Page 1280 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 94: Hematopoietic Stem Cell Transplantation and Graft-Versus-Host Disease 887

obliterans syndrome [BOS] and bronchiolitis obliterans organizing infectious organism. Because the pathogenesis of DAH is thought to
pneumonia [BOOP]). Pulmonary edema during the peritransplant have a significant inflammatory component, patients are treated with
period is often related to administration of large volumes of intravascu- corticosteroids. Studies using other interventions including plasma
lar fluid, chemotherapy-induced cardiac dysfunction, or sepsis-induced exchange, plasmapheresis, and administration of fresh frozen plasma
acute respiratory distress syndrome. Idiopathic pneumonia syndrome have failed to show definitive evidence supporting their use. Several
can occur at any time following transplant. 6 case reports have shown efficacy of recombinant factor VIIa for the
■ IDIOPATHIC PNEUMONIA SYNDROME treatment of DAH in allogeneic HSCT recipients. The majority of
53-55
patients will require mechanical ventilatory support for respiratory
Definition and Incidence: Idiopathic pneumonia syndrome (IPS) was failure and these patients are at risk for subsequent infectious com-
plications. The reported mortality rate of DAH in HSCT is approxi-
originally defined by a National Institutes of Health workshop in 1993 as mately 80% with a range between 50% and 100%. However, despite
diffuse lung injury occurring after HSCT for which an infectious etiol- the high mortality rate, long-term survivors can recover with normal
ogy is not identified. The overall incidence of IPS is 10% with a median respiratory function. 48
47
time of onset between 20 and 90 days after HSCT. 48,49 Risk factors for the
leukemia, pretransplant chemotherapy, total body irradiation, GVHD, ■ PERIENGRAFTMENT RESPIRATORY DISTRESS SYNDROME
development of IPS include old age, transplant for malignancy other than
and positive donor CMV serology. IPS is rare in autologous HSCT. Incidence: The term engraftment syndrome (ES) is used to describe
48
a clinical condition that includes fever, rash, and noncardiogenic pul-
Diagnosis and Management: IPS is a diagnosis of exclusion made only monary edema which occurs during early neutrophil recovery in the
after infection and other causes of lung injury are ruled out follow- absence of infection. Periengraftment respiratory distress syndrome
ing a thorough evaluation. Diagnostic criteria include symptoms and (PERDS) refers to the pulmonary component of ES. The incidence
signs of pneumonia (dyspnea, fever, and nonproductive cough), diffuse of PERDS varies depending on the definition used to describe ES. It is
radiographic infiltrates, increased alveolar to arterial oxygen gradient, reported at about 5% in autologous recipients where it is well described.
56
and absence of active lower respiratory tract infection on bronchoal- PERDS is also reported as a common occurrence in cord blood
veolar lavage or lung biopsy. Lung biopsy specimens may show diffuse transplantation. One study reported an incidence of 78% in patients
alveolar damage or interstitial pneumonitis. 48,49 The occurrence of receiving a single cord blood transplant. Another study using a more
57
IPS after both allogeneic and autologous HSCT implies that shared strict definition reported an incidence of 31% after double-unit cord
conditioning-related toxicities, rather than immune-mediated injury blood transplantation. The syndrome generally occurs within 5 days of
58
may be involved. However, the association of IPS with acute GVHD neutrophil engraftment. 56,59
after allogeneic HSCT suggests that alloreactive T-cell injury may be
contributory. 48-50 Management of IPS is primarily supportive care with Diagnosis and Management: The diagnostic criteria of PERDS include
prevention and treatment of superimposed infection. Large studies fever and pulmonary injury manifested by hypoxemia and/or pulmo-
have failed to demonstrate improvement in outcome with the use of nary infiltrates in the absence of cardiac dysfunction and infection.
corticosteroids. Antitumor necrosis factor (TNF) agents such as Dyspnea is present in all cases although pulmonary infiltrates may not
48
etanercept are being studied in clinical trials. Although pneumonitis be present at the onset of symptoms. Fever is present in over half of the
resolves in about 31% of patients with IPS, complications from infec- patients. BAL may show neutrophilic inflammation. Transbronchial
tion, pneumothorax, pneumomediastinum, subcutaneous emphysema, lung biopsy is usually contraindicated in the setting of thrombocyto-
pulmonary fibrosis, and autoimmune polyserositis can complicate the penia. Lung biopsies may show diffuse alveolar damage. The patho-
picture. The overall mortality of IPS is about 70% to 80% but may physiology behind ES as well as PERDS is multifactorial and may
48
exceed 95% for those who require mechanical ventilation. 48,49 involve cellular interaction of T cells, monocytes and other effector cells,
■ DIFFUSE ALVEOLAR HEMORRHAGE complement activation, and proinflammatory cytokine production and
Treatment with corticosteroids is usually effective, leading
release.
48,49,56
Incidence: DAH is a life-threatening pulmonary complication after to rapid clinical improvement. Admission to the ICU is less common in
HSCT with nonspecific clinical and radiologic features. The reported PERDS than it is in DAH or BOS, with only about one-third of patients
requiring ICU admission and mechanical ventilation. The mortality is
frequency of DAH varies from 1% to up to 21% for both autologous 49
and allogeneic HSCT recipients. 48,51 Risk factors for DAH include reported to be about 25%.
chemotherapy, myeloablative conditioning, total body irradiation, tho- ■ BRONCHIOLITIS OBLITERANS SYNDROME
many of the same as for IPS: older age, high intensity of pretransplant
racic irradiation, allogeneic donor source, and severe acute GVHD. 48-52 Incidence: Bronchiolitis obliterans syndrome (BOS) is characterized by
The etiology and pathogenesis of DAH after HSCT are not well defined the presence of fixed airflow obstruction with the histologic presence
but as with many complications of transplant tissue injury, inflammation of bronchiolar fibrosis with luminal narrowing and fibrosis. BOS is a
and cytokine release have all been implicated as causative factors. The late onset (typically >6 months), uncommon, noninfectious pulmonary
52
onset of DAH is usually within the first 30 days after HSCT but cases complication associated with chronic GVHD after allogeneic HSCT. Risk
after the first month can be observed. factors include many of the same as those for GVHD as well as prior
abnormalities of pulmonary function. Due to the delays in diagnosis, the
Diagnosis and Management: DAH is characterized by progressive true prevalence is not known but is estimated to range from approximately
dyspnea, fever, nonproductive cough, and hypoxemia with diffuse 2% to 3% among all allogeneic HSCT recipients to 6% of those patients
alveolar and interstitial infiltrates on chest x-ray and ground-glass who develop chronic GVHD. However, studies using more relaxed crite-
60
infiltrates or consolidation on computed tomography (CT) scans ria for diagnosis have suggested that the prevalence may be higher.
generally involving the middle and lower lung fields. Abnormal pul-
monary physiology is observed with increased alveolar-to-arterial Diagnosis and Management: Airflow obstruction is the hallmark of
oxygen gradient and a restrictive ventilatory defect. A BAL shows BOS. The NIH proposed scoring system which is now being utilized
progressively bloodier return from three separate subsegmental bron- has been helpful in establishing pulmonary function testing criteria
chi or the presence of 20% or more hemosiderin-laden macrophages, which demonstrate an obstructive pattern—FEV <75% of pre-
1
or the presence of blood in at least 30% of the alveolar surfaces of dicted, FEV /FVC <0.7 and air trapping, residual volume of air (RV
1
lung tissue. The diagnosis of DAH is retrospective as it can only >120%). FEV is the most sensitive marker of emerging obstructive
51
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1
be made after culture results from the BAL return negative for an disease and severity of BOS. The onset of BOS varies from 3 months

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