NCI office of Cancer Survivorship
LiveStrong™ Foundation
National Marrow Donor Program
National Bone Marrow Transplant Link
HSCT survivors are faced with a significantly increased risk for chronic health conditions and premature death, even 10–15 years from their transplant procedure. The Bone Marrow Transplant Survivor Study (BMTSS) followed patients who survived at least 2 years post-HSCT and showed that the conditional survival probability at 15 years after allogeneic HSCT was 80 %, with mortality rates twice that of the general population after 15 years. For autologous HSCT recipients, the mortality rate is also higher for the first 10 years of survivorship before approaching that of the general population. Careful health surveillance, healthy lifestyle choices, and prompt management of medical conditions are essential to reduce nonrelapse mortality and improve quality of life. An international working group led by the NMDP recently updated the screening and preventive practice guidelines for patients who have undergone HSCT (see Table 34.2). The recommendations that follow will be focused on survivors who are alive more than 1 year post-HSCT.
Table 34.2
Recommended screening and preventive practices for post-HSCT patients. (Adapted from Majhail et al. 2012)
Recommended screening and prevention | Six months | One year | Annually |
|---|---|---|---|
Liver | |||
Liver function testing | All | All | As indicated |
Serum ferritin if patient received RBC transfusions | As indicated | As indicated | |
Respiratory | |||
Clinical pulmonary assessment | All | All | All |
Smoking tobacco avoidance | All | All | All |
Pulmonary function testing | cGVHD as indicated | Allo only | As indicated |
Chest radiography | As Indicated | As Indicated | As indicated |
Musculoskeletal | |||
Bone density testing (women, allo transplant, and patients with prolonged corticosteroid or calcineurin inhibitor use) | All | As indicated | |
Screen for corticosteroid-induced muscle weakness | cGvHD* | cGvHD* | cGvHD* |
Physical therapy consultation as indicated | cGvHD* | cGvHD* | cGvHD* |
Treatment of osteopenia with bisphosphonates | Those at risk | Those at risk | |
Kidney | |||
Blood pressure screening | All | All | All |
Urine protein screening | All | All | As indicated |
BUN/creatinine testing | All | All | All |
Nervous system | |||
Neurological clinical evaluation | All | As indicated | |
Endocrine | |||
Thyroid function testing | All | All | |
Growth velocity in children | All | All | |
Gonadal function assessment (prepubertal boys and girls) | All | All | All |
Gonadal function assessment (postpubertal women) | All | All | |
Vascular | |||
Cardiovascular risk factor assessment | All | All | |
Fasting lipid profile and blood glucose | All | All | |
Immune system | |||
Encapsulated organism prophylaxis | cGvHD* | cGvHD* | cGvHD* |
PCP prophylaxis | All | cGvHD* | cGvHD* |
CMV testing | cGvHD* | cGvHD* | As indicated |
Consider antifungal prophylaxis | cGvHD* | cGvHD* | cGvHD* |
Prophylaxis for VZV for those at risk | All | All | cGvHD* |
Endocarditis prophylaxis with dental procedures—AHA guidelines | All | All | All |
Immunizations—see Chap. 13 | All | All | All |
Second cancers | |||
Second cancer vigilance counseling | All | All | |
Breast/skin/testes self-exam | All | All | |
Clinical screening for second cancers | All | All | |
Pap smear, mammogram for women over the age of 40 (see text) | All | All | |
Psychosocial | |||
Psychosocial/QOL clinical assessment | All | All | All |
Mental health counseling for recognized psychosocial problems | As Indicated | As Indicated | As indicated |
Sexual function assessment | All | All | All |
Oral complications | |||
Dental assessment, intraoral malignancy assessment | All | All | All |
Ocular | |||
Ocular clinical symptom evaluation | All | All | All |
Ophthalmologic exam of visual acuity and fundus | All | As indicated |
34.1 Infection (See also Chaps. 10 and 17)
The risk of serious infection persists in HSCT recipients months to years after their procedure. Laboratory evidence of immune recovery generally occurs at 12 months for autologous patients but may be delayed in allogeneic recipients.
1.
Risk factors for late infection
a.
The presence of chronic graft versus host disease (cGVHD)
b.
Ongoing immunosuppressive therapy (IST)
c.
Cord blood, human leukocyte antigen (HLA) mismatched or T cell depleted graft
d.
The presence of relapsed disease
2.
Surveillance
a.
CBC at least annually
b.
Immune reconstitution assessment
i.
BMT CTN recommends post-allogeneic HSCT monitoring of T, NK, and B cell subsets (CD3, CD4, CD8, CD45RA/R0, CD56, CD16, CD19, CD20) and quantitative immunoglobulins at various milestones post-HSCT
c.
Cytomegalovirus (CMV) PCR based on risk factors including the intensity of IST regimen, the presence of cGVHD, post-HSCT maintenance therapy , etc.
3.
Interventions
a.
Antimicrobial prophylaxis (see also Chap. 10)
i.
Encapsulated bacteria prophylaxis for HSCT recipients who require extended IST; consideration should be given for those patients who are surgically/functionally asplenic.
ii.
Pneumocystis jiroveci pneumonia prophylaxis for the first 6 months post-autologous HSCT; continue for the duration of IST in allogeneic HSCT recipients.
iii.
Varicella zoster virus prophylaxis should continue for at least 1 year post-HSCT, longer in those patients who require prolonged IST.
iv.
Fungal prophylaxis is indicated for high-risk patients, specifically those with cGVHD requiring prolonged IST.
34.2 Cardiovascular (See also Chap. 23)
HSCT survivors are twice as likely as the general population to die from cardiac conditions. Reduced carotid artery distensibility has been demonstrated in a cohort of pediatric HSCT survivors (see also Chap. 23). Precocious coronary arteriosclerosis develops when the radiation field encompasses the heart. Conduction system disturbances, valve defects, or restrictive cardiomyopathy are additional late effects.
1.
Risk factors
a.
Cumulative anthracycline dose > 550/m2 daunorubicin equivalent
b.
Thoracic radiotherapy with heart in the radiation field, either before or after HSCT
c.
Iron overload associated with multiple transfusions, especially those patients with iron stores documented by cardiac magnetic resonance imaging (MRI)
d.
Metabolic syndrome
i.
A constellation of hypertension, insulin resistance, abdominal obesity, elevated triglycerides, reduced high-density lipoprotein (HDL) ➔ three of these five signs constitutes metabolic syndrome
ii.
Patients with metabolic syndrome have a 2–3 times higher risk of developing cardiovascular disease
iii.
Prevalence in HSCT survivors is 2 –3 times that of the general population
e.
Family history of cardiovascular disease
2.
Surveillance
a.
Screening for hypertension and cardiovascular risk annually
b.
Fasting lipid panel annually
c.
Electrocardiogram (ECG) and/or echocardiogram as clinically indicated
3.
Interventions
a.
Early intervention for identified risk factors (i.e., hypertension, dyslipidemia, etc.)
b.
Encourage healthy lifestyle choices including cardiac prudent diet, exercise, and smoking cessation
d.
Cardiology referral and evaluation as indicated
34.3 Pulmonary (also see Chap. 22)
Serious pulmonary complications generally develop during the first few weeks or months post-HSCT. However, pulmonary function can become compromised in long-term survivors as a consequence of late infection, obstructive, or restrictive disease .
1.
Risk factors
a.
cGVHD
b.
Immunosuppressive medications
c.
CMV disease and other infections
d.
Conditioning regimens including busulfan, carmustine, or total body radiation
e.
Pre-HSCT pulmonary dysfunction
f.
Older age
2.
Surveillance
a.
History and physical exam, including pulse oximetry.
b.
Pulmonary function testing (PFT) for allogeneic recipients at 1 year. However, as early presentation of bronchiolitis obliterans is asymptomatic and prognosis is poor for symptomatic disease, consider PFT monitoring as early as 3 months post-HSCT.
i.
More frequent PFT monitoring (every 3–6 months) may be indicated in patients with cGVHD, identified dysfunction, or new clinical symptoms of pulmonary dysfunction
c.
Appropriate imaging for symptomatic patients (CXR, high-resolution CT chest without contrast with expiratory views)
3.
Prevention and intervention
a.
Annual inactivated influenza vaccination for patients and close contacts
b.
Smoking cessation
c.
Education of patient and family on infection control measures to reduce exposure to community respiratory viral infections
d.
Prompt treatment of respiratory infections
34.4 Neurologic
1.
Cognitive dysfunction (see also Chap. 25)
Pediatric HSCT survivors suffer the greatest burden of neurologic effects post-HSCT. Adult HSCT patients can be plagued by cognitive dysfunction. However, the majority recover normal function by 1 year.
a.
Risk factors
i.
Patient age
ii.
Unrelated donor > matched sibling > autologous
iii.
GVHD, calcineurin inhibitors (CNIs)
iv.
Prior cranial radiation or intrathecal therapy
v.
Possible genetic predisposition (E4 allele of apoliprotein)
vi.
Preexisting cognitive deficits
b.
Surveillance and diagnosis
i.
Annual neurologic exam
Careful history from patient and family of intellectual, social, and physical functioning
ii.
Serum electrolytes, renal and liver function tests
iii.
MRI of brain if indicated
iv.
Referral for neurologic consultation and neuropsychological testing as indicated
c.
Interventions
i.
Treatment is individualized, based on age, degree of cognitive disruption, and presumed etiology
ii.
Research suggests physical exercise improves cognitive function
2.
Peripheral neuropathy
Ten to twenty percent of patients treated for a malignant disease develop peripheral neuropathy which may impair mobility, increase fall risk, and may require chronic narcotic analgesia. Neuropathy symptoms may gradually improve.
a.
Risk factors
i.
History of treatment with neurotoxic chemotherapeutic agents (vinca alkyloids, platinum compounds, bortezomib, thalidomide, taxanes)
ii.
CNIs
iii.
Older age
iv.
Diabetes mellitus and liver disease can exacerbate preexisting symptoms
b.
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Interventions
i.
Gamma aminobutyric acid for painful neuropathy
Gabapentin (Neurontin®) beginning at 100–300 mg po qhs, increasing dose to 900–3600 mg daily in dose increments of 50–100 % every 3 days. Slower titration recommended for elderly or medically frail patients. Dose adjust for renal insufficiency.
Pregabalin (Lyrica®) 50 mg po TID, may be increased to 100 mg po TID. Slower titration recommended for elderly or medically frail patients. Dose adjust for renal insufficiency.
ii.
Antidepressants (e.g., duloxetine (Cymbalta®) 30–60 mg po daily) for burning pain
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