Table 1.
Clinical characteristics and outcomes of 1256 children with KMT2A-r AML and stratified by fusion-based group
| Total | 9p22/KMT2A::MLLT3 | 10p12/KMT2A::MLLT10 | 6q27/ KMT2A::AFDN | 19p13.1/KMT2A::ELL | 19p13.3/KMT2A::MLLT1 | 1q21/KMT2A::MLLT11 | 10p11.2/KMT2A::ABI1 | |
|---|---|---|---|---|---|---|---|---|
| No. (%) | 1256 (100) | 544 (43.3) | 218 (17.4) | 92 (7.3) | 75 (6.0) | 56 (4.5) | 28 (2.2) | 24 (1.9) |
| Sex, no. (%) (n = 1235) | ||||||||
| Male | 638 (51.7) | 276 (51.9) | 127 (58.5) | 44 (47.8) | 39 (52.7) | 30 (54.5) | 9 (32.1) | 14 (63.6) |
| Female | 597 (48.3) | 256 (48.1) | 90 (41.5) | 48 (52.2) | 35 (47.3) | 25 (45.5) | 19 (67.9) | 8 (36.4) |
| Age at diagnosis, y (n = 1256) | ||||||||
| Median (IQR) | 2.5 (1.0-10.0) | 3.0 (1.1-9.1) | 1.6 (0.7-7.7) | 10.5 (5.4-15.2) | 3.6 (0.6-12.3) | 6.8 (1.6-13.2) | 1.2 (0.5-3.0) | 1.5 (0.9-5.1) |
| WBC count, ×109/L, (n = 1186) | ||||||||
| Median (IQR) | 21.4 (5.7-87.8) | 12.3 (4.4-74.2) | 15.1 (5.2-57.7) | 65.8 (20.4-120.8) | 33.2 (11.0-93.7) | 28.1 (12.1-92.3) | 30.4 (9.0-63.0) | 30.9 (7.5-45.9) |
| CNS involvement, No. (%) (n = 722) | ||||||||
| Negative | 574 (79.5) | 274 (83.3) | 105 (80.8) | 41 (83.7) | 25 (69.4) | 19 (65.5) | 12 (80) | 7 (63.6) |
| Positive | 148 (20.5) | 55 (16.7) | 25 (19.2) | 8 (16.3) | 11 (30.6) | 10 (34.5) | 3 (20) | 4 (36.4) |
| FAB-type, no. (%) (n = 866) | ||||||||
| FAB-M0 | 18 (2.1) | 7 (1.8) | 0 (0) | 3 (5.2) | 0 (0) | 2 (6.1) | 1 (5.3) | 0 (0) |
| FAB-M1 | 33 (3.8) | 9 (2.3) | 1 (0.7) | 12 (20.7) | 3 (6.5) | 0 (0) | 1 (5.3) | 0 (0) |
| FAB-M2 | 19 (2.2) | 6 (1.5) | 1 (0.7) | 1 (1.7) | 4 (8.7) | 1 (3.0) | 4 (21.1) | 0 (0) |
| FAB-M4 | 121 (14.0) | 29 (7.4) | 11 (7.2) | 15 (25.9) | 17 (37.0) | 6 (18.2) | 9 (47.4) | 1 (6.7) |
| FAB-M5 | 619 (71.5) | 308 (78.6) | 132 (86.3) | 26 (44.8) | 20 (43.5) | 22 (66.7) | 3 (15.8) | 13 (86.7) |
| FAB-M7 | 31 (3.6) | 21 (5.4) | 6 (3.9) | 0 (0) | 0 (0) | 2 (6.1) | 0 (0) | 0 (0) |
| FAB unspecified | 25 (2.9) | 12 (3.1) | 2 (1.3) | 1 (1.7) | 2 (4.3) | 0 (0) | 1 (5.3) | 1 (6.7) |
| ACA, no. (%) (n = 1200) | ||||||||
| No | 638 (53.2) | 271 (52.5) | 100 (47.6) | 60 (67.4) | 44 (61.1) | 26 (47.3) | 20 (71.4) | 14 (58.3) |
| Yes | 562 (46.8) | 245 (47.5) | 110 (52.4) | 29 (32.6) | 28 (38.9) | 29 (52.7) | 8 (28.6) | 10 (41.7) |
| ACA type, no. (%) (n = 562) | ||||||||
| Structural | 159 (28.3) | 53 (21.6) | 44 (40.0) | 6 (20.7) | 4 (14.3) | 9 (31.0) | 3 (37.5) | 7 (70) |
| Numerical | 211 (37.5) | 110 (44.9) | 30 (27.3) | 9 (31.0) | 11 (39.3) | 11 (37.9) | 2 (25) | 2 (20) |
| Both∗ | 192 (34.2) | 82 (33.5) | 36 (32.7) | 14 (48.3) | 13 (46.4) | 9 (31.0) | 3 (37.5) | 1 (10) |
| CR, no. (%) (n = 1219) | 1066 (87.5) | 464 (89.9) | 187 (87.8) | 77 (85.6) | 62 (87.3) | 50 (90.9) | 22 (81.5) | 22 (91.7) |
| Clinical outcome | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 5-y pEFS | 1199 | 44.8 (41.9-47.7) | 512 | 54.0 (49.5-58.5) | 212 | 33.4 (26.7-40.1) | 89 | 23.3 (14.3-32.3) | 71 | 44.8 (33.0-56.6) | 55 | 34.7 (21.6-47.8) | 27 | 55.0 (36.0-74.0) | 24 | 21.8 (4.9-38.7) |
| 5-y pCIR | 1057 | 44.8 (41.7-47.9) | 459 | 36.2 (31.6-40.7) | 186 | 57.4 (49.6-64.4) | 77 | 66.3 (54.0-76.0) | 61 | 41.9 (29.2-54.2) | 50 | 54.1 (39.1-66.9) | 22 | 27.9 (10.9-47.9) | 22 | 71.4 (45.4-86.6) |
| 5-y pOS | 1217 | 62.6 (59.9-65.3) | 522 | 70.2 (66.1-74.3) | 214 | 54.0 (47.1-60.9) | 90 | 39.0 (27.8-50.2) | 72 | 67.8 (56.6-79.0) | 55 | 51.7 (37.6-65.8) | 27 | 73.3 (56.3-90.4) | 24 | 50.9 (29.9-71.9) |
| 19p13 | Xq24/KMT2A::SEPT6 | 17q21 | 1p32/KMT2A::EPS15 | 4q21/KMT2A::AFF1 | 17q12 | Other | P value | |
|---|---|---|---|---|---|---|---|---|
| No. (%) | 23 (1.8) | 22 (1.8) | 13 (1.0) | 13 (1.0) | 12 (1.0) | 10 (0.8) | 126 (10.0) | |
| Sex, no. (%) (n = 1235) | ||||||||
| Male | 8 (38.1) | 9 (42.9) | 7 (53.8) | 8 (61.5) | 5 (41.7) | 6 (60) | 56 (44.8) | .24 |
| Female | 13 (61.9) | 12 (57.1) | 6 (46.2) | 5 (38.5) | 7 (58.3) | 4 (40) | 69 (55.2) | |
| Age at diagnosis, y (n = 1256) | ||||||||
| Median (IQR) | 9.2 (1.0-13.0) | 1.4 (0.9-5.7) | 1.0 (0.3-3.8) | 0.6 (0.3-1.6) | 0.6 (0.1-1.9) | 1.7 (0.6-13.9) | 1.5 (0.6-7.7) | <.01 |
| WBC count, ×109/L, (n = 1186) | ||||||||
| Median (IQR) | 50.8 (11.4-103.0) | 18.0 (5.4-48.1) | 39.2 (8.4-127.4) | 39.4 (13.5-56.9) | 114.3 (24.3-401.0) | 41.0 (8.8-102.3) | 30.0 (8.2-145.8) | <.01 |
| CNS involvement, no. (%) (n = 722) | ||||||||
| Negative | 17 (94.4) | 9 (75) | 8 (72.7) | 8 (80) | 4 (66.7) | 3 (75) | 42 (67.7) | .10 |
| Positive | 1 (5.6) | 3 (25) | 3 (27.3) | 2 (20) | 2 (33.3) | 1 (25) | 20 (32.3) | |
| FAB-type, no. (%) (n = 866) | ||||||||
| FAB-M0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (11.1) | 0 (0) | 4 (4.5) | <.01 |
| FAB-M1 | 0 (0) | 2 (15.4) | 0 (0) | 0 (0) | 2 (22.2) | 0 (0) | 3 (3.4) | |
| FAB-M2 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (16.7) | 1 (1.1) | |
| FAB-M4 | 4 (28.6) | 3 (23.1) | 6 (60) | 1 (11.1) | 0 (0) | 2 (33.3) | 17 (19.1) | |
| FAB-M5 | 10 (71.4) | 8 (61.5) | 4 (40) | 8 (88.9) | 4 (44.4) | 3 (50) | 58 (65.2) | |
| FAB-M7 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 2 (2.2) | |
| FAB unspecified | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 2 (22.2) | 0 (0) | 4 (4.5) | |
| ACA, no. (%) (n = 1200) | ||||||||
| No | 12 (52.2) | 16 (72.7) | 5 (45.5) | 7 (53.8) | 3 (25) | 4 (40) | 56 (48.7) | .02 |
| Yes | 11 (47.8) | 6 (27.3) | 6 (54.5) | 6 (46.2) | 9 (75) | 6 (60) | 59 (51.3) | |
| ACA type, no. (%) (n = 562) | ||||||||
| Structural | 0 (0) | 0 (0) | 0 (0) | 3 (50) | 3 (33.3) | 2 (33.3) | 25 (42.4) | <.01 |
| Numerical | 7 (63.6) | 4 (66.7) | 5 (83.3) | 2 (33.3) | 2 (22.2) | 3 (50) | 13 (22.0) | |
| Both∗ | 4 (36.4) | 2 (33.3) | 1 (16.7) | 1 (16.7) | 4 (44.4) | 1 (16.7) | 21 (35.6) | |
| CR, no. (%) (n = 1219) | 20 (95.2) | 21 (100) | 12 (92.3) | 10 (83.3) | 6 (50) | 9 (90) | 104 (85.2) | .02 |
| Clinical outcome | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) | No. | % (95% CI) | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 5-y pEFS | 20 | 41.8 (18.9-64.7) | 21 | 76.2 (58.0-94.4) | 12 | 66.7 (40.0-93.4) | 12 | 75.0 (50.5-99.5) | 12 | 25.0 (0.5-49.5) | 10 | 56.3 (24.0-88.6) | 122 | 39.9 (30.9-48.9) | <.01 |
| 5-y pCIR | 19 | 43.4 (20.1-64.8) | 21 | 19.0 (5.7-38.3) | 11 | 9.1 (0.4-35.0) | 10 | 10.0 (0.5-37.4) | 6 | 50.0 (7.7-82.9) | 9 | 37.5 (7.2-69.4) | 104 | 52.2 (41.8-61.7) | <.01 |
| 5-y pOS | 20 | 62.4 (39.9-84.9) | 21 | 90.5 (78.0-100) | 13 | 69.2 (44.1-94.3) | 13 | 92.3 (78.0-100) | 12 | 25.0 (0.5-49.5) | 10 | 50.0 (13.5-86.5) | 124 | 60.8 (52.0-69.6) | <.01 |
Values in boldface indicate statistical significance. Fusion-based groups are displayed in descending order of occurrence. 9p22/KMT2A::MLLT3 refers to t(9;11)(p22;q23), 10p12/KMT2A::MLLT10 to t(10;11)(p12;q23), 6q27/KMT2A::AFDN to t(6;11)(q27;q23), 19p13 to t(11;19)(q23;p13) without ascertained subband, 19p13.1/KMT2A::ELL to t(11;19)(q23;p13.1), 19p13.3/KMT2A::MLLT1 to t(11;19)(q23;p13.3), 1q21/KMT2A::MLLT11 to t(1;11)(q21;q23), 10p11.2/KMT2A::ABI1 to t(10;11)(p11.2;q23), Xq24/KMT2A::SEPT6 to t(X;11)(q24;q23), 17q21 to t(11;17)(q23;q21), 4q21/KMT2A::AFF1 to t(4;11)(q21;q23), 1p32/KMT2A::EPS15 to t(1;11)(p32;q23), and 17q12 to t(11;17)(q23;q12).
CNS, central nervous system; No., number of patients; pCIR, probability of CIR; pEFS, probability of EFS; pOS, probability of OS.
∗
Including patients who had separate numerical and structural aberrations, as well as patients with gain of a chromosome with a structural aberration, for example, +der(9p) and +i(8q).