Table 1.
Comparisons of clinical and molecular features and the outcomes in overall patient cohort and within the ELN Intermediate I Genetic Group at presentation by MLL status
| Characteristic | MLL-PTD (n = 13) | MLL-WT (n = 213) | P-valuea |
|---|---|---|---|
| Age, y | 0.25 | ||
| Median | 65 | 68 | |
| Range | 60–77 | 60 – 83 | |
| Sex, no. (%) | 0.08 | ||
| Male | 10 (77) | 106 (50) | |
| Female | 3 (23) | 107 (50) | |
| Race, no. (%) | 0.61 | ||
| White | 13 (100) | 192 (91) | |
| Non-white | 0 (0) | 19 (9) | |
| Hemoglobin, g/dl | 0.01 | ||
| Median | 8.5 | 9.5 | |
| Range | 6.0 – 11.7 | 5.4 – 15.0 | |
| Platelet count, × 109/l | 0.41 | ||
| Median | 53 | 70 | |
| Range | 20 – 246 | 11 – 850 | |
| WBC count, × 109/l | 0.16 | ||
| Median | 9.1 | 28.4 | |
| Range | 1.3 –434.1 | 0.8 – 450.0 | |
| Blood blasts, % | 0.44 | ||
| Median | 32 | 52 | |
| Range | 0 – 96 | 0 – 99 | |
| Bone marrow blasts, % | 0.93 | ||
| Median | 47 | 68 | |
| Range | 17–97 | 4 – 97 | |
| FAB, no. (%)b | 0.68 | ||
| M0 | 0 (0) | 3 (2) | |
| M1 | 3 (33) | 32 (23) | |
| M2 | 1 (11) | 44 (31) | |
| M4 | 3 (33) | 31 (22) | |
| M5 | 2 (22) | 27 (19) | |
| M6 | 0 (0) | 3 (2) | |
| Extramedullary involvement, no. (%) | 2 (15) | 51 (25) | 0.74 |
| ELN Genetic Group, no. (%)c | 0.007 | ||
| Favorable | 1 (8) | 97 (47) | |
| Intermediate-I | 12 (92) | 109 (53) | |
| FLT3-ITD, no. (%) | 1.00 | ||
| Present | 4 (31) | 70 (34) | |
| Absent | 9 (69) | 137 (66) | |
| NPM1, no. (%) | 0.002 | ||
| Mutated | 2 (15) | 126 (61) | |
| Wild type | 11 (85) | 80 (39) | |
| CEBPA, no. (%) | 0.37 | ||
| Mutated | 0 (0) | 26 (13) | |
| Single mutated | 0 | 16 | |
| Double mutated | 0 | 10 | |
| Wild type | 13 (100) | 180 (87) | |
| RUNX1, no. (%) | 0.43 | ||
| Mutated | 3 (25) | 31 (16) | |
| Wild type | 9 (75) | 159 (84) | |
| WT1, no. (%) | 0.18 | ||
| Mutated | 2 (15) | 11 (5) | |
| Wild type | 11 (85) | 195 (95) | |
| FLT3-TKD, no. (%) | 1.00 | ||
| Present | 1 (8) | 22 (11) | |
| Absent | 12 (92) | 184 (89) | |
| IDH1, no. (%) | 1.00 | ||
| Mutated | 1 (8) | 25(12) | |
| Wild type | 12 (92) | 179 (88) | |
| IDH2, no. (%) | 0.51 | ||
| IDH2 | 4 (31) | 47 (23) | |
| R140 | 4 | 38 | |
| R172 | 0 | 9 | |
| Wild type | 9 (69) | 157 (77) | |
| TET2, no. (%) | 1.00 | ||
| Mutated | 3 (23) | 58 (29) | |
| Wild type | 10 (77) | 144 (71) | |
| ASXL1, no. (%) | 0.23 | ||
| Mutated | 4 (31) | 31 (15) | |
| Wild type | 9 (69) | 171 (85) | |
| DNMT3A | 1.00 | ||
| Mutated | 4 (33) | 65 (33) | (mut vs wt) |
| R882 | 3 | 38 | |
| Non-R882 | 1 | 27 | |
| Wild type | 8 (67) | 135 (67) | |
| ERG expression, no. (%)d | 0.47 | ||
| High | 3 (38) | 75 (54) | |
| Low | 5 (62) | 64 (46) | |
| BAALC expression, no. (%)d | 0.28 | ||
| High | 6 (75) | 69 (51) | |
| Low | 2 (25) | 66 (49) | |
| MN1 expression group, no. (%)d | 1.00 | ||
| High | 6 (55) | 69 (51) | |
| Low | 5 (45) | 67 (49) | |
| Complete remission rate, no. (%) | 9 (69) | 142 (67) | 1.00 |
| Disease-free survivale | 0.45 | ||
| Median, y | 0.7 | 0.8 | |
| Disease-free at 3 y, | 22 (3– 51) | 18 (12– 24) | |
| % (95% CI) | |||
| Overall survivalf | 0.38 | ||
| Median, y | 1.1 | 1.1 | |
| Alive at 3 y, % (95% CI) | 15 (2– 39) | 19 (14– 24) | |
| Event-free survival | 0.60 | ||
| Median, y | 0.6 | 0.6 | |
| Event-free at 3 y, | 15 (2– 39) | 12 (8– 16) | |
| % (95% CI) | |||
| ELN Intermediate-I Genetic Group | |||
| No. of patients | 12 | 109 | |
| Complete remission rate, no. (%) | 8 (67) | 62 (57) | 0.56 |
| Disease-free survivalg | 0.88 | ||
| Median, y | 0.6 | 0.6 | |
| Disease-free at 3 y, % (95% CI) | 13 (1– 42) | 10 (4– 19) | |
| Overall survivalh | 0.92 | ||
| Median, y | 1.0 | 0.8 | |
| Alive at 3 y, % (95% CI) | 8 (1– 31) | 10 (5– 17) | |
| Event-free survival | 0.88 | ||
| Median, y | 0.6 | 0.3 | |
| Event-free at 3 y, % (95% CI) | 8 (1– 31) | 6 (2– 11) |
Abbreviations: CI, confidence interval; ELN, European LeukemiaNet; FAB, French-American-British classification; FLT3-ITD, internal tandem duplication of the FLT3 gene; FLT3-TKD, tyrosine kinase domain mutation in the FLT3 gene; WBC, white blood cell.
P-values for categorical variables are from Fisher’s exact test, P-values for continuous variables are from Wilcoxon rank sum test and P-values for time to event variables are from the log-rank test.
FAB are centrally reviewed.
The ELN Favorable Genetic Group is defined as patients with mutated CEBPA or mutated NPM1 without FLT3-ITD; Intermediate-I Genetic Group is defined as patients that are not classified in the Favorable Genetic Group, that is, those with wild-type CEBPA who are either FLT3-ITD-positive with or without an NPM1 mutation or FLT3-ITD-negative with wild-type NPM1.
The median expression value was used as a cut point.
The median follow-up for those who have not had an event is 5.5 years, range: 4.6 – 11.6 years (n = 15).
The median follow-up for those alive is 5.5 years, range: 2.3 – 11.6 years (n = 19).
The median follow-up for those who have not had an event is 7.3 years, range: 5.5 – 7.4 years (n = 3).
The median follow-up for those alive is 7.3 years, range: 5.5 – 7.4 years (n = 3).