Clinical and biological variables in previously treated CLL patients with partial or complete TP53 disruption
| . | Total . | Heterozygous TP53mut (subgroup 2) . | Hemizygous del17p (subgroup 3) . | TP53mut/del17p (subgroup 4) . | TP53DN/ >1 TP53mut (subgroup 5) . | P* . |
|---|---|---|---|---|---|---|
| No. of patients, n | 61 | 16 | 9 | 28 | 8 | |
| Sex, n | 61 | 16 | 9 | 28 | 8 | .65 |
| Female | 22 (36%) | 4 (25%) | 3 (33%) | 11 (40%) | 4 (50%) | |
| Male | 39 (64%) | 12 (75%) | 6 (67%) | 17 (60%) | 4 (50%) | |
| Age, n | 61 | 16 | 9 | 28 | 8 | .37 |
| Mean (SD) | 62.5 (8.4) | 65.2 (10.0) | 59.9 (8.1) | 61.5 (7.4) | 63.2 (8.2) | |
| Median (range) | 62 (44-81) | 66.5 (44-81) | 58 (48-73) | 61 (47-76) | 67.5 (51-71) | |
| Binet stage, n | 61 | 16 | 9 | 28 | 8 | .61 |
| A or B | 40 (66%) | 10 (62.5%) | 6 (67%) | 17 (61%) | 7 (87.5%) | |
| C | 21 (34%) | 6 (37.5%) | 3 (33%) | 11 (40%) | 1 (12.5%) | |
| β2 microglobulin, mg/L, n | 60 | 16 | 9 | 27 | 8 | .77 |
| Mean (SD) | 4.6 (2.5) | 4.5 (2.3) | 5.3 (2.9) | 4.6 (2.8) | 3.8 (1.3) | |
| Median (range) | 3.7 (1.5-13.6) | 3.7 (1.9-8.8) | 4.4 (1.5-9.7) | 3.7 (1.6-13.6) | 3.5 (1.7-5.8) | |
| Lymphocytes, 109/L, n | 61 | 16 | 9 | 28 | 8 | .23 |
| Mean (SD) | 68.5 (68.3) | 61.3 (46.7) | 51.8 (78.4) | 83.7 (80.5) | 48.5 (38.1) | |
| Median (range) | 49.2 (0.9-333) | 62.7 (0.9-180) | 17.8 (3.8-244) | 69.0 (8.2-333) | 40.7(6.4-101) | |
| B symptoms, n | 61 | 16 | 9 | 28 | 8 | .92 |
| No | 44 (72%) | 11 (69%) | 6 (67%) | 21 (75%) | 6 (75%) | |
| Yes | 17 (28%) | 5 (31%) | 3 (33%) | 7 (25%) | 2 (25%) | |
| ECOG performance status, n | 61 | 16 | 9 | 28 | 8 | .83 |
| 0 | 31 (51%) | 7 (44%) | 4 (44%) | 15 (54%) | 5 (62.5%) | |
| 1 | 30 (49%) | 9 (56%) | 5 (56%) | 13 (46%) | 3 (37.5%) | |
| IGVH mutational status, n | 61 | 16 | 9 | 28 | 8 | .03 |
| Mutated | 21 (34%) | 7 (44%) | 2 (22%) | 6 (21%) | 6 (75%) | |
| Unmutated | 40 (66%) | 9 (56%) | 7 (78%) | 22 (79%) | 2 (25%) | |
| ZAP70, n | 51 | 12 | 9 | 24 | 6 | .08 |
| Negative | 27 (53%) | 6 (50%) | 5 (56%) | 10 (42%) | 6 (100%) | |
| Positive | 24 (47%) | 6 (50%) | 4 (44%) | 14 (58%) | 0 (0%) | |
| CD38, n | 44 | 11 | 7 | 20 | 6 | .63 |
| Negative | 19 (43%) | 5 (45.5%) | 3 (43%) | 7 (35%) | 4 (67%) | |
| Positive | 25 (57%) | 6 (54.5%) | 4 (57%) | 13 (65%) | 2 (33%) | |
| Del(11q), n | 61 | 16 | 9 | 28 | 8 | .42 |
| No | 55 (90%) | 15 (94%) | 9 (100%) | 23 (82%) | 8 (100%) | |
| Yes | 6 (10%) | 1 (6%) | 0 (0%) | 5 (18%) | 0 (0%) | |
| Del(13q), n | 61 | 16 | 9 | 28 | 8 | .94 |
| No | 31 (51%) | 7 (44%) | 5 (56%) | 15 (54%) | 4 (50%) | |
| Yes | 30 (49%) | 9 (56%) | 4 (44%) | 13 (46%) | 4 (50%) | |
| Trisomy 12, n | 61 | 16 | 9 | 28 | 8 | .96 |
| No | 51 (84%) | 14 (87.5%) | 7 (78%) | 23 (82%) | 7 (87.5%) | |
| Yes | 10 (16%) | 2 (12.5%) | 2 (22%) | 5 (18%) | 1 (12.5%) | |
| Mean residual activity of TP53mut, n (%)† | 33 | 15 | NA | 18 | NA | .01 |
| Mean (SD) | 13.3 (21.0) | 24.3 (27.3) | NA | 4.1 (5.1) | NA | |
| Median (range) | 4.7 (0-73.1) | 12.5 (0-73) | NA | 1.2 (0-12.5) | NA | |
| Previous chemotherapy, n | 60 | 16 | 8 | 28 | 8 | .22 |
| Alkylator refractory | 24 (40%) | 3 (19%) | 4 (50%) | 15 (54%) | 2 (25%) | |
| Alkylator sensitive | 28 (47%) | 9 (56%) | 4 (50%) | 10 (36%) | 5 (62.5%) | |
| Fludarabine | 8 (13%) | 4 (25%) | 0 (0%) | 3 (11%) | 1 (12.5%) | |
| Treatment at second line | 61 | 16 | 9 | 28 | 8 | .3 |
| FCR | 30 (49%) | 9 (56%) | 2 (22%) | 14 (50%) | 5 (62.5%) | |
| FC | 31 (51%) | 7 (44%) | 7 (78%) | 14 (50%) | 3 (37.5%) | |
| Time from last progression (days), n | 61 | 16 | 9 | 28 | 8 | .56 |
| Mean (SD) | 134 (190) | 142 (213) | 186 (289) | 94 (103) | 200 (243) | |
| Median (Range) | 56 (2-929) | 63 (2-845) | 79 (16-929) | 47 (13-378) | 123.5 (10-770) |
| . | Total . | Heterozygous TP53mut (subgroup 2) . | Hemizygous del17p (subgroup 3) . | TP53mut/del17p (subgroup 4) . | TP53DN/ >1 TP53mut (subgroup 5) . | P* . |
|---|---|---|---|---|---|---|
| No. of patients, n | 61 | 16 | 9 | 28 | 8 | |
| Sex, n | 61 | 16 | 9 | 28 | 8 | .65 |
| Female | 22 (36%) | 4 (25%) | 3 (33%) | 11 (40%) | 4 (50%) | |
| Male | 39 (64%) | 12 (75%) | 6 (67%) | 17 (60%) | 4 (50%) | |
| Age, n | 61 | 16 | 9 | 28 | 8 | .37 |
| Mean (SD) | 62.5 (8.4) | 65.2 (10.0) | 59.9 (8.1) | 61.5 (7.4) | 63.2 (8.2) | |
| Median (range) | 62 (44-81) | 66.5 (44-81) | 58 (48-73) | 61 (47-76) | 67.5 (51-71) | |
| Binet stage, n | 61 | 16 | 9 | 28 | 8 | .61 |
| A or B | 40 (66%) | 10 (62.5%) | 6 (67%) | 17 (61%) | 7 (87.5%) | |
| C | 21 (34%) | 6 (37.5%) | 3 (33%) | 11 (40%) | 1 (12.5%) | |
| β2 microglobulin, mg/L, n | 60 | 16 | 9 | 27 | 8 | .77 |
| Mean (SD) | 4.6 (2.5) | 4.5 (2.3) | 5.3 (2.9) | 4.6 (2.8) | 3.8 (1.3) | |
| Median (range) | 3.7 (1.5-13.6) | 3.7 (1.9-8.8) | 4.4 (1.5-9.7) | 3.7 (1.6-13.6) | 3.5 (1.7-5.8) | |
| Lymphocytes, 109/L, n | 61 | 16 | 9 | 28 | 8 | .23 |
| Mean (SD) | 68.5 (68.3) | 61.3 (46.7) | 51.8 (78.4) | 83.7 (80.5) | 48.5 (38.1) | |
| Median (range) | 49.2 (0.9-333) | 62.7 (0.9-180) | 17.8 (3.8-244) | 69.0 (8.2-333) | 40.7(6.4-101) | |
| B symptoms, n | 61 | 16 | 9 | 28 | 8 | .92 |
| No | 44 (72%) | 11 (69%) | 6 (67%) | 21 (75%) | 6 (75%) | |
| Yes | 17 (28%) | 5 (31%) | 3 (33%) | 7 (25%) | 2 (25%) | |
| ECOG performance status, n | 61 | 16 | 9 | 28 | 8 | .83 |
| 0 | 31 (51%) | 7 (44%) | 4 (44%) | 15 (54%) | 5 (62.5%) | |
| 1 | 30 (49%) | 9 (56%) | 5 (56%) | 13 (46%) | 3 (37.5%) | |
| IGVH mutational status, n | 61 | 16 | 9 | 28 | 8 | .03 |
| Mutated | 21 (34%) | 7 (44%) | 2 (22%) | 6 (21%) | 6 (75%) | |
| Unmutated | 40 (66%) | 9 (56%) | 7 (78%) | 22 (79%) | 2 (25%) | |
| ZAP70, n | 51 | 12 | 9 | 24 | 6 | .08 |
| Negative | 27 (53%) | 6 (50%) | 5 (56%) | 10 (42%) | 6 (100%) | |
| Positive | 24 (47%) | 6 (50%) | 4 (44%) | 14 (58%) | 0 (0%) | |
| CD38, n | 44 | 11 | 7 | 20 | 6 | .63 |
| Negative | 19 (43%) | 5 (45.5%) | 3 (43%) | 7 (35%) | 4 (67%) | |
| Positive | 25 (57%) | 6 (54.5%) | 4 (57%) | 13 (65%) | 2 (33%) | |
| Del(11q), n | 61 | 16 | 9 | 28 | 8 | .42 |
| No | 55 (90%) | 15 (94%) | 9 (100%) | 23 (82%) | 8 (100%) | |
| Yes | 6 (10%) | 1 (6%) | 0 (0%) | 5 (18%) | 0 (0%) | |
| Del(13q), n | 61 | 16 | 9 | 28 | 8 | .94 |
| No | 31 (51%) | 7 (44%) | 5 (56%) | 15 (54%) | 4 (50%) | |
| Yes | 30 (49%) | 9 (56%) | 4 (44%) | 13 (46%) | 4 (50%) | |
| Trisomy 12, n | 61 | 16 | 9 | 28 | 8 | .96 |
| No | 51 (84%) | 14 (87.5%) | 7 (78%) | 23 (82%) | 7 (87.5%) | |
| Yes | 10 (16%) | 2 (12.5%) | 2 (22%) | 5 (18%) | 1 (12.5%) | |
| Mean residual activity of TP53mut, n (%)† | 33 | 15 | NA | 18 | NA | .01 |
| Mean (SD) | 13.3 (21.0) | 24.3 (27.3) | NA | 4.1 (5.1) | NA | |
| Median (range) | 4.7 (0-73.1) | 12.5 (0-73) | NA | 1.2 (0-12.5) | NA | |
| Previous chemotherapy, n | 60 | 16 | 8 | 28 | 8 | .22 |
| Alkylator refractory | 24 (40%) | 3 (19%) | 4 (50%) | 15 (54%) | 2 (25%) | |
| Alkylator sensitive | 28 (47%) | 9 (56%) | 4 (50%) | 10 (36%) | 5 (62.5%) | |
| Fludarabine | 8 (13%) | 4 (25%) | 0 (0%) | 3 (11%) | 1 (12.5%) | |
| Treatment at second line | 61 | 16 | 9 | 28 | 8 | .3 |
| FCR | 30 (49%) | 9 (56%) | 2 (22%) | 14 (50%) | 5 (62.5%) | |
| FC | 31 (51%) | 7 (44%) | 7 (78%) | 14 (50%) | 3 (37.5%) | |
| Time from last progression (days), n | 61 | 16 | 9 | 28 | 8 | .56 |
| Mean (SD) | 134 (190) | 142 (213) | 186 (289) | 94 (103) | 200 (243) | |
| Median (Range) | 56 (2-929) | 63 (2-845) | 79 (16-929) | 47 (13-378) | 123.5 (10-770) |
>1 TP53mut, patients with >1 TP53 mutation; NA, not applicable; TP53DN, patients with predicted dominant-negative TP53 mutations according to the IARC database.
*Association between TP53 partial/complete disruption and various clinical and biological variables applying the Kruskal-Wallis test or the Fisher exact test, respectively, for continuous and categorical variables.
†Predicted TP53 residual activity were retrieved from the 2007_R1 release of the UMD_TP53 Mutation database (http://p53.free.fr).