and 6 weeks, respectively, after
3 Both
underwent were
open
febribe,
chymal diuretic
lung
and
abnormalities therapy.
an eosinophilic
One
persisted patient
pulmonary and
(Septra;
Burroughs
Canada)
5 months
reaction
Another
patient drug
transplantation
developed year
154
after
after
that
#{149} Radiology
was
reaction
One
patient
disease
(Fig
1
b. Figure
1.
CT
months shows
after allogeneic BMT. (a) Radiograph no evidence of lymphadenopathy.
case,
the left
of
even in abnormalpresence
superior
of
paratra-
1) 12 months
after
information
one case-a parenchymal erally
in seven
wedge-shaped,
based
right
infarct evident not
In
periph-
middle
lobe
hemor-
due to Afumigatus on the CT scan
was
readily
diograph. bacterial
ad-
cases.
patient with extensive scarring from previous
infections-a
yet the raof the six cases of (two cases of
apparent
In three pneumonia
on
numerous small cystic lesions that were not apparent on the radiograph; these lesions were proved to be due to P carinii pneumonia (Fig 3). A peripheral
clearly
abnormal,
extensive
scarring
the and
(Fig better
demonstrating
secondary
to previ-
Acute abnormalities apparent (n = 2) or
radiographs; demonstrated
2). The
diagnosis
of pneumo-
ground-glass
delineated
on
pattern high-resolu-
demonstrated
philic
drug
two two
cases cases
not
was
of pulmonary of bacterial
demonstrated distribution
apparent
one
case
on
not apparIn addition, GVHD broncho-
an obvious at CT that the
radiographs.
CT findings confirmed the abnormalities identified on radiographs but did
not
provide
significant
additional
information in nine of the 21 cases. These included three cases of bacteriab pneumonia, one case of combined
nia,
herpes
were
reaction
pneumonia peribronchiab
bacterial
abnormalities
GVHD,
case of an eosino(Fig 4). This pe-
ripheral distribution ent on the radiographs.
tion than on conventional CT scans. In one case of early P carinii pneumoparenchymal
distribution was at CT in two
of pulmonary of BOOP, and one
was
2) on
and extent of a groundin these four cases, con-
the
12
questionable on the radiograph; however, an extensive ground-glass pattern was clearly identified on the CT scan, consistent with early pneumonia. In another case, CT demonstrated
markedly
with
man
Conventional CT scan (10-mm colbimation) demonstrates enlarged left superior paratracheal lymph node (region 2L) (arrow), which at anterior mediastinotomy demonstrated recurrent Hodgkin disease.
cases
(n = CT clearly
of 20-year-old
0’)
P aeruginosa infection and one case of S aureus infection) and in one case of mixed bacterial and fungab pneumonia (P aeruginosa and A fumigatus infection), the underlying lungs were
not
Images
BMT.
Among the 13 infectious pulmonary complications, CT provided
was
after
CT scans
cheal lymph node and several i-cmdiameter lower paratracheab nodes that were pathologically confirmed to represent recurrent Hodgkin disease
nia
a cytotoxic fatal.
demonstrated
a 2-cm-diameter
sistent
to therapy.
this
In
the presence glass pattern
transplantation;
Hodgkin
clearly
however,
Calgary,
I month
apparent.
ous infections. were either questionable
trimethoprim
developed
recurrent BMT.
drug
well
reaction
they
parendespite developed
Weilcome,
responded
pulmonary
because
pulmonary
to sulfamethoxazole
this
biopsy
the
chest
disease, on which, no radiographic
was
was
right upper lobe 2 months after transplantation, the precise cause of which was
edema BMT.
ity
rhagic clearly
patient obliter-
(BOOP)
Hodgkin retrospect,
ditional
neutropenia.
Two cases of pulmonary oped at 9 and 1 1 months
In 12 of the 21 cases,
demonstrated diagnostically significant findings not apparent on chest radiographs (Table). All radiographs included in this study were abnormal, except those the one patient with recurrent
case
and
each
fungab
of P carinii
virus
pneumonia,
pneumonia,
one
pneumonia
and
one
case
of a
October
1991
a. Figure
3.
CT scan
algorithm) cabized sions
cystic were
C.
Figure
2.
Images
of 49-year-old
developed fever and BMT. (a) Radiograph
man
who
cough 2 years after is abnormal, demon-
strating bilateral areas of scarring, particularly in the middle and lower lung zones. The radiographic findings, however, had not changed over the previous 3 months. (b) High-resolution CT scan (1.5-mm collimation with use of high-spatial-frequency reconstruction algorithm) obtained at level of aortic arch shows a bilateral ground-glass pattern. Mild parenchymal scarring can be seen in the posterior aspect of the right upper lobe. (c) High-resolution CT scan through the lung bases shows more extensive scarring and cylindrical bronchiectasis
but only
minimal
ground-glass
pattern.
On
the basis of the CT findings, bronchoalveolar lavage was performed in the right upper lobe and demonstrated the presence of P aeruginosa pneumonia.
cytotoxic
drug
of pulmonary
reaction,
and
two
cases
edema.
DISCUSSION The intrathoracic that occur following
complications allogeneic
are
a major
diverse
Volume
and
181
are
#{149} Number
1
cause
BMT of
areas
not
ground-glass
b.
(1.5-mm
collimation,
of 37-year-old in both
apparent
pattern
on
upper
lobes
the
radiograph.
on the radiograph
morbidity and mortality (4-10). Although chest radiography is performed routinely in these patients and often gives the first clue to the presence of intrathoracic complications, it has low sensitivity and specificity (3). In the present evaluation of 21 intrathoracic complications in 18 BMT recipients, chest CT demonstrated additional findings that were not apparent on radiographs in 57% of cases. CT was particularly useful in the case of recurrent Hodgkin disease. Radiography demonstrated no abnormality, but CT demonstrated mediastinab lymphadenopathy, which proved to be recurrent Hodgkin disease. Pneumonias complicate a significant number of transplantations (1,6) and may develop early ( < 100 days) and late ( > 100 days) after transplantation (5). In the present study, pneumonias
accounted
for
13 of the
standard
reconstruction
man with P carinii pneumonia
21
(arrows). The
and
These patient
shows iocystic lealso
had
a
CT scan.
distribution pattern was not specific and was found in occasional cases of infection and other noninfectious complications. Pulmonary edema is a recognized early complication of BMT (5,7). Often the diagnosis can be readily made. Pulmonary edema may, however, manifest with atypical clinical and radiologic findings; the diagnosis then requires open lung biopsy. Our study included two such cases; CT did not provide additional information in either case. The absence of any patients with cytomegabovirus pneumonia from this study is due to two factors. First, although cytomegabovirus pneumonia is reported to be a frequent respiratory complication of BMT (4,5), it is relatively uncommon at our institution. Second, the few cases that we have seen in BMT recipients demonstrated symptoms
the
classic constellation and signs (dyspnea,
of fever,
complications. CT provided useful additional information in seven of these cases, either by demonstrating early small lesions not apparent on radiographs or by demonstrating acute changes superimposed on chronic lung disease. Thus, CT may be particularly useful in a patient without definite new radiographic abnormalities in whom an acute pubmonary episode is suspected clinically. Pulmonary GVHD and BOOP are
bilateral infiltrates in the appropriate clinical setting (ie, 6-12 weeks after transplantation in cytomegalovirusseropositive patients who had acute GVHD). The diagnosis was therefore strongly suspected clinically, and, as the patients were extremely ill, rapid pathologic confirmation was obtained bronchoscopically without obtaining a prior chest CT scan. Patient selection probably also accounted, at least in part, for the high yield of CT find-
well-recognized
ings was
complications
in
long-term survivors of BMT (5,11,12). In the present study, the peribronchial and peripheral distribution of these abnormalities was not apparent on radiographs but was clearly demonstrated on CT scans. However, this
severe hypoxemia, on the radiograph)
not apparent performed
at radiography. in patients with
CT fever
and pulmonary symptoms but normal or questionable radiographic findings and before invasive procedures such as open lung biopsy. Although this point
was
not
Radiology
specifi#{149} 155
a. Figure
b. 4.
Images
of 22-year-old
man
with
severe
dyspnea
and
dry
cough
1 year
level of right upper lobe bronchus shows penbronchiai (arrows) and subpleural peripheral distribution at lung bases. Open lung biopsy demonstrated GVHD.
cabby addressed in this study, it has been shown that CT is useful in immunocompromised patients undergoing open lung biopsy (13,14). In this population, the object of the procedure is to sample areas of most severe involvement because these are most likely to be diagnostic (14). As CT is superior to radiography in determining both the distribution and the extent of active disease, it is more helpful in planning appropriate biopsy sites.
CT
is performed
almost
rou-
tineby before open lung biopsy at our institution. No specific attempt was made in this study to compare conventional with high-resolution CT. However, the ground-glass pattern present in patients with early pneumonia was better delineated on high-resolution CT scans. This is in keeping with the results of previous studies (15,16). Recently, Leung et al demonstrated that in patients with chronic diffuse infiltrative lung disease, a limited number of high-resolution CT scans can provide a diagnostic accuracy similar to that of complete conventional CT scanning (17). Obviously, if the examination is limited to a small number of high-resolution CT scans, focal parenchymab abnormalities and small nodules may be missed. Therefore, the optimal kind of examination, whether high-resolution CT or a combination of conventional and high-resolution CT, depends on the clinical situation.
156
#{149} Radiology
after
allogeneic
consolidation.
At our institution, the limited availability of CT scanner time also has an important effect on technique, because patients with intrathoracic complications following allogeneic BMT usually require CT within 24 hours of admission. Therefore, in these patients, we currently obtain high-resolution CT scans at 10- or 20-mm intervals through the chest, complemented by one or more images at bevels in which abnormalities are suspected on the chest radiograph. Only when assessing
for
possible
presence
of a tu-
mor do we perform complete conventional CT in these patients. In conclusion, although chest CT will probably not provide the definitive diagnosis in most intrathoracic complications of allogeneic BMT, it is superior to chest radiography in demonstrating the presence and extent of these abnormalities. CT should be performed before any invasive diagnostic procedure such as open lung biopsy
optimal
to guide
the
biopsy
site.
surgeon
BMT.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
to the
#{149}
15.
References 1.
2.
3.
Solberg CO, Meuwissen HJ, Needham RN, Good RA, Matsen JM. Infectious complications of bone marrow transplant patients. Br MedJ 1971; 1:18-23. Winston DJ, Gale RP, Meyer DV, Young LS, and the UCLA Bone Marrow Transplant Group. Infectious complications of human bone marrow transplantation. Medicine 1979; 58:1-31. Wise RHJr, Shin MS. Gockerman JP, Zornes SL, Rubin E, Nath PH. Pneumonia in bone marrow transplant patients. AJR 1984; 143:
(a) High-resolution
(b) Ten-millimeter-collimation
16.
17.
CT
scan
obtained
at
CT scan shows
Hamilton PJ, Pearson ADJ. Bone marrow transplantation and the lung. Thorax 1986; 41 :49’-502. Bombi JA, Cardesa A, Llebaria C, et al. Main autopsy findings in bone marrow transplant patients. Arch Pathol Lab Med 1987; 3:125-129. Dickout WJ, Chan CK, Hyland RH, et al. Prevention of acute pulmonary edema after bone marrow transplantation. Chest 1987; 92:303309. El-Khatib EE, Freeman CR, Rybka WB, Lehnert s, Podgorsak EM. The use of CT densitometry to predict lung toxicity in bone marrow transplant patient. mt j Radiat Oncol Biol Phys 1989; 16:85-94. Allen BT, Day DL, Dehner LP. CT demonstration of asymptomatic pulmonary emboli after bone marrow transplantation: case report. Pediatr Radiol 1987; 17:65-67. Allan BT, Patton D, Ramsey NKC, Day DL. Pulmonary fungal infections after bone marrow transplantation. Pediatr Radiol 1988; 18: 118-122 McLoud TC, Epler GR, Colby TV, Gaensler EA, Carrington CB. Bronchiolitis obliterans. Radiology 1986; 159:1-8. Muller NL, Staples CA, Miller RR. Bronchiolitis obliterans organizing pneumonia: CT feahires in 14 patients. AIR 1990; 154:983-987. Kuihman JE, Fishman EK, Meziane MA, Khouri NF, Zerhouni EA, Siegelman SS. CT diagnosis of opportunistic chest infections in the immunocompromised host with CT-pathologic correlation (abstr). Radiology 1986; 161(P):390. Miller RR, Nelems B, Muller NL, Evans KG, Ostrow DN. Lingular and right middle lobe biopsy in the assessment of diffuse lung disease. Ann Thorac Surg 1987; 44:269-273. Muller NL, Staples CA, Miller RR, Vedal 5, Thurlbeck WM, Ostrow DN. Disease activity in idiopathic pulmonary fibrosis: CT and pathologic correlation. Radiology 1987; 165: 731-734. Mathieson JR. MayoJR, Staples CA, Muller NL. Chronic diffuse infiltrative lung disease: comparison of diagnostic accuracy of CT and st radiography. Radiology 1989; 171:111Leung AN, Staples CA, Muller NL. Chronic diffuse infiltrative lung disease: comparison diagnostic accuracy ofhigh-resolution and conventional CT. AIR (in press).
of
707-714.
4.
Krowka MJ, Rosenow EC, Hoaglund HC. Pulmonary complications of bone marrow transplantation. Chest 1985; 87:237-246.
October
1991
Nancy
MD
#{149} Nestor
Intrathoracic Bone Marrow
L. Muller,
terms:
Bone
Computed studies 60.458 Radiology
marrow,
Lung,
1991;
(CT), comparative CT, 60.1211 #{149} Lung, diseases,
181:153-156
From the Departments N.L.M.) and Pathology
mia-Bone
transplantation
tomography #{149}
Marrow
of Radiology (N.J.G., (R.R.M.) and the Leuke-
Transplant
Program
PhD
#{149} Roberta
R. Miller,
Complications Transplantation:
The authors retrospectively reviewed computed tomographic (CT) scans of 18 patients who developed 21 episodes of intrathoracic complications after allogeneic bone marrow transplantation (BMT). Pathologic and/or microbiologic diagnoses were available for all patients. All patients were immunocompromised due to either graft-versus-host disease (GVHD), neutropenia, or recurrent malignancy after BMT. CT demonstrated diagnostically relevant findings that were not apparent at radiography in 12 of the 21 cases (57%). These included a ground-glass pattern in early pneumonia (n = 5); a peripheral dlistribution in GVHD, bronchiolitis obliterans organizing pneumonia, and eosinophilic drug reaction (n = 4); cavitating lesions in Pneumocystis carinii pneumonia (n = 1); hemorrhagic infarcts in aspergillosis (n = 1); and mediastinal adenopathy in recurrent Hodgkin disease (n = 1). The authors conclude that chest CT is superior to radiography in demonstrating the presence, distribution, and extent of intrathoracic complications developing in patients after allogeneic BMT. CT is useful in guiding procedures for tissue diagnosis. Index
MD,
of Brit-
ish Columbia (J.D.S.), University of British Columbia and Vancouver General Hospital, 855 W 12th Ave. Vancouver, BC, Canada V5Z 1M9. From the 1990 RSNA scientific assembly. Received March 14, 1991; revision requested April 11; revision received April 25; accepted May 3. Address reprint requests to N.L.M. 0 RSNA, 1991
A
MD
bone marrow transplantation (BMT) is performed as part of treatment for a variety of potentially fatal hematobogic and immunologic disorders. Pulmonary complications are a common cause of both serious morbidity and mortality after allogeneic BMT (1-7). These complications include infection, graftversus-host disease (GVHD), reactions to drugs, pulmonary vascular and
direct
lung
toxic
reactions from preconditioning regimens of chemotherapy and wholebody irradiation, transient pulmonary edema, adult respiratory distress syndrome, pulmonary hemorrhage, and recurrent malignancy (1-10). The radiographic findings of these complications are variable and often indistinguishable
from
one
another
(3).
The aims of the present study were to assess the computed tomographic (CT) appearance of the intrathoracic complications of allogeneic BMT and compare the results of CT with the radiographic
D. Shepherd,
and
pathologic
findings.
ings
or when
Twenty-one
AND separate
METHODS intrathoracic
com-
plications in 18 patients (11 men and seven women) who received allogeneic bone marrow transplants between November 1985 and November 1990 were induded in the study. The age range of the patients at transplantation was 19-47 years (mean, 32 years). All patients underwent BMT for a hematobogic malignancy (leukemia or preleukemia, n = 14; Hodgkin disease, n = 2; non-Hodgkin bymphoma, n = 1; and multiple myeboma, n = 1). All patients were immunocompromised due to GVHD (n = 12), neutropenia (n = 3), a combination of GVHD and neutropenia (n = 2), or recurrent Hodgkin disease (n = 1). Chest radiographs in patients with a bone marrow transplant were performed at the first indication of any pulmonary complication and daily when the patient was febrile. CT scans were obtained when the patients had major pulmonary symptoms without definite radiographic find-
a tissue
diagnosis
was
mdi-
cated. CT is performed almost routinely before open lung biopsy at our institution to guide the surgeon to the optimal biopsy site(s).
CT scans were obtained on a GE 9800 scanner (GE Medical Systems, Milwaukee) at 120 kVp and 340-420 mAs. Scans were obtained with use of 10-mm collimation (n = 4), 1.5-mm collimation (n = 10), or both 10- and 1.5-mm collimation (n = 7). The 10-mm coffimation scans were obtained at 10-mm intervals through the chest. The I .5-mm sections were obtained at 20-mm intervals and reconstructed with use of a high-spatial-frequency (n = 15) or standard (n = 2) algorithm. Additional 1.5mm-collimation scans were obtained through the site(s) of suspected abnormality based on the chest radiograph in four patients. Images were obtained at window levels and widths appropriate for assessing lung parenchyma (bevel, -600 to -700 HU; width, 1,000-2,000 HU) and mediastinum (bevel, 30-60 HU; width, 300-500 HU). Comparison chest radiographs (standard departmental posteroanterior and lateral radiographs, n = 14; anteroposterior radiographs acquired on a portable unit, n = 7) were obtained within a maximum of 3 days of chest CT. The chest radiographs
PATIENTS
MD
Following Allogeneic CT Findings’
LLOGENEIC
abnormalities
#{149} John
and
chest
viewed
independently
(N.J.G.,
N.L.M.),
reached
and
by means
Pathologic
noses
were
opsy
enabled
and/or
available
CT scans were reby two observers the final decision was
of consensus. microbiologic
diag-
for all 21 cases.
the diagnosis
Bi-
in 16 cases
(14
open lung, one transbronchial, one anterior mediastinotomy). Three diagnoses were achieved by means of bronchoscopy with brushing one diagnosis was achieved by means of fine-needle aspiralion and another by means of postmortem examination. All but one of the pathologic specimens were prosected by the same pathologist
(R.R.M.).
The intrathoracic oped 1-30 months (median, 5 months).
complications devebafter transplantation Thirteen
of the
21
BMT = bone marrow transplantation, BOOP = bronchiolitis obliterans organizing pneumonia, GVHD = graft-versusAbbreviations:
host
disease.
153
a.
complications
had
an
infectious
cases cases
of bacterial pneumonia due to Pseudomonas
cases case
RESULTS
cause.
These developed 1-30 months plantation (median, 6 months).
after transThe six included
two
aeruginosa,
two
to Staphylococcus aureus, and due to Streptococcus viridans
due each
one and
an enterococcus (Streptococcus fecalis). One case of fungal pneumonia developed due to Aspergillus fumigatus. Two cases of combined bacterial and fungal pneumonia occurred, due to mixed gram-negative bacilli plus Candida albicans in one case and due to P aeruginosa and A fumigatus in the other
case. Three cases of Pneumocystis carinii pneumonia developed 3, 12, and 13 months after transplantation in patients with chronic GVHD. Herpes simplex virus pneumonia represented the tious pulmonary complication.
13th Ten
infecof the
13 patients in whom infectious complications developed had clinical and/or pathologic
evidence
were
neutropenic,
of GVHD,
both
GVHD
two
and
and
one
patients
patient
had
GVHD following
plantation.
patients
One
of these
devebtrans-
had cmi-
cal and pathologic evidence of GVHD involving other organs (gastrointestinal tract and skin) in addition to the lungs, while the other patient had minimal
GVHD except in the lungs. One developed localized bronchiobitis ans
organizing
pneumonia
of the
never determined; he simultaneously veloped mild gastrointestinal GVHD.
deTwo
patients developed pulmonary and 6 weeks, respectively, after
3 Both
underwent were
open
febribe,
chymal diuretic
lung
and
abnormalities therapy.
an eosinophilic
One
persisted patient
pulmonary and
(Septra;
Burroughs
Canada)
5 months
reaction
Another
patient drug
transplantation
developed year
154
after
after
that
#{149} Radiology
was
reaction
One
patient
disease
(Fig
1
b. Figure
1.
CT
months shows
after allogeneic BMT. (a) Radiograph no evidence of lymphadenopathy.
case,
the left
of
even in abnormalpresence
superior
of
paratra-
1) 12 months
after
information
one case-a parenchymal erally
in seven
wedge-shaped,
based
right
infarct evident not
In
periph-
middle
lobe
hemor-
due to Afumigatus on the CT scan
was
readily
diograph. bacterial
ad-
cases.
patient with extensive scarring from previous
infections-a
yet the raof the six cases of (two cases of
apparent
In three pneumonia
on
numerous small cystic lesions that were not apparent on the radiograph; these lesions were proved to be due to P carinii pneumonia (Fig 3). A peripheral
clearly
abnormal,
extensive
scarring
the and
(Fig better
demonstrating
secondary
to previ-
Acute abnormalities apparent (n = 2) or
radiographs; demonstrated
2). The
diagnosis
of pneumo-
ground-glass
delineated
on
pattern high-resolu-
demonstrated
philic
drug
two two
cases cases
not
was
of pulmonary of bacterial
demonstrated distribution
apparent
one
case
on
not apparIn addition, GVHD broncho-
an obvious at CT that the
radiographs.
CT findings confirmed the abnormalities identified on radiographs but did
not
provide
significant
additional
information in nine of the 21 cases. These included three cases of bacteriab pneumonia, one case of combined
nia,
herpes
were
reaction
pneumonia peribronchiab
bacterial
abnormalities
GVHD,
case of an eosino(Fig 4). This pe-
ripheral distribution ent on the radiographs.
tion than on conventional CT scans. In one case of early P carinii pneumoparenchymal
distribution was at CT in two
of pulmonary of BOOP, and one
was
2) on
and extent of a groundin these four cases, con-
the
12
questionable on the radiograph; however, an extensive ground-glass pattern was clearly identified on the CT scan, consistent with early pneumonia. In another case, CT demonstrated
markedly
with
man
Conventional CT scan (10-mm colbimation) demonstrates enlarged left superior paratracheal lymph node (region 2L) (arrow), which at anterior mediastinotomy demonstrated recurrent Hodgkin disease.
cases
(n = CT clearly
of 20-year-old
0’)
P aeruginosa infection and one case of S aureus infection) and in one case of mixed bacterial and fungab pneumonia (P aeruginosa and A fumigatus infection), the underlying lungs were
not
Images
BMT.
Among the 13 infectious pulmonary complications, CT provided
was
after
CT scans
cheal lymph node and several i-cmdiameter lower paratracheab nodes that were pathologically confirmed to represent recurrent Hodgkin disease
nia
a cytotoxic fatal.
demonstrated
a 2-cm-diameter
sistent
to therapy.
this
In
the presence glass pattern
transplantation;
Hodgkin
clearly
however,
Calgary,
I month
apparent.
ous infections. were either questionable
trimethoprim
developed
recurrent BMT.
drug
well
reaction
they
parendespite developed
Weilcome,
responded
pulmonary
because
pulmonary
to sulfamethoxazole
this
biopsy
the
chest
disease, on which, no radiographic
was
was
right upper lobe 2 months after transplantation, the precise cause of which was
edema BMT.
ity
rhagic clearly
patient obliter-
(BOOP)
Hodgkin retrospect,
ditional
neutropenia.
Two cases of pulmonary oped at 9 and 1 1 months
In 12 of the 21 cases,
demonstrated diagnostically significant findings not apparent on chest radiographs (Table). All radiographs included in this study were abnormal, except those the one patient with recurrent
case
and
each
fungab
of P carinii
virus
pneumonia,
pneumonia,
one
pneumonia
and
one
case
of a
October
1991
a. Figure
3.
CT scan
algorithm) cabized sions
cystic were
C.
Figure
2.
Images
of 49-year-old
developed fever and BMT. (a) Radiograph
man
who
cough 2 years after is abnormal, demon-
strating bilateral areas of scarring, particularly in the middle and lower lung zones. The radiographic findings, however, had not changed over the previous 3 months. (b) High-resolution CT scan (1.5-mm collimation with use of high-spatial-frequency reconstruction algorithm) obtained at level of aortic arch shows a bilateral ground-glass pattern. Mild parenchymal scarring can be seen in the posterior aspect of the right upper lobe. (c) High-resolution CT scan through the lung bases shows more extensive scarring and cylindrical bronchiectasis
but only
minimal
ground-glass
pattern.
On
the basis of the CT findings, bronchoalveolar lavage was performed in the right upper lobe and demonstrated the presence of P aeruginosa pneumonia.
cytotoxic
drug
of pulmonary
reaction,
and
two
cases
edema.
DISCUSSION The intrathoracic that occur following
complications allogeneic
are
a major
diverse
Volume
and
181
are
#{149} Number
1
cause
BMT of
areas
not
ground-glass
b.
(1.5-mm
collimation,
of 37-year-old in both
apparent
pattern
on
upper
lobes
the
radiograph.
on the radiograph
morbidity and mortality (4-10). Although chest radiography is performed routinely in these patients and often gives the first clue to the presence of intrathoracic complications, it has low sensitivity and specificity (3). In the present evaluation of 21 intrathoracic complications in 18 BMT recipients, chest CT demonstrated additional findings that were not apparent on radiographs in 57% of cases. CT was particularly useful in the case of recurrent Hodgkin disease. Radiography demonstrated no abnormality, but CT demonstrated mediastinab lymphadenopathy, which proved to be recurrent Hodgkin disease. Pneumonias complicate a significant number of transplantations (1,6) and may develop early ( < 100 days) and late ( > 100 days) after transplantation (5). In the present study, pneumonias
accounted
for
13 of the
standard
reconstruction
man with P carinii pneumonia
21
(arrows). The
and
These patient
shows iocystic lealso
had
a
CT scan.
distribution pattern was not specific and was found in occasional cases of infection and other noninfectious complications. Pulmonary edema is a recognized early complication of BMT (5,7). Often the diagnosis can be readily made. Pulmonary edema may, however, manifest with atypical clinical and radiologic findings; the diagnosis then requires open lung biopsy. Our study included two such cases; CT did not provide additional information in either case. The absence of any patients with cytomegabovirus pneumonia from this study is due to two factors. First, although cytomegabovirus pneumonia is reported to be a frequent respiratory complication of BMT (4,5), it is relatively uncommon at our institution. Second, the few cases that we have seen in BMT recipients demonstrated symptoms
the
classic constellation and signs (dyspnea,
of fever,
complications. CT provided useful additional information in seven of these cases, either by demonstrating early small lesions not apparent on radiographs or by demonstrating acute changes superimposed on chronic lung disease. Thus, CT may be particularly useful in a patient without definite new radiographic abnormalities in whom an acute pubmonary episode is suspected clinically. Pulmonary GVHD and BOOP are
bilateral infiltrates in the appropriate clinical setting (ie, 6-12 weeks after transplantation in cytomegalovirusseropositive patients who had acute GVHD). The diagnosis was therefore strongly suspected clinically, and, as the patients were extremely ill, rapid pathologic confirmation was obtained bronchoscopically without obtaining a prior chest CT scan. Patient selection probably also accounted, at least in part, for the high yield of CT find-
well-recognized
ings was
complications
in
long-term survivors of BMT (5,11,12). In the present study, the peribronchial and peripheral distribution of these abnormalities was not apparent on radiographs but was clearly demonstrated on CT scans. However, this
severe hypoxemia, on the radiograph)
not apparent performed
at radiography. in patients with
CT fever
and pulmonary symptoms but normal or questionable radiographic findings and before invasive procedures such as open lung biopsy. Although this point
was
not
Radiology
specifi#{149} 155
a. Figure
b. 4.
Images
of 22-year-old
man
with
severe
dyspnea
and
dry
cough
1 year
level of right upper lobe bronchus shows penbronchiai (arrows) and subpleural peripheral distribution at lung bases. Open lung biopsy demonstrated GVHD.
cabby addressed in this study, it has been shown that CT is useful in immunocompromised patients undergoing open lung biopsy (13,14). In this population, the object of the procedure is to sample areas of most severe involvement because these are most likely to be diagnostic (14). As CT is superior to radiography in determining both the distribution and the extent of active disease, it is more helpful in planning appropriate biopsy sites.
CT
is performed
almost
rou-
tineby before open lung biopsy at our institution. No specific attempt was made in this study to compare conventional with high-resolution CT. However, the ground-glass pattern present in patients with early pneumonia was better delineated on high-resolution CT scans. This is in keeping with the results of previous studies (15,16). Recently, Leung et al demonstrated that in patients with chronic diffuse infiltrative lung disease, a limited number of high-resolution CT scans can provide a diagnostic accuracy similar to that of complete conventional CT scanning (17). Obviously, if the examination is limited to a small number of high-resolution CT scans, focal parenchymab abnormalities and small nodules may be missed. Therefore, the optimal kind of examination, whether high-resolution CT or a combination of conventional and high-resolution CT, depends on the clinical situation.
156
#{149} Radiology
after
allogeneic
consolidation.
At our institution, the limited availability of CT scanner time also has an important effect on technique, because patients with intrathoracic complications following allogeneic BMT usually require CT within 24 hours of admission. Therefore, in these patients, we currently obtain high-resolution CT scans at 10- or 20-mm intervals through the chest, complemented by one or more images at bevels in which abnormalities are suspected on the chest radiograph. Only when assessing
for
possible
presence
of a tu-
mor do we perform complete conventional CT in these patients. In conclusion, although chest CT will probably not provide the definitive diagnosis in most intrathoracic complications of allogeneic BMT, it is superior to chest radiography in demonstrating the presence and extent of these abnormalities. CT should be performed before any invasive diagnostic procedure such as open lung biopsy
optimal
to guide
the
biopsy
site.
surgeon
BMT.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
to the
#{149}
15.
References 1.
2.
3.
Solberg CO, Meuwissen HJ, Needham RN, Good RA, Matsen JM. Infectious complications of bone marrow transplant patients. Br MedJ 1971; 1:18-23. Winston DJ, Gale RP, Meyer DV, Young LS, and the UCLA Bone Marrow Transplant Group. Infectious complications of human bone marrow transplantation. Medicine 1979; 58:1-31. Wise RHJr, Shin MS. Gockerman JP, Zornes SL, Rubin E, Nath PH. Pneumonia in bone marrow transplant patients. AJR 1984; 143:
(a) High-resolution
(b) Ten-millimeter-collimation
16.
17.
CT
scan
obtained
at
CT scan shows
Hamilton PJ, Pearson ADJ. Bone marrow transplantation and the lung. Thorax 1986; 41 :49’-502. Bombi JA, Cardesa A, Llebaria C, et al. Main autopsy findings in bone marrow transplant patients. Arch Pathol Lab Med 1987; 3:125-129. Dickout WJ, Chan CK, Hyland RH, et al. Prevention of acute pulmonary edema after bone marrow transplantation. Chest 1987; 92:303309. El-Khatib EE, Freeman CR, Rybka WB, Lehnert s, Podgorsak EM. The use of CT densitometry to predict lung toxicity in bone marrow transplant patient. mt j Radiat Oncol Biol Phys 1989; 16:85-94. Allen BT, Day DL, Dehner LP. CT demonstration of asymptomatic pulmonary emboli after bone marrow transplantation: case report. Pediatr Radiol 1987; 17:65-67. Allan BT, Patton D, Ramsey NKC, Day DL. Pulmonary fungal infections after bone marrow transplantation. Pediatr Radiol 1988; 18: 118-122 McLoud TC, Epler GR, Colby TV, Gaensler EA, Carrington CB. Bronchiolitis obliterans. Radiology 1986; 159:1-8. Muller NL, Staples CA, Miller RR. Bronchiolitis obliterans organizing pneumonia: CT feahires in 14 patients. AIR 1990; 154:983-987. Kuihman JE, Fishman EK, Meziane MA, Khouri NF, Zerhouni EA, Siegelman SS. CT diagnosis of opportunistic chest infections in the immunocompromised host with CT-pathologic correlation (abstr). Radiology 1986; 161(P):390. Miller RR, Nelems B, Muller NL, Evans KG, Ostrow DN. Lingular and right middle lobe biopsy in the assessment of diffuse lung disease. Ann Thorac Surg 1987; 44:269-273. Muller NL, Staples CA, Miller RR, Vedal 5, Thurlbeck WM, Ostrow DN. Disease activity in idiopathic pulmonary fibrosis: CT and pathologic correlation. Radiology 1987; 165: 731-734. Mathieson JR. MayoJR, Staples CA, Muller NL. Chronic diffuse infiltrative lung disease: comparison of diagnostic accuracy of CT and st radiography. Radiology 1989; 171:111Leung AN, Staples CA, Muller NL. Chronic diffuse infiltrative lung disease: comparison diagnostic accuracy ofhigh-resolution and conventional CT. AIR (in press).
of
707-714.
4.
Krowka MJ, Rosenow EC, Hoaglund HC. Pulmonary complications of bone marrow transplantation. Chest 1985; 87:237-246.
October
1991
