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Long term screening

Recognizing complications early when there are more effective treatment options is critical to the well-being of transplant recipients.

Complications from hematopoietic cell transplantation (HCT) can develop long after a patient leaves a transplant center and returns to a primary physician. Use these guidelines to deliver the specialized care transplant patients need to prevent late complications and to reduce morbidity.

These long-term screening guidelines are based on International Recommendations for Screening and Preventative Practices for Long-Term Survivors of Transplantation and Cellular Therapy: A 2023 Update, developed by experts across 29 international transplant institutions. [1]

The guidelines are organized by organ system to assist in patient care planning. Use the following charts to:
  • Become aware of the specialized care transplant recipients need
  • Plan for tests and treatments
  • Trigger discussions with patients on proper self-care

Cardiac & vascular complications

Recommendation
Frequency
Notes
Tests/procedures
Lipid panel
  • Low risk: At 6 months and then annually
  • High risk: Every 36 months
  • Less frequent testing reasonable for children
  • Multimodal weight loss program for obese adults
Hemoglobin A1c
  • Low risk: At 36 months and then annually
  • High risk: Every 6 months
Less frequent testing reasonable for children
Echocardiogram (Adults)
  • Within 1 year if anthracyclines ≥250 mg/m2, or with lower exposure and additional cardiomyopathy risk factors
  • As needed if without anthracycline exposure
  • Additional surveillance based on risk factors
  • Referral to cardiology if abnormal imaging and/or concerning symptoms
  • If available, consider referring to cardio-oncology program for those at very high risk
Echocardiogram (Children)
  • Additional surveillance based on risk factors
  • Referral to cardiology if abnormal imaging and/or concerning symptoms
  • If available, consider referring to cardio-oncology program for those at very high risk
Recommendations
Management of dyslipidemia
According to American Heart Association/American College of Cardiology recommendations or local guidance
N/A
Management of hypertension
According to population guidance
Measurement of blood pressure, weight, and body mass index (BMI) at each survivorship visit
Other considerations
Hurler syndrome
Close monitoring for cardiopulmonary dysfunction after HCT
N/A
Amyloidosis
v
N/A

Dermatologic

Recommendation
Frequency
Notes
Tests/procedures
Dermatologic exam
Risk factor dependent
  • Frequency/extent of examination tailored to individual risk factors: prior or present graft- versus-host disease (GVHD), sun exposure and radiation history, voriconazole exposure, family history, and history of skin cancer
  • Regular skin self-examination; refer to a dermatologist for further evaluation of suspicious lesions
  • Regular skin exam involves exposure of all body areas and includes manual palpation to detect sclerosis
Recommendations

Discuss risk of dermatologic complications

At comprehensive survivorship visits

  • Particularly related to chronic graft-versus-host disease (cGVHD), medications, and radiation
  • Advise to seek medical attention for non-healing skin lesions, skin tightening or other changes
Discuss sun exposure
At comprehensive survivorship visits
  • Advise to avoid direct sun exposure without appropriate protection: proper clothing, hats, applying UVA/UVB sunscreen to exposed areas
  • Particularly important for patients on immunosuppression, voriconazole, with a history of total body irradiation (TBI) or skin chronic GVHD

Endocrine complications

Recommendation
Frequency
Notes
Tests/procedures
Thyroid function test
At 1-year post-transplant or sooner if symptomatic, and annually thereafter
  • Thyroid stimulating hormone (TSH) and free T4 recommended
  • Central nervous system (CNS) radiation therapy is a risk factor for central hypothyroidism
Recommendations

Assessment of suspected growth abnormality

Routine monitoring

  • Should be evaluated and treated by an endocrinologist, weighing clinical risks vs. benefits of hormonal therapy
  • Routine assessment of growth velocity including height, weight, and BMI should be performed for children
Assessment of gonadal dysfunction
Annually
  • Assessment of menarche/ menstrual history and menopausal symptoms
  • Routine assessment of onset/ progression of puberty with tanner staging for children; increasing frequency when approaching puberty or with concerns
  • Gonadal assessment at 1year post-HCT in adults; subsequent frequency according to clinical needs
  • Involvement of appropriate subspecialties for potential HRT
Assessment for adrenal insufficiency
Monitoring as needed
Adrenocorticotropic hormone (ACTH) stimulation test for patients on long-term corticosteroids when weaning corticosteroids

Gastrointestinal complications

Recommendation
Frequency
Notes
Tests/procedures
Liver function testing (transaminases, total bilirubin, alkaline phosphatase)
  • Without risk factors: Every 12 months for the first year and then annually
  • With chronic hepatitis, chronic graft versus host disease (cGVHD) tapering immune suppression therapy (IST) beyond first year: More frequent monitoring
N/A
Other considerations

Hepatitis B virus (HBV) infection

  • Chronic HBV: Lifelong monitoring of HBV DNA at least every 2 months; HBV DNA and alanine aminotransferase (ALT) every month after withdrawing antivirals; prophylactic anti-HBV therapy should be considered regardless of HBV DNA levels to prevent reactivation; continue at least 1 year after IST withdrawal
  • Resolved HBV: HBV DNA monitoring at least every 2 months for at least 3 years after stopping IST; prophylactic anti-HBV therapy if unable to monitor HBV DNA, continue at least 3 years after IST withdrawal
N/A
Hepatitis C virus (HCV) infection
Chronic HCV: Routine HCV RNA testing at baseline and if getting HCV antiviral therapy or has unexplained ALT elevation; antiviral therapy if available and check liver function tests (LFT) and complete blood count (CBC) every 6-12 months
Cirrhosis
Monitor for varices, hepatocellular carcinoma (HCC), and other sequalae
Referral to hepatologist for monitoring
Dyskeratosis congenita
Frequent LFTs
Hepatologist referral if abnormalities noted

Hematologic

Recommendation
Frequency
Notes
Tests/procedures
Complete blood count
At each visit for at least 10 years post-HCT
If abnormal, repeat as needed
Ferritin
Regular monitoring until normalized
Nonspecific, initial screening test for iron overload

MRI (iron quantification)

To assess liver and cardiac iron levels when concern; follow-up as needed to follow progress after treatment

Risk based on transfusion history and HCT indication
Post-HCT phlebotomy
With confirmed iron overload; duration dependent on response
Consider iron chelation if ineligible for phlebotomy Resumption of menses in females may reduce iron
Recommendations
Venous thromboembolism (VTE) prophylaxis in patients with multiple myeloma
When receiving immunomodulatory imide drugs and chemotherapy and/or dexamethasone after HCT
N/A
Bleeding risk assessment
Prior to initiating anticoagulation
N/A
Other considerations
Hemoglobinopathy
  • Perform chimerism at least every 3 months in year 1 post-HCT and every 6 months thereafter
  • Further chimerism based on previous results
N/A
Hurler syndrome
Neurologic screening for spinal canal narrowing and carpal tunnel syndrome
N/A
Inherited bone marrow failure syndromes
Require specialized follow-up with a multidisciplinary specialist team
N/A

Immunity & infections

Recommendation
Frequency
Notes
Tests/procedures
Vaccination
Consider beginning inactivated vaccines at 3-6 months post-HCT
  • According to published guidelines, considering patient age and country recommendations
  • Includes patients with GVHD and/or on IST given higher risk of infection
Other considerations

Asplenia/functional asplenia

  • Vaccinate for S. pneumoniae and N. meningitidis (MCV4, group B)
  • Educate on sepsis/fever management
  • Consider antimicrobial prophylaxis
N/A
Hypogammaglobulinemia
Supplemental intravenous immunoglobulin (IVIg) may be considered for selected HCT recipients with IgG < 400 mg/dL (4 g/L): patients with recurrent sino-pulmonary infections; patients with very low levels (<200 mg/dL); or receiving anti-B cell or CAR T-cell therapy
N/A
Multiple myeloma
Specific antimyeloma medications warrant specific antimicrobial prophylaxis
N/A
Inborn errors of immunity
  • Pay careful attention to immune reconstitution and mixed chimerism
  • Assess lymphocyte subsets, mitogen proliferation, immunoglobulin levels and antibody responses every 3-6 months until normalized and as needed
N/A

Muscular

Recommendation
Frequency
Notes
Assess range of motion
At each clinic visit for patients with chronic GVHD
  • Ideally with medical photos for subsequent comparison
  • Encourage patients to also perform self-assessment
Other considerations
Glucocorticoids
  • Routinely evaluate patients on glucocorticoid treatment for glucocorticoid-induced myopathies; observe patient rising from a squatting position
  • Patients with/at risk for steroid myopathy should engage in physical activity and physical therapy; physiatry referral may be beneficial, low resistance exercise to prevent/slow loss of muscle mass
N/A

Myalgia/weakness

  • Chronic GVHD-associated polymyositis, statin toxicity, or myasthenia gravis should be included in differential diagnosis of myalgia/weakness if persistent or progressive
  • CPK, aldolase, anti-acetylcholine antibodies are a reasonable next step; if negative, muscle MRI, EMG or muscle biopsy may be considered.
N/A

Neurologic & cognitive

Recommendation
Frequency
Notes
Tests/procedures
Clinical assessment for peripheral nervous system (PNS) and central nervous system (CNS) dysfunction
At 6 and 12 months post-HCT, ≥yearly thereafter
  • Earlier and more frequent evaluation to be considered in high-risk patients
  • Careful history/examination/review of systems/medication history and assessment of time of onset of neurological signs and symptoms during survivorship visits
Audiologic evaluation
Within first year post-HCT
  • Patients with exposures to head and neck irradiation, platinum chemotherapy, aminoglycosides, or an inherited condition associated with hearing disability
  • Follow-up evaluations as clinically warranted

Neurocognitive testing

  • Pediatrics: Within first year post-HCT
  • Adults: As needed
  • Strongly consider before returning to work/school, major changes in school (i.e., moving from elementary to middle school), or changes in school performance
Recommendations
Council on hearing loss prevention
At initial survivorship visit
  • Council patients about hearing loss prevention and to seek assessment for new symptoms
  • Hearing loss may be present in adenosine deaminase (ADA) deficiency prior to HCT and require developmental support, regular otolaryngology, and audiological assessment post-HCT
Pediatrics: Discuss/monitor development/cognition
Annually
  • Can be performed by pediatrician
  • Educational/vocational progress assessment recommended
Adult: Screen for cognitive changes
At comprehensive survivorship visit
  • Query for cognitive function changes (may be subtle)
  • Inquire about difficulties multitasking, attention, remembering things or whether thinking feels slow
  • Exclude reversible causes of cognitive decline: depression, fatigue, insomnia, medication
  • Neurocognitive testing and imaging should be considered if functional impairment
Geriatric: Comprehensive geriatric assessment
At 6 and 12 months post-HCT
To identify patients more likely to benefit from enhanced toxicity risk prediction and aid treatment decision-making
Other considerations
Sickle cell disease (SCD)
All patients undergoing HCT for sickle cell disease should be offered neurocognitive testing posttherapy, if available
N/A

Ocular

Recommendation
Frequency
Notes
Tests/procedures
Ocular exam
At onset of any chronic GVHD, dry eye symptoms, changes in vision or other eye symptoms
  • NIH Consensus Development Project recommends consultation with an eye specialist every 3 months during the first year post-HCT and then at longer intervals thereafter
  • Monitoring of intraocular pressure (IOP) important in patients receiving any form of glucocorticoids
Recommendations

Question about eye concerns

At comprehensive survivorship visits

  • Advise to report dryness, light sensitivity, excessive tearing, foreign body sensation, pain, redness, swelling, mucoid aggregates, vision changes
  • Inform about risk of premature cataracts for TBI recipients
Other considerations
Hurler syndrome
Ongoing ophthalmologic assessment for glaucoma, cataracts, progression of corneal clouding
N/A

Oral & dental

Recommendation
Frequency
Notes
Tests/procedures
Evaluation by a dentist or oral medicine specialist
At 6 and 12 months post-HCT, ≥yearly thereafter
Earlier and more frequent evaluation to be considered in high-risk patients (e.g., Fanconi anemia, radiation to the head or neck, or refractory chronic GVHD)
Recommendations

Screen for chronic GVHD, high-risk habits

At comprehensive survivorship visit

  • Avoid smoking, vaping and chewing tobacco
  • Decrease regular intake of sugar containing beverages
  • Avoid intraoral piercing
Perform a thorough head, neck and oral exam
At comprehensive survivorship visit
N/A
HPV vaccination
According to published guidelines, considering patient age and country recommendations
N/A
Other considerations
Children
Perform oral and radiologic assessment for tooth development
N/A
Xerostomia
  • Should receive meticulous oral hygiene, undertake preventive measures for dental/ periodontal disease, and receive aggressive treatment of oral infections
  • Avoid trauma to oral mucosa
N/A

Psychosocial

Recommendation
Frequency
Notes
Tests/procedures
Mental health screening with standardized questionnaire
At comprehensive survivorship visits
  • Example: NCCN distress thermometer
  • No gold standard for screening mental health after HCT; take care to not overburden patients with patient reported outcome (PRO) tools
  • To guide clinical investigations or behavioral or psychological support, particularly if multiple somatic complaints, new GVHD, major life events or treatment changes
Recommendations

Review psychosocial and mental health

Day +100, +180, +365, then annually

  • Review current symptom patterns, distress, medications, comorbidities, and physical activity
  • Regularly inquire to level of spousal/caregiver psychological adjustment, family functioning, educational, vocational activities, and financial toxicity
  • Appropriate referral if necessary
  • Offer peer support and return to work/school programs
Discuss medication adherence
Ongoing
  • Set incremental goals for healthy diet (i.e., vegetables, fruits, whole grains, low in excess sugars, dried foods, red/processed meat, and dietary supplements), activity, weight management
  • Encourage adequate sleep and age-appropriate preventative measures
Discuss healthy lifestyle
Comprehensive survivorship visits
  • Set incremental goals for healthy diet (i.e., vegetables, fruits, whole grains, low in excess sugars, dried foods, red/processed meat, and dietary supplements), activity, weight management
  • Encourage adequate sleep and age-appropriate preventative measures
Other considerations
Adolescents and young adults
Provide transition of care education and plans
N/A
Persons with disabilities
Assess those with significant physical, visual, or auditory disabilities for appropriate support services and medical equipment needs
N/A

Renal & urinary complications

Recommendation
Frequency
Notes
Tests/procedures
Renal function testing
At 6 months, 1 year, and at least annually thereafter
  • Includes complete urinalysis, urine albumin to creatinine ratio, BUN/creatinine
  • More frequent monitoring for multiple myeloma and amyloidosis
  • Possible renal anomalies predisposing to chronic kidney disease (CKD) among patients with bone marrow failure syndromes, inborn errors of metabolism (IEM), or Artemis deficiency
Recommendations

Management of hypertension

Measurement of blood pressure, weight, and BMI at each survivorship visit

Respiratory

Recommendation
Frequency
Notes
Tests/procedures
Pulmonary function tests (PFT) screening
Every 3 months for the first year after HCT, every 6 months for the second year, and then annually for 5 years after HCT (or until final adult height in children, whichever occurs later)
  • Spirometry and hemoglobin corrected diffusing capacity of the lungs for carbon monoxide (DLCO) age
  • Age <6 years: if unable to perform, can consider alternative screening with pulse oximetry, multiple breath washout testing, parametric mapping by CT
CT chest Imaging
At onset of pulmonary symptoms or abnormal PFTs

N/A

Recommendations

Pulmonary consultation
At onset of pulmonary symptoms or abnormal PFT
Especially in setting of irreversible air flow obstruction
Vaccination against respiratory pathogens
Consider beginning inactivated vaccines at 3-6 months post-HCT
According to published guidelines, considering patient age and country recommendations
Counsel on avoidance of tobacco, smoking, vaping
At comprehensive survivorship visit
N/A
Other considerations
Dyskeratosis congenita
  • Perform PFTs at regular intervals post-HCT
  • Refer to pulmonologist with any abnormalities
N/A
Chronic GVHD
PFTs at initial diagnosis then at least spirometry every 3-6 months until discontinuation of all systemic immunosuppressive therapy
N/A

Sexual health, fertility & pregnancy

Recommendation
Frequency
Notes
Tests/procedures
Fertility assessment
As age appropriate and for those contemplating future parenthood
  • Semen analysis or assessment of ovarian function
  • Discussion about risk of premature menopause
  • Fertility specialist consult for those desiring pregnancy to understand fertility potential and options (i.e. IVF, donor gamete)
  • Contraception advised for those wishing to avoid parenthood
Recommendations

Sexual activity

As appropriate

Counseling regarding safe sex practices and contraceptive options
Sexual function
Discuss at 36 months post-HCT and then continue annually
  • Prompt referral for medical or psychosocial needs for patient and partner as necessary
  • Assessment of hypogonadism and/or urogenital GVHD with appropriate gynecology or genitourinary team referral
Pregnancy
As appropriate
Patients should be followed throughout pregnancy by expert in high-risk obstetrics and may require review by an anesthetist prior to delivery
Other considerations
Pregnant women with systolic dysfunction/ cardiac risk factors
Cardiology follow-up during pregnancy
N/A
Those with underlying genetic disorder/ cancer predisposition syndrome
Genetic counseling prior to pregnancy
N/A
Women exposed to uterine radiation and desiring pregnancy
Counsel on risk of uterine factor infertility
N/A

Skeletal

Recommendation
Frequency
Notes
Tests/procedures
DEXA
  • Standard risk: At 1-year post-HCT
  • High risk: At 3 months post-HCT
  • If abnormal, repeat Q1-2 years, sooner if ongoing risks or response assessment
  • <5 years old, lumbar spine bone mineral density (BMD) may be measured; DEXA hip measurements less reliable for age <13.
  • FRAX and vertebral fracture assessment (VFA) may help evaluation/management
Recommendations

Optimize calcium and vitamin D intake

At comprehensive survivorship visits

Vitamin D may be measured regularly in those at deficiency risk
Recommend weight-bearing exercise
At comprehensive survivorship visits
N/A
Discuss hormone replacement therapy
As needed
Patients with hypogonadism if age appropriate, and not otherwise contraindicated
Other considerations
Bisphosphonates
  • Consider bisphosphonates in high-risk patients, significant abnormalities on DEXA or FRAX assessments, or fragility fractures
  • Bisphosphonate choice made with consideration of the patient’s presentation, renal function, and respective adverse events
  • For patients with multiple myeloma (MM), supportive management with use of bisphosphonates for at least 2 years
N/A
Avascular necrosis (AVN)
  • Maintain a high index of suspicion for AVN risks include prior AVN, radiation exposure or prolonged glucocorticoids
  • Routine imaging screening for asymptomatic AVN not indicated
  • Symptomatic patients: non-contrast MRI is the most sensitive way to confirm and stage AVN; once diagnosis of AVN prompt referral to orthopedic specialist recommended
N/A
Hurler syndrome
Neurologic screening for spinal canal narrowing and carpal tunnel syndrome
N/A

Subsequent malignant neoplasm

Recommendation
Frequency
Notes
Tests/procedures
CBC/therapy-related myeloid neoplasms (tMN) screening
High risk: Annual for ≥10 years
  • High risk: Consider more frequent screening (i.e., chemotherapy, age; autologous HCT)
  • Attention to unexplained cytopenias, macrocytosis, or cellular atypia
Epstein-Barr virus (EBV) DNA screening
Variable
For prevention of PTLD in high-risk patients (e.g., ATG, alemtuzumab, ex-vivo T-cell depletion)

Cervical cancer screening/pap smear

Most: Variable
Fanconi anemia (FA): Annual

  • For most, screening interval based on attained age and risk factors
  • FA: Starting in adolescence
Oral exam
Most: Annually
High risk: Every 6 months
  • High risk: Oral chronic GVHD, tobacco use, FA
  • Advise reporting non-healing lesions, leukoplakia, localized pain, changes in mucosal color/texture
Esophagogastroduodenoscopy (EGD)
Variable
Endoscopic screening for esophageal cancer may be considered in high-risk patients (chronic GVHD receiving prolonged immunosuppression, symptoms of gastroesophageal reflux, dysphagia)
Colonoscopy/colorectal cancer screening (CRC)
Variable
  • Pediatric survivors <age 45 years and radiation therapy (RT) exposed: CRC screening colonoscopy or multitarget stool DNA screening at 5 years post-RT exposure or age 30 years, whichever occurs later
  • Adult survivors: As part of shared decision making, consider exposed to abdominal/pelvic RT or TBI who underwent HCT at ≥25 years of age, colonoscopy beginning 5 years post-RT exposure and no later than age 45 years
  • Screen patients without RT exposure according to general population guidelines, individual risk factors/family history
  • Screen patients with colon Cancer Predisposition Syndrome (CPS) [e.g., hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), diamond blackfan anemia (DBA)] based on underlying CPS
  • Risk in those exposed to TBI likely dose dependent; lower doses may not increase the risk to level that risk/benefit of early colonoscopy warranted
Breast cancer/mammography/breast MRI
Variable
  • Female recipients of TBI or chest RT should begin breast cancer screening with mammogram and breast MRI (if available) at age 25-, or 8-years post-RT, whichever occurs later, but no later than age 40
  • Survivors without additional risk factors should participate in regular annual mammograms/ clinical breast exam according to general population guidelines for geographical region and individual risk factors including family history
Thyroid exam
Annually
  • Patients should have an annual thyroid exam and review of potential symptoms of thyroid cancer
  • As part of shared decision making, consider ultrasound screening in patients who received thyroid RT; Routine use of thyroid ultrasound may not provide additional benefit; some groups recommended
  • Screen patients with inherited thyroid CPS (e.g., multiple endocrine neoplasia, FAP) based on underlying condition
Brain MRI
Variable
As part of shared decision making, consider meningioma screening in patients who received CNS RT
Recommendations
General counseling
At comprehensive survivorship visits
  • Based on treatment exposures, time from exposure, chronic GVHD history, and other modifying factors
  • Encourage to avoid high-risk behaviors, unhealthy diet (e.g., tobacco and vaping, passive tobacco exposure, alcohol abuse; high fat/low fiber diet)
Breast cancer risk counseling
At comprehensive survivorship visits
  • In high-risk individuals, discussion with appropriate experts on risk reduction strategies (i.e., prophylactic mastectomy, prophylactic medical therapies, lifestyle)
  • Counsel on additional breast cancer risk factors (i.e., BRCA1/2, family history)
Other considerations
Epstein-Barr virus (EBV) viremia
  • Recommend pre-emptive treatment with Rituximab
  • Note: PTLD evaluation includes LN palpation, review of B-symptoms (fever, drenching night sweats, ≥10% weight loss over 6 months)
N/A
Human papillomavirus (HPV)
  • HPV vaccination according to country-specific general population recommendations, unless otherwise contraindicated
  • Note: HPV role in mucocutaneous/ genital cancers post-HCT unclear
N/A
Fanconi anemia
Survivors with mutations in BRCA2 (FANCD1) or PALB2 (FANCN) require screening for specific solid cancers
N/A

Multiple formats to meet your needs

Other ways you can access these long-term screening guidelines:

We also offer the guidelines using patient-friendly language:

References


  1. Rotz SJ, Bhatt NS, Hamilton BK, et al. (2024). International recommendations for screening and preventative practices for long-term survivors of transplantation and cellular therapy: A 2023 update. Transplantation and Cellular Therapy, 30(4) 349-385. DOI: 10.1016/j.jtct.2023.12.001.