Clinical characteristics of cohorts 1 and 2
| Parameter . | Variable . | Total . | Cohort 1 . | P value . | Total . | Cohort 2 . | ||
|---|---|---|---|---|---|---|---|---|
| Relapse . | CCR . | Relapse . | CCR . | |||||
| N (%) . | n (%) . | n (%) . | N (%) . | n (%) . | n (%) . | |||
| Total | 160 | 81 | 79 | 226 | 30 (13.3) | 196 (86.7) | ||
| BFM study protocol | 1995 | 19 (11.9) | 11 (13.6) | 8 (10.1) | .80 | 0 | 0 | 0 |
| 2000 | 99 (61.9) | 49 (60.5) | 50 (63.3) | 80 (35.4) | 7 (23.3) | 73 (37.2) | ||
| 2009 | 42 (26.3) | 21 (25.9) | 21 (26.6) | 95 (42) | 15 (50) | 80 (40.8) | ||
| 2017 | 0 | 0 | 0 | 51 (22.6) | 8 (26.7) | 43 (21.9) | ||
| Sex | Male | 119 (74.4) | 59 (72.8) | 60 (75.9) | .65 | 166 (73.8) | 22 (73.3) | 144 (73.8) |
| Female | 41 (25.6) | 22 (27.2) | 19 (24.1) | 59 (26.2) | 8 (26.7) | 51 (26.2) | ||
| No data | 0 | 0 | 0 | 1 | 0 | 1 | ||
| Risk stratification | SR | 4 (2.5) | 2 (2.5) | 2 (2.5) | .9 | 30 (13.3) | 1 (3.3) | 29 (14.9) |
| MR | 60 (37.5) | 29 (35.8) | 31 (39.2) | 103 (45.8) | 10 (33.3) | 93 (47.7) | ||
| HR | 96 (60) | 50 (61.7) | 46 (58.2) | 92 (40.9) | 19 (63.3) | 73 (37.4) | ||
| No data | 0 | 0 | 0 | 1 | 0 | 1 | ||
| Age at initial diagnosis | Median age (min-max), y | 9.9 (1.0-17.9) | 9.2 (1.0-17.9) | 9.4 (1.2-17.8) | .62 | |||
| No data | 226 | 30 | 196 | |||||
| Prednisone response | Good | 75 (47.8) | 35 (44.9) | 39 (46.8) | .57 | 143 (65.6) | 15 (50) | 128 (68.1) |
| Poor | 83 (52.9) | 43 (55.1) | 40 (50.6) | 75 (34.4) | 15 (50) | 60 (31.9) | ||
| No data | 3 | 3 | 0 | 8 | 0 | 8 | ||
| MRD1 (day 33)∗ | Low (<10−3) | 48 (36.6) | 19 (29.7) | 29 (43.3) | .11 | 107 (51.7) | 9 (34.6) | 88 (51.8) |
| High (≥10−3) | 83 (63.4) | 45 (70.3) | 38 (56.7) | 100 (48.3) | 17 (65.4) | 82 (48.2) | ||
| No data | 29 | 17 | 12 | 19 | 4 | 26 | ||
| MRD2 (day 78)∗ | Low (<10−3) | 95 (72) | 44 (67.7) | 51 (76.1) | .28 | 138 (69.3) | 15 (57.7) | 112 (69.1) |
| High (≥10−3) | 37 (28) | 21 (32.3) | 16 (23.9) | 61 (30.7) | 11 (42.3) | 50 (30.9) | ||
| No data | 28 | 16 | 12 | 27 | 4 | 34 | ||
| Stem cell transplantation in first remission | Yes | 33 (20.6) | 15 (18.5) | 18 (22.8) | .51 | 39 (17.3) | 15 (50) | 24 (12.2) |
| No | 127 (79.4) | 66 (81.5) | 61 (77.2) | 187 (82.7) | 15 (50) | 172 (87.8) | ||
| Time to relapse | Median time (min-max), y | 1.6 (0.17-7.08) | — | — | — | |||
| No data | 21 | 30 | ||||||
| Parameter . | Variable . | Total . | Cohort 1 . | P value . | Total . | Cohort 2 . | ||
|---|---|---|---|---|---|---|---|---|
| Relapse . | CCR . | Relapse . | CCR . | |||||
| N (%) . | n (%) . | n (%) . | N (%) . | n (%) . | n (%) . | |||
| Total | 160 | 81 | 79 | 226 | 30 (13.3) | 196 (86.7) | ||
| BFM study protocol | 1995 | 19 (11.9) | 11 (13.6) | 8 (10.1) | .80 | 0 | 0 | 0 |
| 2000 | 99 (61.9) | 49 (60.5) | 50 (63.3) | 80 (35.4) | 7 (23.3) | 73 (37.2) | ||
| 2009 | 42 (26.3) | 21 (25.9) | 21 (26.6) | 95 (42) | 15 (50) | 80 (40.8) | ||
| 2017 | 0 | 0 | 0 | 51 (22.6) | 8 (26.7) | 43 (21.9) | ||
| Sex | Male | 119 (74.4) | 59 (72.8) | 60 (75.9) | .65 | 166 (73.8) | 22 (73.3) | 144 (73.8) |
| Female | 41 (25.6) | 22 (27.2) | 19 (24.1) | 59 (26.2) | 8 (26.7) | 51 (26.2) | ||
| No data | 0 | 0 | 0 | 1 | 0 | 1 | ||
| Risk stratification | SR | 4 (2.5) | 2 (2.5) | 2 (2.5) | .9 | 30 (13.3) | 1 (3.3) | 29 (14.9) |
| MR | 60 (37.5) | 29 (35.8) | 31 (39.2) | 103 (45.8) | 10 (33.3) | 93 (47.7) | ||
| HR | 96 (60) | 50 (61.7) | 46 (58.2) | 92 (40.9) | 19 (63.3) | 73 (37.4) | ||
| No data | 0 | 0 | 0 | 1 | 0 | 1 | ||
| Age at initial diagnosis | Median age (min-max), y | 9.9 (1.0-17.9) | 9.2 (1.0-17.9) | 9.4 (1.2-17.8) | .62 | |||
| No data | 226 | 30 | 196 | |||||
| Prednisone response | Good | 75 (47.8) | 35 (44.9) | 39 (46.8) | .57 | 143 (65.6) | 15 (50) | 128 (68.1) |
| Poor | 83 (52.9) | 43 (55.1) | 40 (50.6) | 75 (34.4) | 15 (50) | 60 (31.9) | ||
| No data | 3 | 3 | 0 | 8 | 0 | 8 | ||
| MRD1 (day 33)∗ | Low (<10−3) | 48 (36.6) | 19 (29.7) | 29 (43.3) | .11 | 107 (51.7) | 9 (34.6) | 88 (51.8) |
| High (≥10−3) | 83 (63.4) | 45 (70.3) | 38 (56.7) | 100 (48.3) | 17 (65.4) | 82 (48.2) | ||
| No data | 29 | 17 | 12 | 19 | 4 | 26 | ||
| MRD2 (day 78)∗ | Low (<10−3) | 95 (72) | 44 (67.7) | 51 (76.1) | .28 | 138 (69.3) | 15 (57.7) | 112 (69.1) |
| High (≥10−3) | 37 (28) | 21 (32.3) | 16 (23.9) | 61 (30.7) | 11 (42.3) | 50 (30.9) | ||
| No data | 28 | 16 | 12 | 27 | 4 | 34 | ||
| Stem cell transplantation in first remission | Yes | 33 (20.6) | 15 (18.5) | 18 (22.8) | .51 | 39 (17.3) | 15 (50) | 24 (12.2) |
| No | 127 (79.4) | 66 (81.5) | 61 (77.2) | 187 (82.7) | 15 (50) | 172 (87.8) | ||
| Time to relapse | Median time (min-max), y | 1.6 (0.17-7.08) | — | — | — | |||
| No data | 21 | 30 | ||||||
Patients of cohort 1 (n = 160) are classified into 2 different groups according to their outcome: patients with relapse (n = 81) and patients who have remained in continuous complete remissions for >3 years (n = 79). The 2 groups were matched according to the parameters shown, which were equally distributed between both groups. P values were either assessed by χ2 test for categorical variables or by Mann-Whitney U test for the continuous variable “age.” Statistical significance was defined as P < .05. P values were not adjusted for multiple testing because of the hypothesis-generating concept of our study. Patients of cohort 2 were a randomly selected group of 226 patients with T-ALL at initial diagnosis who were treated on ALL-BFM protocols. Of these, 30 patients later relapsed whereas 196 patients had remained in continuous complete remission for >3 years. The clinical characteristics “age at initial diagnosis” and “time to relapse” were not available for these patients.
CCR, continuous complete remissions; max, maximum; min, minimum; MR, medium risk; MRD1/2, minimal residual disease; SR, standard risk.
MRD measured at day 33 and day 78 of induction therapy: low level, <10−3 leukemic cells; high level, ≥10−3 leukemic cells in bone marrow aspirates.