Table 1.
Pretreatment clinical and molecular characteristics and outcome of patients with de novo acute myeloid leukemia and sole +8 and comparison by age group (<60 years vs ≥60 years)
| Characteristic |
Sole +8
AML (n=80) |
Sole +8
AML <60 years (n=40) |
Sole +8
AML ≥60 years (n=40) |
P f |
|---|---|---|---|---|
|
| ||||
| Age, years | - | |||
| Median | 59 | 43 | 71 | |
| Range | 18-84 | 18-59 | 60-84 | |
|
| ||||
| Male sex, no. (%) | 50 (63) | 26 (65) | 24 (60) | 0.82 |
|
| ||||
| Race, no. (%) | 0.85 | |||
| White | 69 (87) | 35 (90) | 34 (85) | |
| Black or African American | 8 (10) | 3 (8) | 5 (13) | |
| Other | 2 (3) | 1 (2) | 1(2) | |
|
| ||||
| Hemoglobin, g/dL | 0.64 | |||
| Median | 9.2 | 9.2 | 9.1 | |
| Range | 5.0-15.8 | 5.0-15.8 | 5.3-14.1 | |
|
| ||||
| Platelet count, × 109/L | 0.63 | |||
| Median | 46 | 49 | 41 | |
| Range | 5-233 | 11-148 | 5-233 | |
|
| ||||
| WBC, × 109/L | 0.003 | |||
| Median | 8.9 | 20.7 | 4.2 | |
| Range | 0.6-302.3 | 0.6-302.3 | 0.8-187.0 | |
|
| ||||
| Blood blasts, % | 0.02 | |||
| Median | 38 | 49 | 23 | |
| Range | 0-97 | 2-97 | 0-91 | |
|
| ||||
| Bone marrow blasts, % | 0.14 | |||
| Median | 70 | 77 | 56 | |
| Range | 18-94 | 22-90 | 18-94 | |
|
| ||||
| FAB, no. (%) a | <0.001 (M1/M2 vs M4/M5) |
|||
| M0 | 3 (5) | 1 (3) | 2 (7) | |
| M1 | 9 (15) | 2 (6) | 7 (26) | |
| M2 | 17 (29) | 6 (19) | 11 (41) | |
| M4 | 9 (15) | 5 (16) | 4 (15) | |
| M5 | 19 (32) | 17 (53) | 2 (7) | |
| M6 | 2 (3) | 1 (3) | 1 (4) | |
|
| ||||
| Extramedullary involvement, no. (%) | 15 (20) | 9 (24) | 6 (16) | 0.57 |
| CNS | 0 (0) | 0 (0) | 0 (0) | NA |
| Hepatomegaly | 2 (3) | 2 (5) | 0 (0) | 0.24 |
| Splenomegaly | 3 (4) | 3 (8) | 0 (0) | 0.24 |
| Lymphadenopathy | 5 (7) | 4 (11) | 1 (3) | 0.19 |
| Skin infiltrates | 6 (8) | 1 (3) | 5 (14) | 0.11 |
| Gum hypertrophy | 6 (8) | 4 (11) | 2 (5) | 0.67 |
| Mediastinal mass | 1 (1) | 0 (0) | 1 (3) | 0.49 |
|
| ||||
| +8 metaphases in BM, no.
(%) ≥ 80% |
50 (63) | 26 (65) | 24 (60) | 0.82 |
|
| ||||
| RUNX1, no. (%) | 0.008 | |||
| Mutated | 25 (32) | 7 (18) | 18 (46) | |
| Wild-type | 54 (68) | 33 (82) | 21 (54) | |
|
| ||||
| ASXL1, no. (%) | 0.002 (mutated vs wild-type) |
|||
| Mutated | 22 (29) | 5 (13) | 17 (46) | |
| c.1934dupG | 10 | 1 | 9 | |
| Other | 12 | 4 | 8 | |
| Wild-type | 54 (71) | 34 (87) | 20 (54) | |
|
| ||||
| FLT3-ITD, no. (%) | 0.14 | |||
| Positive | 23 (29) | 15 (38) | 8 (20) | |
| Negative | 57 (71) | 25 (62) | 32 (80) | |
|
| ||||
| IDH2, no. (%) | 0.04 (mutated vs wild-type) |
|||
| Mutated | 21 (26) | 6 (15) | 15 (38) | |
| R140 mutated | 13 | 4 | 9 | |
| R172 mutated | 8 | 2 | 6 | |
| Wild-type | 59 (74) | 34 (85) | 25 (62) | |
|
| ||||
| DNMT3A, no. (%) | 0.58 (mutated vs wild-type) |
|||
| Mutated | 17 (25) | 8 (22) | 9 (29) | |
| R882 | 12 | 7 | 5 | |
| Non-R882 | 5 | 1 | 4 | |
| Wild-type | 51 (75) | 29 (78) | 22 (71) | |
|
| ||||
| NPM1, no. (%) | 0.18 | |||
| Mutated | 18 (22.5) | 12 (30) | 6 (15) | |
| Wild-type | 62 (77.5) | 28 (70) | 34 (85) | |
|
| ||||
| FLT3-TKD, no. (%) | 0.54 | |||
| Positive | 13 (17) | 5 (13) | 8 (21) | |
| Negative | 65 (83) | 34 (87) | 31 (79) | |
|
| ||||
| IDH1, no. (%) | 0.19 | |||
| Mutated | 11 (14) | 3 (8) | 8 (20) | |
| Wild-type | 69 (86) | 37 (92) | 32 (80) | |
|
| ||||
| RAS, no. (%) | 0.31 (mutated vs wild-type) |
|||
| Mutated | 10 (13) | 3 (8) | 7 (18) | |
| NRAS mutated | 9 | 3 | 6 | |
| KRAS mutated | 1 | 0 | 1 | |
| Wild-type | 70 (87) | 37 (92) | 33 (82) | |
|
| ||||
| TET2, no. (%) | 0.001 | |||
| Mutated | 8 (11) | 0 (0) | 8 (24) | |
| Wild-type | 64 (89) | 39 (100) | 25 (76) | |
|
| ||||
| CEBPA, no. (%) | 0.20 (mutated vs wild-type) |
|||
| Mutated | 6 (8) | 1 (3) | 5 (13) | |
| Single mutated | 4 | 1 | 3 | |
| Double mutated | 2 | 0 | 2 | |
| Wild-type | 74 (92) | 39 (97) | 35 (87) | |
|
| ||||
| WT1, no. (%) | 1.00 | |||
| Mutated | 3 (4) | 2 (5) | 1 (3) | |
| Wild-type | 77 (96) | 38 (95) | 39 (97) | |
|
| ||||
| BAALC expression, no. (%) b | 0.62 | |||
| High | 33 (50) | 16 (55) | 17 (46) | |
| Low | 33 (50) | 13 (45) | 20 (54) | |
|
| ||||
| miR-155 expression, no. (%) c | 1.00 | |||
| High | 31 (48) | 14 (48) | 17 (49) | |
| Low | 33 (52) | 15 (52) | 18 (51) | |
|
| ||||
| miR-3151 expression, no. (%) b | 1.00 | |||
| High | 21 (50) | 8 (50) | 13 (50) | |
| Low | 21 (50) | 8 (50) | 13 (50) | |
| Endpoint |
Sole +8
AML (n=59) d |
Sole +8
AML <60 years (n=30) |
Sole +8
AML ≥60 years (n=29) |
OR/HR
e
(95% CI) |
P f |
|---|---|---|---|---|---|
|
| |||||
| Complete remission | 0.68 (0.23-1.98) |
0.47 | |||
| No. in complete remission (%) | 38 (64) | 18 (60) | 20 (69) | ||
|
| |||||
| Disease-free survival | 0.59 (0.30-1.16) |
0.13 | |||
| No. of events | 36 | 16 | 20 | ||
| Median, years | 0.7 | 1.1 | 0.6 | ||
| % Disease-free at 3 years (95% CI) | 12 (4-25) | 21 (6-42) | 5 (0-21) | ||
| % Disease-free at 5 years (95% CI) | 9 (2-21) | 14 (3-35) | 5 (0-21) | ||
|
| |||||
| Overall survival | 0.67 (0.38-1.16) |
0.15 | |||
| No. of events | 52 | 24 | 28 | ||
| Median, years | 1.3 | 1.5 | 1.2 | ||
| % Alive at 3 years (95% CI) | 23 (13-35) | 29 (14-46) | 17 (6-33) | ||
| % Alive at 5 years (95% CI) | 15 (7-26) | 19 (7-36) | 10 (3-24) | ||
Abbreviations: WBC, white blood count; FAB, French-American-British classification; NA, not applicable; FLT3-ITD, internal tandem duplication of the FLT3 gene; FLT3-TKD, tyrosine kinase domain mutations of the FLT3 gene; OR, odds ratio; HR, hazard ratio; CI, confidence interval.
FAB morphology was centrally reviewed.
The median expression value was used as a cut point. It was calculated based on the expression levels assessed by RT-PCR.
The median expression value was used as a cut point. It was calculated based on the expression levels on the Affymetrix array.
Of the 80 patients, 59 were evaluable for outcome. Pretreatment clinical and molecular characteristics of the patients included in outcome analyses are provided in Supplementary Table S2.
Ratios are comparing outcome of patients <60 years vs ≥60 years.
P-values compare patients who are <60 years vs ≥60 years. For baseline continuous variables the Wilcoxon rank sum test was used, for baseline categorical variables the Fisher’s exact test was used. For CR, the Wald test was used from the logistic regression model. For overall and disease-free survival, the Wald test was used from the Cox regression models.