TABLE 1.
Clinical, laboratory and management details of DC and PAVMs in study participants
| Patient | At DC/TBD Diagnosis | Telomere length |
Gene, mutation |
AA Treatment |
HCT indication |
Age at HCT |
HCT prep, GVHD prophylaxis |
At PAVM Diagnosis | Age at last follow- up |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age | Features of DC triad |
AA | Age | Presentation | DLCO (%predicted) |
Co- existent PF |
Positive TTCE |
Evidence of liver disease |
||||||||
| 1 | 13 | L | Mild | VL | TERT, c.2266C>T p. R756C | Oxymetholone, danazol | N/A | N/A | N/A | 15 | Cyanosis, hypoxia, clubbing | 16 | Y | Y | N | 25 |
| 2 | 27 | None | Moderate | VL* | RTEL1, c.2227G>A p.D734N + c.2684C>T p.P895L | Danazol | N/A | N/A | N/A | 32 | None | 52 | N | Y | N | 32 |
| 3 | 21 | None | Moderate | VL* | TERT, c.994G>A p.1062A>T+ c.844T>C p. S795P | Danazol | N/A | N/A | N/A | 27 | No symptoms, clubbing | 53 | N | Y | Hepatic fibrosis, splenomegaly, portal HTN | 27 |
| 4 NCI 291-1 | 18 | S, N | Moderate | VL | Compound het. PARN c.19A>C p.N7H; gene deletion | HCT | Severe thrombocytopenia** | 21 | Flu/Alem, CSA/MMF | 21 | Dyspnoea on exertion, clubbing | 28 | Y | Y | N | 24 |
| 5 NCI 216-1 | 8 | N, L | Severe | VL | UNK | HCT | AA | 9 | Flu/Bu/CPM/ATG, Tacro/ T cell depletion | 14 | Dyspnoea on exertion | 50 | Y | Y | N | 17 |
| 6 NCI 440-1 | 3.5 | S, N | Severe | VL | DKC1, c.1223C>T p.T408I | ATG/CSA, Androgen, G-CSF, Darbepoetin, HCT | AA | 7 | Flu/CPM/ATG, CSA/MMF | 12 | Dyspnoea, clubbing | 48 | N | N/A | N | 14 |
| 7 | 17 | S, N, L | None | N/A | TINF2 | HCT | MDS | 5 | TBI, CSA/MTX | 13 | Hypoxia, dyspnoea on exertion, clubbing | 18 | N | Y | N | d.19 |
| 8 NCI 297-2 | 16 | S, N, L | Severe | VL | RTEL1, c.3361delG p.A1121LfsX6, c.1338+3 A>G IVS15+3 A>G | HCT | AA | 19 | Flu/CPM/ Alem/TBI, Tacro/MMF | 22 | Dyspnoea | 56 | Y | Y | Mild hepatic fibrosis, Portal HTN | 22 |
| 9 NCI 349-1 | 5.5 | S, N, L | Severe | VL | TINF2, c.845G>A, p.R282H | HCT | AA | 5.7 | Flu/CPM/Alem/TBI, CSA/MMF | 12 | Dyspnoea, cough | N/A | Y | N/A | N | d. 13 |
| 10 | N/A | N/A | N/A | N/A | TINF2, c.845G>A, p.R282H | HCT | AA | 2.9 | Flu/Alem/CPM/Anti CD-45, CSA/MMF | 7 | Hypoxia | N/A | N | Y | N | 10 |
| 11 | 4 | S, N, L | Moderate | VL | TINF2, c.805C>T, p.Q269X | HCT | AA | 4.7 | Flu/Alem/Anti-CD45, Tacro | 10 | Progressive dyspnoea | N/A | Y | Y | Mild hepatic fibrosis, splenomegaly, portal HTN | 11 |
| 12 NCI 145-1 | 9 | S, N | Severe | VL | TINF2, c.844C>A p.R282S | HCT | AA | 10.8 | Flu/Bu/CPM/ATG, Tacro/T-cell depletion | 15 | Dyspnoea on exertion | 37 | N | N | Hepatic fibrosis, s/p splenectomy | d. 16 |
| 13 NCI 438-1 | 1 | N | Severe | VL | TINF2, c.844C>A p.R282S, | HCT | AA | 1.5 | Flu/CPM/ATG, CSA | 3 | Chronic hypoxia | N/A | N | Y | N | d. 4 |
Abbreviations: DC: Dyskeratosis congenita; TBD: telomere biology disorder; PAVM: Pulmonary arteriovenous malformation; S: Skin pigmentation; N: Dysplastic nails; L: Oral leukoplakia; AA: Aplastic anaemia; VL: Telomere length “very low”, < 1st percentile for age in all leukocyte subsets measured by Flow cytometry and fluorescence in situ hybridization (unless indicated by *); UNK: Causative gene unknown; HCT: Hematopoietic stem cell transplantation; ATG: Anti-thymocyte globulin; CSA: Cyclosporin; G-CSF: granulocyte colony stimulating factor; MDS: myelodysplastic syndrome; GVHD: graft versus host disease; Flu: Fludarabine; Alem; Alemtuzamab; MMF: mycophenolate mofetil; Bu: Busulfan; CPM: cyclophosphamide; Tacro: Tacrolimus ; MTX: Methotrexate; TBI: Total body irradiation; N/A: not available/ not applicable; DLCO: Diffusion lung capacity of carbon monoxide; PF: pulmonary fibrosis; TTCE: Transthoracic contrast echocardiogram; HTN: hypertension; s/p: status-post; Y: Yes; N: No
: telomere length < 1st percentile for age measured by qPCR;
: HCT for severe thrombocytopenia that was precluding candidacy for lung transplant
Age in years. d.: died