Severe clinical complications in combined clinic and field cohort patients according to mode of inheritance
| Number of patients . | Total, n (%) 231 . | AD, n (%) 112 . | AR/XLR, n (%) 63 . | TINF2, n (%) 25 . | Unknown, n (%) 31 . |
|---|---|---|---|---|---|
| Number of patients with HCT | 70 | 20 | 27 | 15 | 8 |
| Median age at diagnosis in years [range]* | 19.4 [0-71.6] | 36.1 [0.7-69.4] | 11.3 [0-45.9] | 8.1 [0-71.6] | 13.2 [1.2-56.7] |
| Median age at follow-up in years [range] | 29.6 [1.3-82.2] | 42.9 [2.4- 82.2] | 21.1 [1.4-54.2] | 19.3 [4.6-79.6] | 18.2 [1.3-57.6] |
| Number deceased at last follow-up [median age at death, range] | 97 [29.6,1.3-82.2] | 31 [53.7, 2.4- 82.2] | 38 [22.7,1.4-54.2] | 14 [16.4, 4.6-79.6] | 14 [22.3, 1.3-57.6] |
| Severe BMF† | 111 (48.1) | 33 (29.5) | 44 (69.8) | 19 (76) | 15 (48.4) |
| Pulmonary disease | |||||
| Pulmonary fibrosis | |||||
| Prior to HCT | 33 (14.3) | 22 (19.6) | 6 (9.5) | 2 (8) | 3 (9.7) |
| Following HCT | 13 (18.6) | 1 (5) | 6 (22.2) | 5 (33.3) | 1 (12.5) |
| PAVM | |||||
| Prior to HCT | 1 (0.4) | 0 | 1 (1.6) | 0 | 0 |
| Following HCT | 11 (15.7) | 1 (5) | 6 (22.2) | 4 (26.7) | 0 |
| Severe liver disease‡ | |||||
| Prior to HCT | 12 (5.2) | 2 (1.8) | 6 (9.5) | 0 | 4 (12.9) |
| Following HCT | 9 (12.9) | 2 (10) | 3 (11.1) | 3 (20) | 1 (12.5) |
| Gastrointestinal complications | |||||
| Esophageal strictures | 23§ (10) | 2 (1.8) | 14 (22.2) | 0 | 7 (22.6) |
| GI telangiectasia | |||||
| Prior to HCT | 9 (3.9) | 2 (1.8) | 5 (7.9) | 0 | 2 (6.5) |
| Following HCT | 6 (8.6) | 1 (5) | 2 (7.4) | 2 (13.3) | 1 (12.5) |
| Avascular osteonecrosis | |||||
| Prior to HCT | 20 (8.7)ǁ | 10 (8.9) | 7 (11.1) | 2 (8) | 1 (3.2) |
| Following HCT | 9 (12.9) | 3 (15) | 4 (14.8) | 2 (13.3) | 0 |
| Myelodysplastic syndrome | 17 (7.4) | 12 (10.7) | 4 (6.3) | 0 | 1 (3.2) |
| Cancer¶ | |||||
| Prior to HCT | 27 (11.7) | 13 (11.6) | 8 (12.7) | 1 (4) | 5 (16.1) |
| Leukemia | 7 (3) | 5 (4.5) | 1 (1.6) | 0 | 1 (3.2) |
| Solid tumor# | 20 (8.7) | 8 (7.1) | 7 (11.1) | 1 (4) | 4 (12.9) |
| Following HCT | 5 (7.1) | 0 | 2 (7.4) | 3 (20) | 0 |
| Number of patients . | Total, n (%) 231 . | AD, n (%) 112 . | AR/XLR, n (%) 63 . | TINF2, n (%) 25 . | Unknown, n (%) 31 . |
|---|---|---|---|---|---|
| Number of patients with HCT | 70 | 20 | 27 | 15 | 8 |
| Median age at diagnosis in years [range]* | 19.4 [0-71.6] | 36.1 [0.7-69.4] | 11.3 [0-45.9] | 8.1 [0-71.6] | 13.2 [1.2-56.7] |
| Median age at follow-up in years [range] | 29.6 [1.3-82.2] | 42.9 [2.4- 82.2] | 21.1 [1.4-54.2] | 19.3 [4.6-79.6] | 18.2 [1.3-57.6] |
| Number deceased at last follow-up [median age at death, range] | 97 [29.6,1.3-82.2] | 31 [53.7, 2.4- 82.2] | 38 [22.7,1.4-54.2] | 14 [16.4, 4.6-79.6] | 14 [22.3, 1.3-57.6] |
| Severe BMF† | 111 (48.1) | 33 (29.5) | 44 (69.8) | 19 (76) | 15 (48.4) |
| Pulmonary disease | |||||
| Pulmonary fibrosis | |||||
| Prior to HCT | 33 (14.3) | 22 (19.6) | 6 (9.5) | 2 (8) | 3 (9.7) |
| Following HCT | 13 (18.6) | 1 (5) | 6 (22.2) | 5 (33.3) | 1 (12.5) |
| PAVM | |||||
| Prior to HCT | 1 (0.4) | 0 | 1 (1.6) | 0 | 0 |
| Following HCT | 11 (15.7) | 1 (5) | 6 (22.2) | 4 (26.7) | 0 |
| Severe liver disease‡ | |||||
| Prior to HCT | 12 (5.2) | 2 (1.8) | 6 (9.5) | 0 | 4 (12.9) |
| Following HCT | 9 (12.9) | 2 (10) | 3 (11.1) | 3 (20) | 1 (12.5) |
| Gastrointestinal complications | |||||
| Esophageal strictures | 23§ (10) | 2 (1.8) | 14 (22.2) | 0 | 7 (22.6) |
| GI telangiectasia | |||||
| Prior to HCT | 9 (3.9) | 2 (1.8) | 5 (7.9) | 0 | 2 (6.5) |
| Following HCT | 6 (8.6) | 1 (5) | 2 (7.4) | 2 (13.3) | 1 (12.5) |
| Avascular osteonecrosis | |||||
| Prior to HCT | 20 (8.7)ǁ | 10 (8.9) | 7 (11.1) | 2 (8) | 1 (3.2) |
| Following HCT | 9 (12.9) | 3 (15) | 4 (14.8) | 2 (13.3) | 0 |
| Myelodysplastic syndrome | 17 (7.4) | 12 (10.7) | 4 (6.3) | 0 | 1 (3.2) |
| Cancer¶ | |||||
| Prior to HCT | 27 (11.7) | 13 (11.6) | 8 (12.7) | 1 (4) | 5 (16.1) |
| Leukemia | 7 (3) | 5 (4.5) | 1 (1.6) | 0 | 1 (3.2) |
| Solid tumor# | 20 (8.7) | 8 (7.1) | 7 (11.1) | 1 (4) | 4 (12.9) |
| Following HCT | 5 (7.1) | 0 | 2 (7.4) | 3 (20) | 0 |
See Table 2 for abbreviation definitions.
The diagnosis was established postmortem for 24 patients: they were not included in the calculation of age at diagnosis.
Severe: transfusion dependency, and/or androgen treatment, and/or blood count: ANC <500/mm3, platelets <20 000/mm3, and/or Hb <8.0 g/dL. BMF was always considered severe if HCT had been performed, and/or MDS or leukemia had been diagnosed.
Definition of severe liver disease: portal hypertension and/or liver cirrhosis/fibrosis.
One reported in the context of severe gut GvHD. One adult patient reported to have pyloric stenosis several years after HCT. Three patients had esophageal strictures mentioned in medical reports following HCT without specifying a GvHD diagnosis.
Two reported previous steroid treatment over several years (unknown dose). One patient received immunosuppression for lung transplant before developing hip avascular osteonecrosis. Not listed: 1 patient had osteonecrosis of the mandible following radiotherapy for head and neck squamous cell carcinoma.
Excluding 13 patients diagnosed with nonmelanoma skin cancer (squamous cell carcinoma or basal cell carcinoma), 1 following HCT.
Cancer cases included 11 head and neck cancers, 3 esophageal cancers, 3 anal/rectal cancers, 3 non-Hodgin lymphomas, 1 endometroid cancer, 1 cervical cancer. Two patients reported the occurrence of more than 1 solid tumor entity.