Table 2.
Clinical and cytogenetic characteristics by germline mutation status among 47 sequenced subjects*
| No mutation (n=37)** | BRCA1 or BRCA2 (n=5) | TP53 (n=3) | PALB2 (n=1) | CHEK2 (n=1) | |
|---|---|---|---|---|---|
| Age at primary diagnosis (years; range) | 53 (31–79) | 50 (33–53) | 23 (23–24) | 51 | 42 |
|
| |||||
| Latency (median in months; range) | 53 (11–792) | 133 (30–408) | 48 (30–81) | 90 | 21 |
|
| |||||
| Therapy-related leukemia type | |||||
| t-MN | 35 (95) | 5 (100) | 1 (33) | 1 (100) | 1 (100) |
| t-ALL | 2 (5) | 0 | 2 (67) | 0 | 0 |
|
| |||||
| Cytogenetics (n; %) | |||||
| Normal karyotype | 4 (11) | 2 (40) | 0 | 0 | 0 |
| Clonal abnormality | 30 (81) | 3 (60) | 3 (100) | 1 (100) | 1 (100)^ |
| Balanced translocations# | 14 (38) | 1 (20) | 1 (33) | 0 | 1 (100)^ |
| Chr 5 and/or 7 abn***# | 15 (41) | 2 (40) | 1 (33) | 1 (100) | 0 |
| Complex*** | 11 (30) | 1 (20) | 3 (100) | 1 (100) | 0 |
| Unknown | 3 (8) | 0 | 0 | 0 | 0 |
|
| |||||
| Survival from TRL diagnosis (median in months; IQR) | 13 (7–27) | 14 | 29 | 14 | 52 |
Tissue sources used for sequencing included: LBLs (n=24), buccal swabs (n=8), PB or BM in remission (n=6), skin fibroblasts (n=1), and PB or BM samples with leukemia (n= 8).
1 patient’s age at diagnosis and latency were unknown.
Patient had FISH studies only.
2 subjects had both a balanced translocation (t(15;17) and t(9;22)) and an abnormality of chromosome 5 and/or 7.
Complex karyotype as defined in ref 33. 11 of 15 subjects with chromosome 5 and/or 7 abnormalities with no inherited mutation had a complex karyotype as well as 1 of 2 subjects with BRCA1/BRCA2, 1 subject with a TP53, and the 1 subject with a PALB2 mutation.
Abbreviations: IQR=interquartile range; abn=abnormalities; TRL=therapy-related leukemia; t-MN=therapy-related myeloid neoplasm; t-ALL=therapy-related acute lymphoblastic leukemia; chr=chromosome