British Journal of Radiology (2004) 77, 724-727
© 2004 British Institute of Radiology
doi: 10.1259/bjr/70800575
Cytomegalovirus pneumonia after bone marrow transplantation: high resolution CT findings
E L Gasparetto, MD1,
S E Ono, MD1,
D Escuissato, MD1,
E Marchiori, MD1,
L Roldan, MD2,
H L Marques, MD2 and
R L Frare e Silva, MD2
Departments of 1 Diagnostic Radiology and 2 Internal Medicine, University of Paraná, Brazil
Correspondence: Emerson L Gasparetto, MD, Serviço de Radiologia Médica, Hospital de Clínicas da UFPR, Av General Carneiro 181, CEP: 80060900, Curitiba, Paraná, Brazil
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Abstract
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Cytomegalovirus (CMV) pneumonia is one of the most common pulmonary complications after bone marrow transplantation (BMT). We describe the high resolution CT (HRCT) findings of 13 patients with CMV pneumonia diagnosed after allogenic BMT. The study included 13 consecutive patients who developed CMV pneumonia after BMT and who had HRCT of the chest performed within 24 h of the onset of symptoms. HRCT scans were reviewed by two radiologists who assessed pattern and distribution of findings. There were nine male and four female patients, ranging from 9 years to 56 years of age (mean age 33 years). BMT was performed for treatment of chronic myelogenous leukaemia (54%), severe aplastic anaemia (23%), acute myelogenous leukaemia (15%) and Fanconi's anaemia (8%). The time elapsed until diagnosis ranged from +18 days to +405 days (median of 54 days, mean +81.6 days). The predominant patterns of abnormality on HRCT scans were ground-glass opacities (69%), small centrilobular nodules (69%) and air-space opacities (54%). The abnormalities were distributed in the central and peripheral zones of the lungs in six cases, only in the periphery in four cases, and only in the central zone in three cases. In all cases the lung lesions were bilateral, and asymmetry was observed in seven cases. The authors conclude that the most common HRCT findings in patients with CMV pneumonia after BMT consist of bilateral asymmetric ground-glass, air-space opacities and small centrilobular nodules.
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Introduction
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Bone marrow transplantation (BMT) is the treatment of choice for many haematological malignances and severe disorders of the haematopoietic and immune systems. A wide variety of pulmonary complications occur in BMT recipients and are a major cause of morbidity and death. These complications include infection, graft-versus-host disease (GVHD), drug-induced lung disease, transient pulmonary oedema, adult respiratory distress syndrome, pulmonary haemorrhage and recurrent malignancy [1, 2].
A significant proportion of pulmonary abnormalities seen in BMT patients are viral infections. The most commonly identified organism is cytomegalovirus (CMV), which may cause pneumonia in up to 50% of BMT recipients. Limited information is available, however, concerning the high resolution CT (HRCT) findings of CMV pneumonia in bone marrow transplant patients [1–6].
The aim of this study was to review the HRCT findings of 13 patients with CMV pneumonia diagnosed after allogenic BMT.
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Patients and methods
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The medical records of all patients who underwent BMT at the Hospital de Clínicas of the University of Paraná, Brazil from 1993 to 2002 were reviewed to identify patients with proven CMV pneumonia. At our BMT unit, all patients who have undergone BMT and have respiratory symptoms are tested for CMV, and all patients who are suspected of having pneumonia undergo HRCT. Only patients who had HRCT performed within 24 h after the beginning of symptoms, and no evidence of another superimposed pulmonary complication were included in the study. Seven patients with CMV pneumonia had GVHD at the time of diagnosis. They were included in the study after review of the HRCT findings showed similar findings as the remaining patients with CMV infection and no additional pulmonary abnormalities.
The diagnosis of CMV pneumonia was made through lung biopsy or clinical evidence of CMV pneumonia associated with positive laboratory studies polymerase chain reaction (PCR) of blood or bronchoalveolar lavage fluid and CMV antigenaemia assay) and evidence of lung lesions on HRCT scans [7, 8].
There were nine male (69%) and four female (31%) patients, with ages ranging from 9 years to 56 years of age (mean 33.3 years). The underlying disorders for which BMT was performed were chronic myelogenous leukaemia (n=7, 54%), severe aplastic anaemia (n=3, 23%), acute myelogenous leukaemia (n=2, 15%) and Fanconi's anaemia (n=1, 8%). All the patients underwent allogenic BMT. The CMV serostatus was positive in 77% of the donors and in 77% of the recipients before the BMT. The time elapsed between BMT and the diagnosis of CMV infection ranged from 18 days to 405 days (median of 54 days, averaging 81.6 days). One patient had the infection in the neutropenic phase, 11 (85%) during the post-engraftment period, and one patient had a "very late" CMV pneumonia 405 days after the BMT. The most common clinical presentations were fever (100%), dyspnoea (69%), and cough (15%). Severe GVHD was histologically proved in 7 cases (54%). The mortality rate was 62% (n=8).
The HRCT was performed at end-inspiration using 1 mm collimation at 10 mm intervals (Somaton ART; Siemens, Germany). Images were photographed at mediastinal (width, 400 H; level, 20 H) and lung (width, 1500 H; level, –700 H) window settings. Two radiologists analysed the HRCT scans and reached final decisions regarding the findings by consensus. The following HRCT findings were assessed: distribution of the lesions (central and/or peripheral, unilateral or bilateral, symmetrical or asymmetrical, and upper/middle/lower zones distribution), pattern of abnormality (ground-glass and air-space opacities, bronchial dilatation, bronchial wall thickening, tree-in-bud opacities, reticular opacities, large or small nodules, mosaic perfusion and vessel attenuation), lymph node enlargement, pleural effusions, as well as any other lung abnormalities. Criteria for these findings were those defined in the Fleischner Society's Glossary of Terms [9].
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Results
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All the patients had abnormal HRCT scans. The abnormalities included ground-glass opacities (n=9, 69%), small centrilobular nodules (n=9, 69%), air-space consolidations (n=7, 54%), reticular opacities (n=5, 38%), and large nodules (n=3, 23%). The areas of ground-glass and air-space opacities were multifocal. The centrilobular nodules were ill defined, ranging from 1 mm to 5 mm in diameter. The three patients who presented with large nodules had multiple lesions, ranging from 10 mm to 20 mm in diameter, distributed mainly in the periphery of the lower lobes. Pleural effusion was seen in three patients (23%), being bilateral in two. Most of the patients (92%) had mixed patterns, mainly the association of ground-glass opacities and small centrilobular nodules (n=3), and air-space opacities and small centrilobular nodules (n=2) (Figures 1–6
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Figure 1. 13-year-old female with chronic myelogenous leukaemia and cytomegalovirus pneumonia. High resolution CT at the level of the middle lobe shows diffuse ground-glass attenuation and a large irregular nodule at periphery of the middle lobe.
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Figure 2. 46-year-old male with chronic myelogenous leukaemia and cytomegalovirus pneumonia. High resolution CT at the level of the basal segments of the lower lobes demonstrates patchy ground-glass opacities, some of then with centrilobular distribution.
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Figure 3. 33-year-old male with chronic myelogenous leukaemia and cytomegalovirus pneumonia. High resolution CT at the level of the basal segments of the inferior lobes shows a reticular pattern with central predominance.
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Figure 4. 38-year-old male with chronic myelogenous leukaemia and cytomegalovirus pneumonia. High resolution CT at the level of (a) the carina and (b) the inferior pulmonary veins demonstrates foci of consolidation and patchy centrilobular nodular opacities with ground-glass halo.
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Figure 5. 45-year-old male with chronic myelogenous leukaemia and cytomegalovirus pneumonia. High resolution CT at the level of the lung base shows areas of ground-glass attenuation, with relative sparing of the periphery of the lungs.
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Figure 6. 13-year-old male with chronic myelogenous leukaemia and cytomegalovirus pneumonia. High resolution CT by the carina demonstrates ground-glass pattern associated with areas of consolidation and foci of lung with density nearly normal. Pneumomediastinum is also observed.
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The parenchymal abnormalities were distributed in both the central and peripheral zones of the lungs in six of 13 patients (46%), only in the periphery in four cases (31%), and only in the central zone in three cases (23%). The lower zone of the lungs was involved in all cases, the middle zone in 10 cases (77%), and the upper zone in 9 cases (69%). In all cases the lung lesions were bilateral, and asymmetry was observed in 7 cases (54%).
The HRCT findings in the 7 patients who had GVHD were similar to the remaining patients. The findings included ground-glass attenuation pattern (n=5), air-space opacities (n=5), small centrilobular nodules (n=5) and reticular opacities (n=1).
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Discussion
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BMT is a well-established form of treatment for various haematological disorders, particularly leukaemia, aplastic anaemia, and immunodeficiency states such as severe combined immunodeficiency syndrome. The major complications of BMT are related to the side effects of chemotherapy and radiation, immunosupression prior to or immediately after engraftment, and to the graft's immune response to the host [1, 2]. Pulmonary complications occur in 40–60% of BMT recipients and represent an important cause of morbidity and death. These complications are associated with the immunological status of the patients and occur in three phases. (1) Neutropenic phase: this phase is characterized by a period of severe neutropenia after the BMT. Respiratory complications are mainly bacterial and fungal infections. Other common complications during this period include diffuse alveolar haemorrhage, pulmonary oedema, and drug toxicity. (2) Early phase: this phase occurs up to 100 days after BMT, and during that time there is a gradual recovery of the neutrophil count and a reduction of immune impairment. The two most common pathogens to cause pulmonary complications during this phase are CMV and Pneumocystis carinii, which is declining since the introduction of routine prophylaxis. (3) Late phase: late complications are those occurring at least 100 days after BMT when the immune status has mostly been recovered. At this stage, the pulmonary complications observed are non-infective bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia (BOOP), and chronic GVHD [1–3]. In our study, 85% (n=11) of the cases of CMV pneumonia occurred in the early phase after BMT (median of 54 days, average of 81.6 days).
CMV infection occurs in up to 70% of BMT recipients, and approximately one-third develop CMV pneumonia [1]. Interstitial pneumonia in the allogeneic marrow recipient is the most common manifestation of CMV, occurring in the first 100 days after BMT, with a mortality rate ranging from 30% to 70% despite adequate treatment [7]. The major risk factor is pre-transplant seropositivity of the patient. Secondary factors include donor seropositivity, severe GVHD, unrelated or mismatched transplants, and delayed recovery of the CMV-specific cytotoxic T-cell response [7, 10]. The infection is caused by re-activation of the latent virus at a time of profound immunosupression or infusion of CMV-seropositive marrow or blood products into a CMV-seronegative recipient [3]. Concerning the risk factors related to CMV pneumonia after BMT, 77% of our recipient patients had CMV seropositivity pre BMT, 77% of the donor patients were also seropositive before the transplantation, and in seven patients (54%) severe GVHD was diagnosed. The mortality rate in our study was 68%.
Our study shows that the main patterns of abnormality on HRCT of patients with CMV pneumonia are ground-glass opacities, small centrilobular nodules and areas of consolidation. The abnormalities are usually bilateral and asymmetric in distribution. These findings are similar to those described in previous studies concerning this infection in immunocompromised patients. Franquet et al [6] reviewed the thin-section CT findings of 32 immunocompromised patients, including 25 cases post-BMT. The main patterns observed in this study were areas of ground-glass opacification (66%), multiple small nodules (59%) and areas of air-space consolidation (59%). In the study of Moon et al, 10 non-AIDS immunocompromised patients with CMV pneumonia are presented, and bilateral patchy areas of ground-glass opacity, seen in all patients, poorly-defined centrilobular small nodules (90%), and areas of consolidation (70%) were the predominant CT findings [4].
The HRCT findings observed in our study are different from those showed in AIDS patients. McGuinness et al correlated the CT and pathological aspects of 21 cases of AIDS patients with CMV pneumonia [11]. Nodules and masses were the most common parenchymal lesions (57%), followed by ground-glass attenuation (43%), dense consolidation (33%) and interstitial reticulation (28%). In most cases (n=12, 57%), the distribution of the parenchymal disease involved the upper, middle and lower lung zones equally. The lung bases were involved in all but two cases (90%).
Our study shows that CMV pneumonia is an infection that occurs mainly in the early phase after the BMT (30–100 days). The HRCT usually demonstrates bilateral and asymmetric distribution of a mixed pattern of ground-glass opacities, small centrilobular nodules and air-space consolidation.
Received for publication November 11, 2003.
Revision received March 22, 2004.
Accepted for publication May 18, 2004.
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References
|
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- Ettinger NA. Pulmonary considerations of organ transplantation. Part 2. Am Rev Respir Dis 1991;144:213–23.[Medline]
- Leung AN, Gosselin MV, Napper CH, Braun SG, Hu WW, Wong RM, et al. Pulmonary infections after bone marrow transplantation: clinical and radiographic findings. Radiology 1999;210:699–710.[Abstract/Free Full Text]
- Worthy SA, Flint JD, Müller NL. Pulmonary complications after bone marrow transplantation: high-resolution CT and pathologic findings. Radiographics 1997;17:1359–71.[Abstract]
- Kang EY, Patz EF Jr, Müller NL. Cytomegalovirus pneumonia in transplant patients: CT findings. J Comput Assist Tomogr 1996;20:295–9.[CrossRef][Medline]
- Moon JH, Kim EA, Lee KS, Kim TS, Jung KJ, Song JH, et al. Cytomegalovirus pneumonia: high-resolution CT findings in ten non-AIDS immunocompromised patients. Korean J Radiol 2000;1:73–8.[Medline]
- Franquet T, Lee KS, Muller NL. Thin-section CT findings in 32 immunocompromised patients with cytomegalovirus pneumonia who do not have AIDS. AJR Am J Roentgenol 2003;181:1059–63.[Abstract/Free Full Text]
- Ibrahim A, Gautier E, Roittmann S, Bourhis JH, Fajac A, Charnoz I, et al. Should cytomegalovirus be tested for in both blood and bronchoalveolar lavage fluid of patients at a high risk of CMV pneumonia after bone marrow transplantation? Br J Haematol 1997;98:222–7.[CrossRef][Medline]
- Machida U, Kami M, Kanda Y, Mori S, Ohashi K, Tanikawa S, et al. Comparison of the antigenemia assay and screening bronchoscopy for detection of cytomegalovirus infection after bone marrow transplantation. Bone Marrow Transplant 1999;24:1153–4.[CrossRef][Medline]
- Austin JH, Muller NL, Friedman PJ, Hansell DM, Naidich DP, Remy-Jardin M, et al. Glossary of terms for CT of the lung: recommendations of the nomenclature committee of the Fleischner Society. Radiology 1996;200:327–30.[Free Full Text]
- Medeiros CR, Moreira VA, Pasquini R. Cytomegalovirus as a cause of very late interstitial pneumonia after bone marrow transplantation. Bone Marrow Transplant 2000;26:443–4.[CrossRef][Medline]
- McGuinness G, Scholes JV, Garay SM, Leitman BS, McCauley DI, Naidich DP. Cytomegalovirus pneumonitis: spectrum of parenchymal CT findings with pathologic correlation in 21 AIDS patients. Radiology 1994;192:451–9.[Abstract/Free Full Text]
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Abstract
Introduction
