Clinical parameters of relapsed pediatric BCP-ALL patients with NT5C2 mutations
| Parameter/variable . | Total, n (%) . | NT5C2 wild-type, n (%) . | NT5C2 clonal mut, n (%) . | NT5C2 subclonal mut, n (%) . | P* . | P† . | P‡ . | P§ . |
|---|---|---|---|---|---|---|---|---|
| Total | 455 | 380 | 28 | 47 | ||||
| Sex | .348 | .156 | .323 | .531 | ||||
| Male | 263 (57.8) | 220 (57.9) | 13 (46.4) | 30 (63.8) | ||||
| Female | 192 (42.2) | 160 (42.1) | 15 (53.6) | 17 (36.2) | ||||
| Age at initial diagnosis (y), median (min-max) | 4.81 (0.06-22.05) | 4.83 (0.28-21.65) | 4.17 (1.15-20.18) | 5.49 (0.06-22.05) | .949 | .844 | .923 | .757 |
| Initial treatment protocol | .680 | 1.000 | .445 | .717 | ||||
| German ALL-BFM | 327 (72.5) | 275 (73.1) | 19 (67.9) | 33 (70.2) | ||||
| German COALL | 116 (25.7) | 95 (25.3) | 8 (28.6) | 13 (27.7) | ||||
| Other | 8 (1.8) | 6 (1.6) | 1 (3.6) | 1 (2.1) | ||||
| Not specified | 4 | 4 | 0 | 0 | ||||
| Risk stratification (ALL-BFM 2000 protocol) | .398 | .514 | .325 | .078 | ||||
| Standard risk | 57 (18.8) | 50 (19.5) | 2 (10.5) | 5 (18.8) | ||||
| Medium risk | 202 (66.7) | 173 (67.3) | 14 (73.7) | 15 (55.8) | ||||
| High risk | 44 (14.5) | 34 (13.2) | 3 (15.8) | 7 (25.9) | ||||
| Cumulative dose of purine analogs received up to week 50 (ALL-BFM 2000)|| (g/m2), median (min-max) | 10.2 (2.8-11.97) | 10.2 (2.8-11.97) | 10.2 (2.8-11.97) | 8.3 (2.8-10.22) | .215 | .133 | .517 | .112 |
| Time point of relapse (ALL-REZ BFM classification¶) | <.001 | .791 | <.001 | <.001 | ||||
| Very early | 75 (16.5) | 47 (12.4) | 11 (39.3) | 17 (36.2) | ||||
| Early | 112 (24.6) | 69 (18.2) | 15 (53.6) | 28 (59.6) | ||||
| Late | 268 (58.9) | 264 (69.5) | 2 (7.1) | 2 (4.3) | ||||
| Time of relapse with respect to primary treatment | <.001 | .146 | <.001 | <.001 | ||||
| On treatment | 130 (28.7) | 70 (18.5) | 25 (89.3) | 35 (74.5) | ||||
| Off treatment | 323 (71.3) | 308 (81.5) | 3 (10.7) | 12 (25.5) | ||||
| No data | 2 | 2 | 0 | 0 | ||||
| Time between initial diagnosis and first relapse (y), median (min-max) | 2.79 (0.34-12.97) | 3.11 (0.34-12.97) | 1.56 (0.90-2.86) | 1.70 (0.82-3.49) | <.001 | .181 | <.001 | <.001 |
| Site of relapse# | .949 | 1.000 | 1.000 | .856 | ||||
| BM isolated | 348 (76.5) | 292 (76.8) | 21 (75) | 35 (74.5) | ||||
| BM combined | 107 (23.5) | 88 (23.2) | 7 (25) | 12 (25.5) | ||||
| Risk stratification (ALL-REZ BFM 2002)** | <.001 | 1.000 | <.001 | <.001 | ||||
| Intermediate risk (S2) | 307 (67.5) | 289 (76.1) | 7 (25) | 11 (23.4) | ||||
| High risk (S3/4) | 148 (32.5) | 91 (23.9) | 21 (75) | 36 (76.6) | ||||
| Immunophenotype | .342 | .255 | .666 | .193 | ||||
| Pro-B-ALL | 26 (6.2) | 22 (6.2) | 3 (11.1) | 1 (2.5) | ||||
| Common ALL | 314 (74.8) | 265 (75.1) | 19 (70.4) | 30 (75) | ||||
| Pre-B-ALL | 70 (16.7) | 59 (16.7) | 5 (18.5) | 6 (15) | ||||
| Bilineage | 10 (2.4) | 7 (2) | 0 (0) | 3 (7.5) | ||||
| B lineage not specified | 35 | 27 | 1 | 7 |
| Parameter/variable . | Total, n (%) . | NT5C2 wild-type, n (%) . | NT5C2 clonal mut, n (%) . | NT5C2 subclonal mut, n (%) . | P* . | P† . | P‡ . | P§ . |
|---|---|---|---|---|---|---|---|---|
| Total | 455 | 380 | 28 | 47 | ||||
| Sex | .348 | .156 | .323 | .531 | ||||
| Male | 263 (57.8) | 220 (57.9) | 13 (46.4) | 30 (63.8) | ||||
| Female | 192 (42.2) | 160 (42.1) | 15 (53.6) | 17 (36.2) | ||||
| Age at initial diagnosis (y), median (min-max) | 4.81 (0.06-22.05) | 4.83 (0.28-21.65) | 4.17 (1.15-20.18) | 5.49 (0.06-22.05) | .949 | .844 | .923 | .757 |
| Initial treatment protocol | .680 | 1.000 | .445 | .717 | ||||
| German ALL-BFM | 327 (72.5) | 275 (73.1) | 19 (67.9) | 33 (70.2) | ||||
| German COALL | 116 (25.7) | 95 (25.3) | 8 (28.6) | 13 (27.7) | ||||
| Other | 8 (1.8) | 6 (1.6) | 1 (3.6) | 1 (2.1) | ||||
| Not specified | 4 | 4 | 0 | 0 | ||||
| Risk stratification (ALL-BFM 2000 protocol) | .398 | .514 | .325 | .078 | ||||
| Standard risk | 57 (18.8) | 50 (19.5) | 2 (10.5) | 5 (18.8) | ||||
| Medium risk | 202 (66.7) | 173 (67.3) | 14 (73.7) | 15 (55.8) | ||||
| High risk | 44 (14.5) | 34 (13.2) | 3 (15.8) | 7 (25.9) | ||||
| Cumulative dose of purine analogs received up to week 50 (ALL-BFM 2000)|| (g/m2), median (min-max) | 10.2 (2.8-11.97) | 10.2 (2.8-11.97) | 10.2 (2.8-11.97) | 8.3 (2.8-10.22) | .215 | .133 | .517 | .112 |
| Time point of relapse (ALL-REZ BFM classification¶) | <.001 | .791 | <.001 | <.001 | ||||
| Very early | 75 (16.5) | 47 (12.4) | 11 (39.3) | 17 (36.2) | ||||
| Early | 112 (24.6) | 69 (18.2) | 15 (53.6) | 28 (59.6) | ||||
| Late | 268 (58.9) | 264 (69.5) | 2 (7.1) | 2 (4.3) | ||||
| Time of relapse with respect to primary treatment | <.001 | .146 | <.001 | <.001 | ||||
| On treatment | 130 (28.7) | 70 (18.5) | 25 (89.3) | 35 (74.5) | ||||
| Off treatment | 323 (71.3) | 308 (81.5) | 3 (10.7) | 12 (25.5) | ||||
| No data | 2 | 2 | 0 | 0 | ||||
| Time between initial diagnosis and first relapse (y), median (min-max) | 2.79 (0.34-12.97) | 3.11 (0.34-12.97) | 1.56 (0.90-2.86) | 1.70 (0.82-3.49) | <.001 | .181 | <.001 | <.001 |
| Site of relapse# | .949 | 1.000 | 1.000 | .856 | ||||
| BM isolated | 348 (76.5) | 292 (76.8) | 21 (75) | 35 (74.5) | ||||
| BM combined | 107 (23.5) | 88 (23.2) | 7 (25) | 12 (25.5) | ||||
| Risk stratification (ALL-REZ BFM 2002)** | <.001 | 1.000 | <.001 | <.001 | ||||
| Intermediate risk (S2) | 307 (67.5) | 289 (76.1) | 7 (25) | 11 (23.4) | ||||
| High risk (S3/4) | 148 (32.5) | 91 (23.9) | 21 (75) | 36 (76.6) | ||||
| Immunophenotype | .342 | .255 | .666 | .193 | ||||
| Pro-B-ALL | 26 (6.2) | 22 (6.2) | 3 (11.1) | 1 (2.5) | ||||
| Common ALL | 314 (74.8) | 265 (75.1) | 19 (70.4) | 30 (75) | ||||
| Pre-B-ALL | 70 (16.7) | 59 (16.7) | 5 (18.5) | 6 (15) | ||||
| Bilineage | 10 (2.4) | 7 (2) | 0 (0) | 3 (7.5) | ||||
| B lineage not specified | 35 | 27 | 1 | 7 |
Values of P < .05 are depicted in bold.
BM, bone marrow; CR2, second complete remission; MRD, minimal residual disease; mut, mutation.
P value calculated among all 3 groups.
P value calculated between clonal and subclonal NT5C2 mutations.
P value calculated between clonal NT5C2 mutations and wild-type.
P value calculated between subclonal NT5C2 mutations and wild-type.
Corresponds to the end of intensive treatment phase.
Time of relapse: very early, <18 mo after initial diagnosis of ALL; early, ≥18 mo after initial diagnosis of ALL; late, ≥6 mo after completion of primary treatment.
Site of relapse: isolated bone marrow, no evidence of extramedullary disease; combined bone marrow, >5% leukemic cells in the bone marrow combined with central nervous system, testis, or other extramedullary disease.
Relapse risk group: high risk, early isolated or very early isolated or combined bone marrow relapse of BCP-ALL; intermediate risk, late isolated or combined bone marrow relapse or early combined bone marrow relapse of BCP-ALL.