Table 6.

Treatment of Manifestations in Individuals with Dyskeratosis Congenita and Related Telomere Biology Disorders (DC/TBD)

Manifestation/
Concern		TreatmentConsiderations/Other
Bone marrow
failure 1 		If matched related donor is available: HCT 2 regardless of age
  • Range of clinical phenotypes seen in DC/TBD & possibility of non-manifesting or very mildly affected heterozygotes w/in families may complicate selection of related HCT donors. 3
  • Test potential related HCT donors either for pathogenic variant(s) present in proband or, if variant(s) are unknown, for telomere length.
If matched related donor is not available: HCT 2 from unrelated donor can be considered, although trial of androgen therapy (e.g., oxymetholone or danazol) may be considered 1st. 4
  • Persons w/DC/TBD may be more sensitive to androgens than those w/FA, & dose must be adjusted to ↓ side effects such as impaired liver function, virilization, or behavior problems (e.g., aggression, mood swings).
  • Side effects, incl liver enzyme abnormalities, need to be monitored carefully.
  • Perform baseline & follow-up liver ultrasound exams for persons receiving androgen therapy because of possibility of liver adenomas & carcinomas, which have been reported in FA & in persons using androgens for benign hematologic diseases or for non-hematologic disorders. 5
Hematopoietic growth factorsShould not be combined w/androgen therapy due to possible risk of splenic peliosis & rupture
Cancer Specific treatment should be tailored to type of cancer.Affected persons undergoing chemotherapy for cancer may be at ↑ risk for:
  • Prolonged cytopenias due to underlying BMF;
  • Therapy-related pulmonary & hepatic toxicity (PFTs & liver function should be monitored carefully);
  • Radiotherapy-related complications based on observations in persons undergoing radiotherapy in HCT. 6
Pulmonary
fibrosis 		Primarily supportive careLung transplantation may be considered in severe cases, although long-term outcomes have not been studied. 7
Liver disease Primarily supportive careLiver transplant may be considered in severe cases, although data on outcome are scarce.
General
health 		Childhood vaccinations (unless contraindicated due to immunodeficiency or HCT) incl influenza & human papillomavirus

BMF = bone marrow failure; FA = Fanconi anemia; HCT = hematopoietic cell transplantation; PFT = pulmonary function test

1.

Following the model of the Fanconi anemia consensus guidelines [Eiler et al 2008] and updated in the DC treatment guidelines [Savage & Cook 2015], treatment of bone marrow failure (BMF) is recommended if the hemoglobin is consistently below 8 g/dL, platelets are lower than 30,000/mm3, and neutrophils are below 1,000/mm3.

2.

HCT is the only curative treatment for severe BMF or leukemia in DC/TBD. It should be performed at centers experienced in treating DC/TBD. Pre- and post-transplant considerations and outcomes have been recently reviewed [Fioredda et al 2018, Bonfim 2020].

3.
4.
5.
6.

Author, personal observation

7.

From: Dyskeratosis Congenita and Related Telomere Biology Disorders

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