Comparison of genomic instability and other clinical features in single-hit and multi-hit TP53-mutated therapy-related myeloid neoplasms
| Variables . | Multi-hit (n = 102) . | Single-hit (n = 21) . | P value . |
|---|---|---|---|
| Age at t-MN diagnosis, y, median (IQR) | 67.5 (61.3, 74.0) | 67.0 (61.0, 72.0) | .664 |
| Female/Male | 46/56 | 7/14 | .346 |
| Hemoglobin, g/L, median (IQR) | 91.0 (81.0, 105.0) | 87.0 (80.3, 102.0) | .585 |
| WBC ×109/L, median (IQR) | 2.9 (1.9, 4.2) | 2.7 (2.2, 5.3) | .586 |
| ANC ×109/L, median (IQR) | 0.9 (0.5, 1.9) | 1.2 (0.3, 1.8) | .91 |
| Platelets ×109/L, median (IQR) | 54.5 (30.0, 92.5) | 35.0 (25.5, 64.5) | .196 |
| BM blasts %, median (IQR) | 6.0 (2.0, 22.0) | 4.0 (2.0, 29.0) | .88 |
| t-MN phenotype | |||
| t-MDS | 72 (70.6) | 14 (66.7) | .795 |
| t-AML | 30 (29.4) | 7 (33.3) | |
| Cytogenetic changes | |||
| Any cytogenetic aberrancies | 101 (99.0) | 20 (95.2) | .313 |
| Complex karyotype, n (%) | 91 (89.2) | 18 (85.7) | .706 |
| Monosomal karyotype, n (%) | 85 (83.3) | 16 (76.2) | .531 |
| Marker chromosome, n (%) | 59 (57.8) | 9 (42.9) | .235 |
| Ring chromosome, n (%) | 21 (20.6) | 4 (19.0) | 1 |
| Abnormal Chrom 17, n (%) | 31 (30.4) | 10 (47.6) | .136 |
| Abnormal Chrom 5, n (%) | 83 (81.4) | 14 (66.7) | .148 |
| Abnormal Chrom 7, n (%) | 61 (59.8) | 14 (66.7) | .63 |
| Abnormal Chrom 3, n (%) | 33 (32.4) | 4 (19.0) | .3 |
| Trisomy 8, n (%) | 20 (19.6) | 5 (23.8) | .766 |
| Abnormal Chrom 9, n (%) | 21 (20.6) | 4 (19.0) | 1 |
| Abnormal Chrom 11, n (%) | 27 (26.5) | 5 (23.8) | 1 |
| Abnormal Chrom 12, n (%) | 37 (36.3) | 6 (28.6) | .619 |
| Abnormal Chrom 13, n (%) | 36 (35.3) | 6 (28.6) | .622 |
| Abnormal Chrom 16, n (%) | 26 (25.5) | 3 (14.3) | .399 |
| Abnormal Chrom 18, n (%) | 34 (33.3) | 8 (38.1) | .801 |
| Abnormal Chrom 19, n (%) | 27 (26.5) | 7 (33.3) | .594 |
| Abnormal Chrom 20, n (%) | 24 (23.5) | 5 (23.8) | 1 |
| Abnormal Chrom 21, n (%) | 34 (33.3) | 5 (23.8) | .451 |
| Somatic mutations on NGS | |||
| TP53mut VAF, median (IQR) | 42.0 (31.6, 69.0) | 37.70 (20.0, 43.0) | .03 |
| Co-mutations (excluding TP53mut) | |||
| ≥ 2 mutations, n (%) | 18 (17.6) | 7 (33.3) | .06 |
| 1 mutation, n (%) | 26 (25.5) | 8 (38.1) | |
| No mutations, n (%) | 58 (56.9) | 6 (28.6) | |
| ASXL1, n (%) | 7 (6.9) | 3 (14.3) | .372 |
| RAS, n (%) | 2 (2.0) | 2 (9.5) | .135 |
| RUNX1, n (%) | 5 (4.9) | 1 (4.8) | 1 |
| SF3B1, n (%) | 2 (2.0) | 0 (0.0) | 1 |
| SRSF2, n (%) | 4 (3.9) | 2 (9.5) | .272 |
| TET2, n (%) | 7 (6.9) | 2 (9.5) | .65 |
| DNMT3A, n (%) | 11 (10.8) | 5 (23.8) | .148 |
| FLT3, n (%) | 0 (0.0) | 1 (4.8) | .171 |
| IDH2, n (%) | 1 (1.0) | 0 (0.0) | 1 |
| Disease-modifying therapy for t-MN∗ | |||
| No DMT, n (%) | 20 (19.6) | 6 (28.6) | .17 |
| Intensive chemotherapy, n (%) | 14 (13.7) | 4 (19.0) | |
| HMA-based chemotherapy, n (%) | 43 (42.2) | 9 (42.9) | |
| Venetoclax-based therapy, n (%) | 24 (23.5) | 1 (4.8) | |
| Unknown, n (%) | 1 (1) | 1 (4.8) | |
| Allogeneic SCT, n (%) | 16 (15.7) | 3 (14.3) | 1 |
| Months between primary to t-MN, median (IQR) | 103.4 (48.2, 165.5) | 79.4 (43.9, 151.9) | .685 |
| Clinical features at primary disease | |||
| Age at primary disease, y, median (IQR) | 57.0 (49.5, 65.0) | 55.5 (48.3, 60.8) | .464 |
| Hematologic malignancy, n (%) | 61 (59.8) | 14 (66.7) | .777 |
| Solid cancer, n (%) | 34 (33.3) | 7 (33.3) | |
| Other, n (%) | 7 (6.9) | 0 (0.0) | |
| Treatment for primary cancer/disease† | |||
| Chemotherapy alone for primary cancer/disease, n (%) | 53 (52%) | 9 (42.8%) | .603 |
| Chemotherapy plus radiotherapy for primary cancer, n (%) | 35 (34.3%) | 9 (42.8%) | .621 |
| Radiation only for primary cancer, n (%) | 8 (7.8%) | 3 (14.4%) | .602 |
| Immunosuppression, n (%) | 12 (11.8) | 0 (0.0) | .217 |
| Auto SCT for primary cancer, n (%) | 26 (25.5) | 6 (28.6) | .788 |
| Variables . | Multi-hit (n = 102) . | Single-hit (n = 21) . | P value . |
|---|---|---|---|
| Age at t-MN diagnosis, y, median (IQR) | 67.5 (61.3, 74.0) | 67.0 (61.0, 72.0) | .664 |
| Female/Male | 46/56 | 7/14 | .346 |
| Hemoglobin, g/L, median (IQR) | 91.0 (81.0, 105.0) | 87.0 (80.3, 102.0) | .585 |
| WBC ×109/L, median (IQR) | 2.9 (1.9, 4.2) | 2.7 (2.2, 5.3) | .586 |
| ANC ×109/L, median (IQR) | 0.9 (0.5, 1.9) | 1.2 (0.3, 1.8) | .91 |
| Platelets ×109/L, median (IQR) | 54.5 (30.0, 92.5) | 35.0 (25.5, 64.5) | .196 |
| BM blasts %, median (IQR) | 6.0 (2.0, 22.0) | 4.0 (2.0, 29.0) | .88 |
| t-MN phenotype | |||
| t-MDS | 72 (70.6) | 14 (66.7) | .795 |
| t-AML | 30 (29.4) | 7 (33.3) | |
| Cytogenetic changes | |||
| Any cytogenetic aberrancies | 101 (99.0) | 20 (95.2) | .313 |
| Complex karyotype, n (%) | 91 (89.2) | 18 (85.7) | .706 |
| Monosomal karyotype, n (%) | 85 (83.3) | 16 (76.2) | .531 |
| Marker chromosome, n (%) | 59 (57.8) | 9 (42.9) | .235 |
| Ring chromosome, n (%) | 21 (20.6) | 4 (19.0) | 1 |
| Abnormal Chrom 17, n (%) | 31 (30.4) | 10 (47.6) | .136 |
| Abnormal Chrom 5, n (%) | 83 (81.4) | 14 (66.7) | .148 |
| Abnormal Chrom 7, n (%) | 61 (59.8) | 14 (66.7) | .63 |
| Abnormal Chrom 3, n (%) | 33 (32.4) | 4 (19.0) | .3 |
| Trisomy 8, n (%) | 20 (19.6) | 5 (23.8) | .766 |
| Abnormal Chrom 9, n (%) | 21 (20.6) | 4 (19.0) | 1 |
| Abnormal Chrom 11, n (%) | 27 (26.5) | 5 (23.8) | 1 |
| Abnormal Chrom 12, n (%) | 37 (36.3) | 6 (28.6) | .619 |
| Abnormal Chrom 13, n (%) | 36 (35.3) | 6 (28.6) | .622 |
| Abnormal Chrom 16, n (%) | 26 (25.5) | 3 (14.3) | .399 |
| Abnormal Chrom 18, n (%) | 34 (33.3) | 8 (38.1) | .801 |
| Abnormal Chrom 19, n (%) | 27 (26.5) | 7 (33.3) | .594 |
| Abnormal Chrom 20, n (%) | 24 (23.5) | 5 (23.8) | 1 |
| Abnormal Chrom 21, n (%) | 34 (33.3) | 5 (23.8) | .451 |
| Somatic mutations on NGS | |||
| TP53mut VAF, median (IQR) | 42.0 (31.6, 69.0) | 37.70 (20.0, 43.0) | .03 |
| Co-mutations (excluding TP53mut) | |||
| ≥ 2 mutations, n (%) | 18 (17.6) | 7 (33.3) | .06 |
| 1 mutation, n (%) | 26 (25.5) | 8 (38.1) | |
| No mutations, n (%) | 58 (56.9) | 6 (28.6) | |
| ASXL1, n (%) | 7 (6.9) | 3 (14.3) | .372 |
| RAS, n (%) | 2 (2.0) | 2 (9.5) | .135 |
| RUNX1, n (%) | 5 (4.9) | 1 (4.8) | 1 |
| SF3B1, n (%) | 2 (2.0) | 0 (0.0) | 1 |
| SRSF2, n (%) | 4 (3.9) | 2 (9.5) | .272 |
| TET2, n (%) | 7 (6.9) | 2 (9.5) | .65 |
| DNMT3A, n (%) | 11 (10.8) | 5 (23.8) | .148 |
| FLT3, n (%) | 0 (0.0) | 1 (4.8) | .171 |
| IDH2, n (%) | 1 (1.0) | 0 (0.0) | 1 |
| Disease-modifying therapy for t-MN∗ | |||
| No DMT, n (%) | 20 (19.6) | 6 (28.6) | .17 |
| Intensive chemotherapy, n (%) | 14 (13.7) | 4 (19.0) | |
| HMA-based chemotherapy, n (%) | 43 (42.2) | 9 (42.9) | |
| Venetoclax-based therapy, n (%) | 24 (23.5) | 1 (4.8) | |
| Unknown, n (%) | 1 (1) | 1 (4.8) | |
| Allogeneic SCT, n (%) | 16 (15.7) | 3 (14.3) | 1 |
| Months between primary to t-MN, median (IQR) | 103.4 (48.2, 165.5) | 79.4 (43.9, 151.9) | .685 |
| Clinical features at primary disease | |||
| Age at primary disease, y, median (IQR) | 57.0 (49.5, 65.0) | 55.5 (48.3, 60.8) | .464 |
| Hematologic malignancy, n (%) | 61 (59.8) | 14 (66.7) | .777 |
| Solid cancer, n (%) | 34 (33.3) | 7 (33.3) | |
| Other, n (%) | 7 (6.9) | 0 (0.0) | |
| Treatment for primary cancer/disease† | |||
| Chemotherapy alone for primary cancer/disease, n (%) | 53 (52%) | 9 (42.8%) | .603 |
| Chemotherapy plus radiotherapy for primary cancer, n (%) | 35 (34.3%) | 9 (42.8%) | .621 |
| Radiation only for primary cancer, n (%) | 8 (7.8%) | 3 (14.4%) | .602 |
| Immunosuppression, n (%) | 12 (11.8) | 0 (0.0) | .217 |
| Auto SCT for primary cancer, n (%) | 26 (25.5) | 6 (28.6) | .788 |
ANC, absolute neutrophil count; Chrom, chromosome; DMT, disease modifying therapy; HMA, hypomethylating agents; IQR, interquartile range; NGS, next-generation sequencing; SCT, stem cell transplant; WBC, white blood count.
First line of therapy only.
Six patients with muti-hit did not receive chemotherapy and/or radiotherapy. They had only immunosuppression.