Recommended surveillance in adults with telomere biology disorders
| General recommendations | |
| • Regular use of sunscreen, avoid excessive sun exposure • Avoid exposure to cigarette smoke • Patient should be taught how to perform a monthly self-examination for oral, head and neck cancer • Maintain good oral hygiene • Vitamin D and calcium as needed to optimize bone health | |
| Basic surveillance | |
| Hematology | Baseline • CBC with differential and reticulocyte count • BM aspiration and biopsy • Conventional and molecular cytogenetics • Consider NGS myeloid panel to assess for somatic variants/clones. Monitoring • CBC normal/no cytogenetic abnormality: CBC every 6-12 months. BM evaluation if cytopenia develops. • Mild cytopenias/no cytogenetic abnormality: CBC every 3-4 months. BM evaluation based on clinical development, consider regular intervals (eg, every 1-3 years). • Abnormal cytogenetics: clonal cytogenetic abnormalities require more frequent CBC/BM evaluation to evaluate potential leukemic or MDS progression; intervals depend on development of CBC counts. High-risk abnormalities such as chromosome 7 change need immediate referral to HCT center. • Progressive decline or rise in blood counts require CBC and BM evaluation based on clinical situation. • On androgen therapy: CBCs prior to therapy; repeat CBCs every 4-6 weeks to assess response, when counts are stable every 2-3 months |
| Dermatology | Baseline and monitoring • Perform regular skin self-examination for new or changing skin growth • Annual dermatologist evaluation* |
| ENT | Baseline and monitoring • Annual cancer screening by an otolaryngologist |
| Dentist | Baseline and monitoring • Dental hygiene and screening every 6 months |
| Pulmonology | Baseline • Pulmonary function test • Consider HRCT based on results and risk factors Monitoring • Annual pulmonary function test • HRCT as clinically indicated Bubble echocardiogram for pulmonary symptoms in the absence of pulmonary fibrosis |
| Gastroenterology/ hepatology | Baseline • Evaluate for risk factors for hepatic disease (alcohol, drug use) • Liver function tests • Liver ultrasound and/or fibroscan • Evaluate for clinical signs of esophageal stenosis Monitoring • Liver function tests annually • Consider imaging (fibroscan/ultrasound) every 2 years • On androgen therapy: Check liver function tests prior to starting and every 1-2 weeks for first month, then every 6-12 weeks. Check lipid profile prior to starting and every 6-12 months. Perform liver ultrasound examination prior to starting androgens and semiannually to evaluate for adenomas, carcinomas, or fibrosis |
| Gynecology/ obstetrics | Baseline and monitoring: • Annual gynecologic evaluation with HPV testing starting at 18 years of age or at start of sexual activity • HPV vaccination in females and males <27 years of age if not adequately vaccinated in childhood Pregnancy: referral to maternal-fetal medicine specialist for high-risk pregnancy |
| Orthopedics | Bone density scan at baseline† |
| Oncology | • Follow surveillance guidelines for breast cancer, cervical cancer, colon/rectal cancer, lung cancer, prostate cancer • In case of cancer diagnosis: increased sensitivity to therapeutic radiation and chemotherapy may require dose reductions |
| Additional surveillance based on clinical presentation per case | |
| Cardiology | Regular assessment for hypertension Baseline lipid level |
| Urology | Baseline assessment for genitourinary anomalies, including symptoms of urethral stenosis, penile leukoplakia |
| Immunology‡ | In case of suspected immunodeficiency such as increased sinus/lung infections: • Serum immunoglobulin levels (total and fractions) • Flow cytometry for peripheral blood leukocytes including lymphocyte subsets • Consider evaluating childhood vaccine antibody titers |
| Neurology‡ | MRI assessment for cerebellar hypoplasia in individuals with developmental delay or learning problems |
| Ophthalmology‡ | Annual examination to detect/correct vision problems, abnormally growing eyelashes, lacrimal duct stenosis, retinal changes, bleeding, cataracts, and glaucoma |
| General recommendations | |
| • Regular use of sunscreen, avoid excessive sun exposure • Avoid exposure to cigarette smoke • Patient should be taught how to perform a monthly self-examination for oral, head and neck cancer • Maintain good oral hygiene • Vitamin D and calcium as needed to optimize bone health | |
| Basic surveillance | |
| Hematology | Baseline • CBC with differential and reticulocyte count • BM aspiration and biopsy • Conventional and molecular cytogenetics • Consider NGS myeloid panel to assess for somatic variants/clones. Monitoring • CBC normal/no cytogenetic abnormality: CBC every 6-12 months. BM evaluation if cytopenia develops. • Mild cytopenias/no cytogenetic abnormality: CBC every 3-4 months. BM evaluation based on clinical development, consider regular intervals (eg, every 1-3 years). • Abnormal cytogenetics: clonal cytogenetic abnormalities require more frequent CBC/BM evaluation to evaluate potential leukemic or MDS progression; intervals depend on development of CBC counts. High-risk abnormalities such as chromosome 7 change need immediate referral to HCT center. • Progressive decline or rise in blood counts require CBC and BM evaluation based on clinical situation. • On androgen therapy: CBCs prior to therapy; repeat CBCs every 4-6 weeks to assess response, when counts are stable every 2-3 months |
| Dermatology | Baseline and monitoring • Perform regular skin self-examination for new or changing skin growth • Annual dermatologist evaluation* |
| ENT | Baseline and monitoring • Annual cancer screening by an otolaryngologist |
| Dentist | Baseline and monitoring • Dental hygiene and screening every 6 months |
| Pulmonology | Baseline • Pulmonary function test • Consider HRCT based on results and risk factors Monitoring • Annual pulmonary function test • HRCT as clinically indicated Bubble echocardiogram for pulmonary symptoms in the absence of pulmonary fibrosis |
| Gastroenterology/ hepatology | Baseline • Evaluate for risk factors for hepatic disease (alcohol, drug use) • Liver function tests • Liver ultrasound and/or fibroscan • Evaluate for clinical signs of esophageal stenosis Monitoring • Liver function tests annually • Consider imaging (fibroscan/ultrasound) every 2 years • On androgen therapy: Check liver function tests prior to starting and every 1-2 weeks for first month, then every 6-12 weeks. Check lipid profile prior to starting and every 6-12 months. Perform liver ultrasound examination prior to starting androgens and semiannually to evaluate for adenomas, carcinomas, or fibrosis |
| Gynecology/ obstetrics | Baseline and monitoring: • Annual gynecologic evaluation with HPV testing starting at 18 years of age or at start of sexual activity • HPV vaccination in females and males <27 years of age if not adequately vaccinated in childhood Pregnancy: referral to maternal-fetal medicine specialist for high-risk pregnancy |
| Orthopedics | Bone density scan at baseline† |
| Oncology | • Follow surveillance guidelines for breast cancer, cervical cancer, colon/rectal cancer, lung cancer, prostate cancer • In case of cancer diagnosis: increased sensitivity to therapeutic radiation and chemotherapy may require dose reductions |
| Additional surveillance based on clinical presentation per case | |
| Cardiology | Regular assessment for hypertension Baseline lipid level |
| Urology | Baseline assessment for genitourinary anomalies, including symptoms of urethral stenosis, penile leukoplakia |
| Immunology‡ | In case of suspected immunodeficiency such as increased sinus/lung infections: • Serum immunoglobulin levels (total and fractions) • Flow cytometry for peripheral blood leukocytes including lymphocyte subsets • Consider evaluating childhood vaccine antibody titers |
| Neurology‡ | MRI assessment for cerebellar hypoplasia in individuals with developmental delay or learning problems |
| Ophthalmology‡ | Annual examination to detect/correct vision problems, abnormally growing eyelashes, lacrimal duct stenosis, retinal changes, bleeding, cataracts, and glaucoma |
Surveillance recommendations are modified from Niewisch and Savage55 and based on expert opinion in Agarwal et al. (published on www.teamtelomere.org) and Walsh et al.56 These recommendations are tailored toward individuals above 18 years of age without previous HCT. Following HCT, surveillance intervals may need to be adjusted.
Cutaneous squamous cell carcinomas have frequently been described in young adults with TBDs.15 Regular dermatologic exams may therefore be advisable starting before the age of 30 years.
TBDs in younger patients have an increased risk of avascular osteonecrosis and unexplained fractures. Therefore, a baseline bone density scan is advisable even in young adults.
Immunodeficiency (commonly with lymphopenia) and developmental delay (often cerebellar hypoplasia) is predominantly observed in TBD cases with onset in early childhood, specifically Hoyeraal-Hreidarsson syndrome. Ophthalmologic manifestations are frequent in childhood-onset TBDs, including classic dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome, Revesz syndrome, or Coats plus.
BM, bone marrow; CBC, complete blood count; HPV, human papilloma virus; NGS, next generation sequencing.