Page 1680 - Hematology_ Basic Principles and Practice ( PDFDrive )

1498 Part VIII Comprehensive Care of Patients with Hematologic Malignancies

recommendations, and screening for dyslipidemia. Joint recommen- obliterans requires the following: (1) absence of active infection, (2)
dations for monitoring long-term survivors of HCT by the European decreased FEV 1 (<75% of predicted value), (3) evidence of airway
Group for Blood and Marrow Transplantation (EBMT)/Center for obstruction with a ratio of FEV 1 to FVC of less than 0.7, (4) elevated
International Blood and Marrow Transplant Research CIBMTR)/ RV of air (>120% of predicted normal), or (5) an expiratory chest
American Society for Blood and Marrow Transplantation (ASBMT) computed tomographic (CT) scan or lung biopsy results that reveals
suggest that at a minimum, cholesterol and high-density lipoprotein- air trapping or bronchiectasis. Recommended therapy includes high-
cholesterol (HDL-C) should be checked at least every 5 years for men dose systemic steroids for a protracted course, with or without the
starting by age 35 years and women starting at 45 years of age. It is addition of other immunosuppressants. Leukotriene inhibitors have
suggested that screening for dyslipidemia should start at 20 years of emerged as a potential therapy because of the elevated levels of leu-
age for smokers, patients with diabetes, or patients with a family kotrienes implicated in bronchiolitis obliterans.
history of heart disease. Abnormalities (total cholesterol >200 mg/dL The COG LTFU guidelines recommend monitoring for pulmo-
or HDL-C <40 mg/dL) should be followed up with a full fasting nary dysfunction in childhood cancer survivors that includes assess-
lipoprotein profile. 83 ment of symptoms such as chronic cough or dyspnea on annual
follow-up. Risks of smoking and exposure to second-hand smoke
should be discussed with all patients. The best approach to chronic
PULMONARY EFFECTS pulmonary toxicity of anticancer therapy is preventive and includes
respecting cumulative dosage restrictions of bleomycin and alkylators,
Compromise of pulmonary function among survivors of hematologic limiting radiation dosage and port sizes, and avoidance of primary or
malignancies has been reported after conventional therapy. 13,14,84–86 second-hand smoke. Pulmonary function tests are recommended as
Impairments evident by pulmonary function testing include reduc- a baseline upon entry into long-term follow-up for patients at risk,
tions in total lung capacity (TLC), forced vital capacity (FVC), forced repeated as clinically indicated in symptomatic patients and in those
expiratory volume in the first second of expiration (FEV 1), and gas with subclinical abnormalities identified on screening evaluation.
transfer (diffusing capacity of lung for carbon monoxide [DLCO]), Repeat evaluation should also be considered for at-risk patients before
suggesting obstructive and restrictive defects. Risk factors include general anesthesia. Influenza and pneumococcal vaccines are encour-
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exposure to certain chemotherapeutic agents (particularly bleomycin), aged in survivors at risk for pulmonary compromise. Joint recom-
radiation to the chest, underlying lung disease, female sex, and a mendations for monitoring long-term survivors of HCT by the
younger age at exposure to the pulmonary-toxic therapeutic agents. EBMT/CIBMTR/ASBMT suggest: (1) routine clinical assessment at
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In a recent study, Armenian et al demonstrated an elevated risk of 6 months, 1 year, and annually thereafter, (2) institution of active
pulmonary compromise among childhood cancer survivors when smoking cessation programs, and (3) pulmonary function tests and
compared with healthy controls and identified populations at focused radiologic assessment at 1 year after allogeneic HCT for
increased risk for pulmonary toxicity. Compared with healthy con- patients with signs or symptoms of lung compromise or earlier as
trols, childhood cancer survivors were 6.5-fold more likely to develop clinically indicated. Annual testing is recommended thereafter for
restrictive defects and 5.2-fold more likely to develop diffusion patients with recognized defects or appropriate clinical circumstances.
abnormalities. Among childhood cancer survivors, higher radiation For autologous HCT recipients, pulmonary function testing should
dose (>20 Gy) and younger age at exposure (<16 years) was associ- be performed for those with known deficits before HCT or with
ated with restrictive disease. Female sex and higher chest radiation those exposed to radiation or other pulmonary toxic agents during
dose were associated with diffusion abnormalities. Importantly, over or after transplantation. Chest radiographic studies are indicated
a period of 5 years, diffusion capacity declined among females and based on symptoms or abnormal pulmonary function test results. 83
those exposed to high doses of chest radiation.
Pulmonary complications, both infectious and noninfectious, are
common after HCT. Multiple factors are thought to contribute to ENDOCRINOLOGIC EFFECTS
pulmonary complications, including the type and duration of immu-
nological defects produced by the underlying disease and treatment, Thyroid
the development of GVHD, and the conditioning regimens employed.
These complications are classified as early or late, depending on Patients with hematologic malignancies treated with cranial, cranio-
whether they occur before or after 100 days from transplantation. spinal, or mantle irradiation are at increased risk for thyroid compli-
Early noninfectious pulmonary complications typically include pul- cations. Among survivors of HL, and to a lesser extent leukemia,
monary edema, upper airway complications, diffuse alveolar hemor- abnormalities of the thyroid gland, including hypothyroidism,
rhage, and pleural effusion. Bronchiolitis obliterans, venoocclusive hyperthyroidism, and thyroid neoplasms, have been reported to
disease, and secondary malignancies occur late after HCT. Idiopathic occur at rates significantly higher than those found in the general
pneumonia syndrome, GVHD, and radiation-induced lung injury population. 73–75 Hypothyroidism is the most common nonmalignant
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can occur in early or late periods after HCT (reviewed in Khurshid late effect involving the thyroid gland. After exposure to radiation
and Anderson). 88 at doses above 15 Gy, laboratory evidence of primary hypothyroidism
The following pulmonary function tests are noted to decline after is evident in 40% to 90% of patients with HL and NHL 91–93 ; risk
HCT: FEV 1 /FVC, forced mid-expiratory flow, TLC, DLCO, residual increases with radiation dose. 94
volume (RV), functional residual capacity, and RV/TLC. Older age In an analysis of 1791 5-year survivors of pediatric HL (median
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at the time of allogeneic HCT is associated with lower FEV 1 /FVC age at follow-up: 30 years), Sklar et al reported the occurrence of
and DLCO, and higher RV/TLC. Bronchiolitis obliterans syndrome at least one thyroid abnormality in 34% of subjects. The risk for
is a progressive, insidious lung disease occurring after allogeneic HCT hypothyroidism was increased 17-fold compared with sibling con-
and results in progressive circumferential fibrosis and ultimate cica- trols; increasing dose of radiation, older age at diagnosis of HL, and
trization of the small terminal airways, manifesting as new fixed female sex were identified to be significant independent predictors of
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airflow obstruction (reviewed in Williams et al). Bronchiolitis increased risk. The actuarial risk for hypothyroidism for subjects
obliterans has been shown to have a strong correlation with chronic treated with 45 Gy or more was 50% at 20 years after diagnosis of
GVHD and has been reported in up to 6% of HCT recipients. Most HL. Hyperthyroidism was reported to occur in only 5%. In a seminal
patients present when the degree of airflow is severe, causing signifi- study of 1677 patients with HL treated at Stanford University
cant dyspnea on exertion and a persistent nonproductive cough. Lung Hospital between 1961 and 1989 with irradiation involving the
biopsy findings demonstrating damage to the bronchiolar epithelium, thyroid (mean age at diagnosis: 28 years; mean duration of follow-up:
obliteration of bronchiolar lumens, inflammation between the epi- 9.9 years), the actuarial risk for developing thyroid disease was 52%
thelium and the smooth muscle, and pulmonary fibrosis are charac- at 20 years and 67% at 26 years after treatment. In this population,
teristic. The National Institutes of Health definition of bronchiolitis the actuarial risk for developing overt or subclinical hypothyroidism