Table 1.

Summary recommendations for screening and prevention of late complications in long-term HCT survivors

Tissues/organs	Late Complications	General Risk Factors	Monitoring Tests	Monitoring Tests and Preventive Measures In All HCT Recipients	Monitoring Tests and Preventive Measures In Special Populations
Immune system	-Infections	-Donor source -HLA disparity -T-cell depletion -GVHD -Prolonged immunosuppression -Venous access devices	-CMV antigen or PCR in patients at high risk for CMV reactivation	-PCP prophylaxis for initial 6 months after HCT -Immunizations post-transplant according to published guidelines -Administration of antibiotics for endocarditis prophylaxis according to American Heart Association guidelines	-Patients with cGVHD: Antimicrobial prophylaxis targeting encapsulated organisms and PCP for the duration of immunosuppressive therapy -Patients with cGVHD: Screening for CMV reactivation should be based on risk factors, including intensity of immunosuppression.
Ocular	-Cataracts -Sicca syndrome -Microvascular retinopathy	-TBI/radiation exposure to head and neck -Corticosteroids -GVHD	-Ophthalmologic exam	-Routine clinical evaluation at 6 months and 1 year after HCT and at least yearly thereafter -Ophthalmologic examination with measurement of visual acuity and fundus examination at 1 year after HCT, subsequent evaluation based on findings and risk-factors -Prompt ophthalmologic examination in patients with visual symptoms	-Patients with cGVHD: Routine clinical evaluation, and if indicated, ophthalmologic examination more frequently
Oral	-Sicca syndrome -Caries	-GVHD -TBI/radiation exposure to head and neck	-Dental assessment	-Education about preventive oral health practices -Clinical oral assessment at 6 months and 1 year after HCT and at least yearly thereafter with particular attention to intra-oral malignancy evaluation -Dental assessment at 1 year after HCT and then at least yearly thereafter	-Pediatric recipients: Yearly assessment of teeth development -Patients with cGVHD: Consider more frequent oral and dental assesments with particular attention to intra-oral malignancy evaluation
Respiratory	-Idiopathic pneumonia syndrome -Bronchiolitis obliterans syndrome -Cryptogenic organizing pneumonia -Sino-pulmonary infections	-TBI/radiation exposure to chest -GVHD -Infectious agents -Allogeneic HCT -Busulfan exposure	-PFT’s -Radiologic studies (e.g. chest X-ray, CT scan)	-Routine clinical evaluation at 6 months and 1 year after HCT and at least yearly thereafter -Assessment of tobacco use and couselling against smoking -PFT’s and focused radiologic assessment for allogeneic HCT recipients with symptoms or signs of lung compromise	-Patients with cGVHD: Some experts recommend earlier and more frequent clinical evaluation and PFT’s
Cardiac and vascular	-Cardiomyopathy -Congestive heart failure -Arrhythmias -Valvular anomaly -Coronary artery disease -Cerebrovascular disease -Peripheral arterial disease	-Anthracycline exposure -TBI/radiation exposure to neck or chest -Older age at HCT -Allogeneic HCT -Cardiovascular risk-factors before/after HCT -Chronic kidney disease -Metabolic syndrome	-Cumulative dose of anthracyclines -Echocardiogram with ventricular function, ECG in patients at risk and in symptomatic patients -Fasting lipid profile (including HDL-C, LDL-C and triglycerides) -Fasting blood sugar	-Routine clinical assessment of cardiovascular risk factors as per general health maintenance at 1 year and at least yearly thereafter -Education and counseling on “heart“ healthy lifestyle (regular exercise, healthy weight, no smoking, dietary counseling) -Early treatment of cardiovascular risk factors such as diabetes, hypertension and dyslipidemia -Administration of antibiotics for endocarditis prophylaxis according to American Heart Association guidelines
Liver	-GVHD -Hepatitis B -Hepatitis C -Iron overload	-Cumulative transfusion exposure -Risk factors for viral hepatitis transmission	-LFT’s -Liver biopsy -Serum ferritin -Imaging for iron overload (MRI or SQUID)	-LFT’s every 3–6 months in the first year, then individualized, but at least yearly thereafter -Monitor viral load by PCR for patients with known hepatitis B or C, with liver and infectious disease specialist consultation -Consider liver biopsy at 8–10 years after HCT to assess cirrhosis in patients with chronic HCV infection -Serum ferritin at 1 year after HCT in patients who have received RBC transfusions; consider liver biopsy or imaging study for abnormal results based on magnitude of elevation and clinical context; subsequent monitoring is suggested for patients with elevated LFT’s, continued RBC transfusions, or presence of HCV infection
Renal and genitourinary	-Chronic kidney disease -Bladder dysfunction -Urinary tract infections	-TBI -Drug exposure (e.g. calcineurin inhibitors, amphotericin, aminoglycosides) -CMV -Hemorrhagic cystitis	-Urine protein -Serum creatinine -BUN	-Blood pressure assessment at every clinic visit, with aggressive hypertension management -Assess renal function with BUN, creatinine and urine protein at 6 months, 1 year and at least yearly thereafter -Consider further workup (kidney biopsy or renal ultrasound) for for further workup of renal dysfunction as clinically indicated
Muscle and connective tissue	-Myopathy -Fascitis/scleroderma -Polymyositis	-Corticosteroids -GVHD	-Evaluate ability to stand from a sitting position -Clinical evaluation of joint range of motion	-Follow general population guidelines for physical activity -Frequent clinical evaluation for myopathy in patients on corticosteroids	-Patients with cGVHD: Physical therapy consultation in patients with prolonged corticosteroid exposure, fascitis or scleroderma -Patients with cGVHD: Frequent clinical evaluation by manual muscle tests or by assessing ability to go from sitting to standing position for patients on prolonged corticosteroids
Skeletal	-Osteopenia/osteoporosis -Avascular necrosis	-Inactivity -TBI -Corticosteroids -GVHD -Hypogonadism -Allogeneic HCT	-Dual photon densitometry -MRI to evaluate patients with joint symptoms	-Dual photon densitometry at 1 year for adult women, all allogeneic HCT recipients and patients who are at high risk for bone loss; subsequent testing determined by defects or to assess response to therapy -Physical activity, vitamin D and calcium supplementation to prevent loss of bone density	-Patients with cGVHD: Consider dual photon densitometry at an earlier date in patients with prolonged corticosteroid or calcineurin inhibitor exposure.
Nervous system	-Leukoencephalopathy -Late infections -Neuropsychological and cognitive deficits -Calcineurin neurotoxicity -Peripheral neuropathy	-TBI/radiation exposure to head -GVHD -Exposure to fludarabine -Intrathecal chemotherapy	-	-Clinical evaluation for symptoms and signs of neurologic dysfunction at 1 year and yearly thereafter -Diagnostic testing (e.g., radiographs, nerve conduction studies) for those with symptoms or signs	-Pediatric recipients: Annual assessment for congnitive development milestones
Endocrine	-Hypothyroidism -Hypoadrenalism -Hypogonadism -Growth retardation	-TBI/radiation exposure (e.g. head and neck, CNS) -Corticosteroids -Young age at HCT -Chemotherapy exposure	-Thyroid function tests -FSH, LH, testosterone -Growth velocity in children	-Thyroid function testing yearly post-HCT, or if relevant symptoms develop -Clinical and endocrinologic gonadal assessment for post-pubertal women at 1 year, subsequent followup based on menopausal status -Gonadal function in men, including FSH, LH and testosterone, should be assessed as warranted by symptoms	-Pediatric recipients: Clinical and endocrinologic gonadal assessment for pre-pubertal boys and girls within 1 year of transplant, with further followup as determined in consultation with a pediatric endocrinologist -Pediatric recipients: Monitor growth velocity in children annually; assessment of thyroid, and growth hormone function if clinically indicated -Patients with cGVHD: Slow terminal tapering of corticosteroids for those with prolonged exposure -Patients with cGVHD: Consider stress doses of corticosteroids during acute illness for patients who have received chronic corticosteroids
Mucocutaneous	-Cutaneous sclerosis -Genital GVHD	-GVHD -TBI/radiation exposure to pelvis	-Pelvic exam	-Counsel patients to perform routine self exam of skin and avoid excessive exposure to sunlight without adequate protection -Annual gynecologic exam in women to detect early involvement of vaginal mucosa by GVHD	-Patients with cGVHD and TBI recipients: Consider more frequent gynecologic evaluation based on clinical symptoms
Second cancers	-Solid tumors -Hematologic malignancies -PTLD	-GVHD -TBI/radiation exposure -T-cell depletion -Exposure to alkylating agents or etoposide	-Mammogram -Screening for colon cancer (e.g. colonscopy, sigmoidoscopy, fecal occult blood testing) -Pap smear	-Counsel patients about risks of secondary malignancies annually and encourage them to perform self exam (e.g. skin, testicles/genitalia) -Counsel patients to avoid high risk behaviors (e.g. smoking) -Follow general population recommendations for cancer screening	-Patients with cGVHD: Clinical and dental evaluation with particular attention towards oral and pharyngeal cancer -TBI and chest irradiation recipients: Screening mammography in women starting at age 25 or 8 years after radiation exposure, whichever occurs later but no later than age 40
Psychosocial and sexual	-Depression -Anxiety -Fatigue -Sexual dysfunction	-Prior psychiatric morbidity -Hypogonadism	-Psychological evaluation	-Clinical assessment throughout recovery period, at 6 months, 1 year and annually thereafter, with mental health professional counseling recommended for those with recognized deficits -Encouragement of robust support networks -Regularly assess level of spousal/caregiver psychological adjustment and family functioning -Query adults about sexual function at 6 months, 1 year and at least annually thereafter
Fertility	-Infertility	-TBI/radiation exposure -Chemotherapy exposure	-FSH, LH levels	-Consider referral to appropriate specialists for patients who are contemplating a pregnancy or are having difficulty conceiving -Counsel sexually active patients in the reproductive age group about birth control post-HCT
General health				-Recommended screening as per general population (see text)

HCT indicates hematopoietic cell transplantation; cGVHD, chronic graft-versus-host disease; CMV, cytomegalovirus; PCR, polymerase chain reaction; PCP, Pneumocystis pneumonia; TBI, total body irradiation; PFT’s, pulmonary function tests; CT, computed tomography; ECG, electrocardiogram; LFT’s, liver function tests; MRI; magnetic resonance imaging; SQUID, superconducting quantum interference device; HCV, hepatitis C; RBC, red blood cell; BUN, blood urea nitrogen; CNS, central nervous system; FSH, follicle stimulating hormone; LH, luteinizing hormone; PTLD, post-transplant lymphoproliferative disorder;