Page 1896 - Hematology_ Basic Principles and Practice ( PDFDrive )

1678 Part X Transplantation

Infectious Causes of Interstitial Pneumonitis combination with corticosteroids in a recent, though small, multi-
center trial. 28,29
Infections are the most common cause of interstitial pneumonitis in
HCT recipients. CMV and Aspergillus are the most common infec- Diffuse Alveolar Hemorrhage
tions associated with interstitial pneumonitis and have been discussed Alveolar hemorrhage is a clinical syndrome of acute onset of pulmo-
earlier. Other important, though relatively uncommon infections to nary infiltrates and hypoxemia with a progressively bloodier BAL on
30
consider are Pneumocystis jirovecii, RSV and similar respiratory bronchoscopy. Alveolar hemorrhage arising from noninfectious
viruses. causes has been called diffuse alveolar hemorrhage, but it is often
Pneumonitis caused by Pneumocystis has a typical bilateral distri- difficult to distinguish it from infection-associated pulmonary hem-
30
bution with a ‘butterfly’ pattern on chest radiograph and prominent orrhage, especially in the early posttransplant period. The reported
hypoxemia, and rarely causes pleural effusions. The previously incidence of diffuse alveolar hemorrhage ranges from 2% to 5% in
reported 5% to 15% risk of Pneumocystis pneumonia has been autologous and 5% to 10% in allogeneic HCT recipients. Its patho-
largely eliminated by routine use of prophylaxis with TMP-SMX genesis is not known, but it most likely develops as result of a complex
(first choice), dapsone, atovaquone, or inhaled pentamidine. Pro- interaction of a variety of factors, including alveolar injury from
phylaxis with TMP-SMX virtually eliminates Pneumocystis pneumo- radiation and chemotherapy, inflammatory damage caused by neu-
nia from the differential diagnosis, but only if patient compliance trophils and cytokines, and underlying infections. Older age at
with therapy is certain. Diagnosis requires cytologic evaluation of transplant, use of an allogeneic donor source, and GVHD are risk
silver-stained preparations of BAL cells or sputum, although trans- factors for this syndrome. The risk is similar with NMA and myeloab-
31
bronchial lung biopsy may slightly increase the diagnostic yield of a lative conditioning regimens. Onset typically occurs within the first
bronchoscopic examination. Pneumocystis pneumonia is effectively 3 months of transplantation with dyspnea, hypoxia, and cough,
treated with high dose TMP-SMX or parenteral pentamidine. Pro- although late-onset alveolar hemorrhage is also possible. Hemoptysis
phylaxis against Pneumocystis pneumonia should be continued is usually absent and bronchoscopy with BAL is required to confirm
through the period of immunosuppression (6 months to 1 year the diagnosis and to exclude infectious etiologies. This syndrome is
posttransplantation) and for the duration of any therapy for chronic very serious and the majority of patients develop respiratory failure
GVHD. with mortality rates of more than 70%. Hemorrhage occurring in the
RSV is a potentially fatal cause of interstitial pneumonitis and periengraftment period is associated with a better outcome compared
typically occurs in the fall and winter months. RSV should be sus- with later-onset hemorrhage. Treatment includes correction of any
pected if the patient presents a history of rhinorrhea and if RSV has coagulopathy and aggressive ventilatory support. High-dose cortico-
been frequently recognized in the community or in the hospital. steroids have been used for its management, but their efficacy has not
Diagnosis can be made by rapid antigen or PCR testing on nasal been clearly proven. Small case series have reported the successful use
washings or BAL specimens. Because of the possibility of horizontal of recombinant factor VIIa and aminocaproic acid, but their efficacy
transmission, patients with RSV should be isolated. Inhaled and needs to be confirmed in clinical trials. Cytokine antagonists (e.g.,
sometimes oral ribavarin is used for treatment of RSV-associated etanercept) might have a therapeutic role that is being investigated
pneumonia. Other community acquired viruses, such as parainflu- in clinical trials.
enza or influenza can also cause interstitial pneumonitis in the
transplant recipient. Their presentation is clinically indistinguishable
from RSV though parainfluenza pneumonitis is not seasonal and may LATE NONINFECTIOUS COMPLICATIONS
be seen year round. Yearly influenza vaccination for HCT recipients
and especially their household contacts may be effective in reducing Improvements in transplantation techniques and supportive care have
risks of this infection. led to an increasing number of long-term HCT survivors. Among
HCT recipients who remain disease-free through 2–5 years post-
transplantation, the probability of survival over the following 10–20
Noninfectious Causes of Interstitial Pneumonitis years is more than 80%. 32,33 These survivors remain at risk for late
transplant associated complications, which can include specific organ
Idiopathic Interstitial Pneumonitis dysfunction, second cancers, infections because of ongoing immuno-
deficiency, functional impairments, and compromise in the quality
34
Idiopathic interstitial pneumonitis is a diagnosis of exclusion of life (QOL; Table 109.5). Guidelines for screening and prevention
based on typical findings and ruling out infectious causes. Its of late effects in HCT survivors have been published. 4,35 In addition,
timing is somewhat earlier than other causes of interstitial pneu- following general population guidelines for screening and prevention
monitis, typically occurring within the first 2–7 weeks after HCT. of cancers and chronic diseases and promoting a generally healthy
The recognized risk factors for idiopathic interstitial pneumonitis lifestyle is recommended for all HCT survivors.
include older age at transplant, extensive pretransplant chemo-
therapy, high-dose cyclophosphamide, TBI (higher total dose and
dose rate), blood transfusions, administration of methotrexate and Organ-Specific Late Effects
GVHD. 27
The observation that idiopathic interstitial pneumonitis is as A multitude of pre-, peri-, and post-HCT factors determine a
frequent among syngeneic as among allogeneic recipients and has patient’s overall risk for developing specific late complications.
an equally high incidence in T-cell depleted grafts, suggests that Risk factors include age at the time of HCT, gender, and lifestyle
immunosuppression is less of a risk factor for idiopathic interstitial factors such as tobacco and alcohol use. In addition, patients may
pneumonitis than it is for infectious interstitial pneumonitis. Clini- have preexisting comorbidities such as chronic renal insufficiency
cal observations support a toxic cause for idiopathic interstitial or cardiovascular disease that can be exacerbated by chemotherapy,
pneumonitis, and radiation-induced lung damage appears to be the radiation, and other medications they receive to treat their malig-
major contributor, especially the use of high-dose TBI. Effective nancy and during HCT. Exposure to chemotherapy and radiation
therapy has not been established, although high-dose corticosteroids as part of initial treatment of underlying hematologic disorder
are often administered. Inflammatory cytokines, including interleu- or as part of the conditioning regimen given before HCT also
kin (IL)-1 and TNF-α, have been implicated in lung injury. Etan- can contribute to organ-specific complications. Allogeneic HCT
ercept, a TNF-α binding protein has been reported to improve lung recipients who develop chronic GVHD may require long-term
function in patients with idiopathic interstitial pneumonitis, par- treatment with glucocorticoids, calcineurin inhibitors (e.g., cyclo-
ticularly if administered before the need for mechanic ventilation. sporine or tacrolimus), or other immunosuppressive agents and can
Its use was not confirmed to be better than placebo when used in be prone to developing medication-related side effects, infections