Subject characteristics and outcomes (N = 814)
| Variable . | MRD− . | MRD+ . | P† . | MRD+ . | P‡ . | DLI . | P§ . | ||
|---|---|---|---|---|---|---|---|---|---|
| IL-2 . | DLI . | Chemo-therapy . | No chemo-therapy . | ||||||
| No. of subjects | 709 | 105 | 49 | 56 | 32 | 24 | |||
| Subject age, y (range) | 29 (2-59) | 23 (4-59) | .012 | 25 (4-59) | 22 (6-55) | .882 | 20 (6-54) | 24.5 (12-55) | .379 |
| Subject sex, n (%) | .556 | .181 | .938 | ||||||
| Male | 438 (61.8) | 68 (64.8) | 35 (71.4) | 33 (58.9) | 19 (59.4) | 14 (58.3) | |||
| Female | 271 (38.2) | 37 (35.2) | 14 (28.6) | 23 (41.1) | 13 (40.6) | 10 (41.7) | |||
| Disease type, n (%) | .170 | .950 | .940 | ||||||
| AML | 378 (53.3) | 61 (58.1) | 29 (59.2) | 32 (57.1) | 18 (56.3) | 14 (58.3) | |||
| ALL | 247 (34.8) | 38 (36.2) | 17 (34.7) | 21 (37.5) | 12 (37.5) | 9 (37.5) | |||
| MDS-RAEB | 84 (11.8) | 6 (5.7) | 3 (6.1) | 3 (5.4) | 2 (6.3) | 1 (4.2) | |||
| Remission state, n (%) | .103 | .037 | .679 | ||||||
| CR1 | 559 (88.6) | 85 (81.0) | 42 (85.7) | 43 (76.8) | 22 (73.3) | 18 (78.3) | |||
| CR2 | 72 (11.4) | 20 (19.0) | 7 (14.3) | 13 (23.2) | 8 (26.7) | 5 (21.7) | |||
| Cytogenetic subGroup, n (%)* | .103 | .615 | .626 | ||||||
| Intermediate | 466 (65.7) | 62 (59.0) | 30 (61.2) | 32 (57.1) | 22 (68.8) | 16 (66.7) | |||
| Poor | 63 (8.9) | 14 (13.3) | 5 (10.2) | 9 (16.1) | 4 (12.5) | 5 (20.8) | |||
| Not available | 180 (25.4) | 29 (27.6) | 14 (28.6) | 15 (26.8) | 8 (18.8) | 3 (12.5) | |||
| No. of induction chemotherapies, n (%) | .095 | .989 | .892 | ||||||
| 1 | 433 (68.6) | 66 (62.9) | 31 (63.3) | 35 (62.5) | 20 (66.7) | 14 (60.9) | |||
| 2 | 149 (23.6) | 22 (20.9) | 10 (20.4) | 12 (21.4) | 6 (20.0) | 5 (21.7) | |||
| > 2 | 49 (7.8) | 17 (16.2) | 8 (16.3) | 9 (16.1) | 4 (13.3) | 4 (17.4) | |||
| Type of donor, n (%) | .080 | .002 | .214 | ||||||
| HLA-identical related | 215 (30.3) | 40 (38.1) | 14 (28.6) | 26 (46.4) | 13 (40.6) | 13 (54.2) | |||
| HLA-haploidentical related | 438 (61.8) | 53 (50.5) | 24 (49.0) | 29 (51.8) | 19 (59.4) | 10 (41.7) | |||
| Unrelated | 56 (7.9) | 12 (11.4) | 11 (22.4) | 1 (1.8) | 0 (0.0) | 1 (4.2) | |||
| Conditioning regimen, n (%) | .003 | .376 | .797 | ||||||
| TBI-based | 2 (0.3) | 4 (3.8) | 1 (2.0) | 1 (1.8) | 1 (3.1) | 2 (8.3) | |||
| BU-based | 707 (99.7) | 101 (96.2) | 48 (98.0) | 55 (98.2) | 31 (96.9) | 22 (91.7) | |||
| Acute GvHD pre-MRD, n (%) | 15 (30.6) | 18 (32.1) | .762 | 11 (34.3) | 7 (29.1) | .370 | |||
| ≥ Grade 2 | 8 (16.3) | 8 (14.3) | .708 | 6 (18.8) | 2 (8.3) | .269 | |||
| ≥ Grade 3 | 0 (0.0) | 0 (0.0) | .989 | 0 (0.0) | 0 (0.0) | 1.000 | |||
| Chronic GvHD pre-MRD, n (%) | 13 (26.5) | 12 (21.4) | .326 | 7 (21.9) | 5 (20.8) | .788 | |||
| Extensive GvHD pre-MRD | 4 (8.2) | 5 (8.9) | .768 | 3 (9.3) | 2 (8.3) | .990 | |||
| Chimerism status pre-MRD, n (%) | .856 | .986 | |||||||
| Full donor | 46 (93.9) | 54 (96.4) | 31 (96.9) | 23 (95.8) | |||||
| Mixed | 3 (6.1) | 2 (3.6) | 1 (3.1) | 1 (4.2) | |||||
| Full recipient | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |||||
| Interval from HSCT to MRD, d (range) | 140 (30-365) | 135 (30-435) | .455 | 132 (30-435) | 135 (30-365) | .980 | |||
| Chemotherapy before intervention, n (%) | 0 (0.0) | 32 (57.1) | .001 | ||||||
| Discontinuing immunosuppressions before intervention, n (%) | 26 (53.1) | 28 (50.0) | .754 | 16 (50.0) | 12 (50.0) | .989 | |||
| Acute GvHD after intervention, n (%) | 10.2 | 30.8 | .017 | 33.3 | 29.0 | .655 | |||
| ≥ Grade 2 | 8.2 | 27.9 | .017 | 30.3 | 26.2 | .701 | |||
| ≥ Grade 3 | 4.1 | 8.4 | .471 | 9.8 | 7.3 | .752 | |||
| Chronic GvHD after intervention, n (%) | 37.3 | 42.9 | .982 | 45.5 | 39.4 | .934 | |||
| Extensive chronic GvHD | 30.5 | 34.2 | .858 | 39.4 | 30.1 | .283 | |||
| Incidence of TRM at 3 y after HSCT, n (%) | 19.7 | 12.7 | .080 | 11.4 | 14.4 | .897 | 22.4 | 8.5 | .055 |
| Actual relapse rate, n (%) | 103 (14.5) | 37 (35.2) | .000 | 25 (51.0) | 12 (21.4) | .002 | 5 (15.6) | 7 (29.2) | .222 |
| Incidence of relapse at 3 y after HSCT, n (%) | 18.1 | 46.0 | .000 | 64.4 | 27.8 | .001 | 26.4 | 32.7 | .822 |
| OS at 3 y after HSCT, n (%) | 66.0 | 44.0 | .005 | 28.1 | 58.3 | .022 | 60.5 | 57.8 | .496 |
| Median OS after HSCT, mo (95% CI) | 44.39 (33.87-54.90) | 33.17 (25.23-41.11) | .005 | 18.97 (3.13-34.80) | 38.53 (33.78-50.86) | .022 | 40.32 (33.78-50.86) | 38.53 (33.32-54.25) | .496 |
| DFS at 3 y after HSCT, n | 61.6 | 40.3 | .041 | 24.1 | 55.6 | .002 | 51.2 | 57.8 | .327 |
| Median DFS after HSCT, mo (95% CI) | 42.40 (33.85-54.90) | 28.00 (19.12-36.88) | .041 | 13.33 (8.78-17.88) | 38.53 (32.00-59.92) | .002 | 40.52 (32.0-49.04) | 38.53 (32.40-54.05) | .327 |
| Variable . | MRD− . | MRD+ . | P† . | MRD+ . | P‡ . | DLI . | P§ . | ||
|---|---|---|---|---|---|---|---|---|---|
| IL-2 . | DLI . | Chemo-therapy . | No chemo-therapy . | ||||||
| No. of subjects | 709 | 105 | 49 | 56 | 32 | 24 | |||
| Subject age, y (range) | 29 (2-59) | 23 (4-59) | .012 | 25 (4-59) | 22 (6-55) | .882 | 20 (6-54) | 24.5 (12-55) | .379 |
| Subject sex, n (%) | .556 | .181 | .938 | ||||||
| Male | 438 (61.8) | 68 (64.8) | 35 (71.4) | 33 (58.9) | 19 (59.4) | 14 (58.3) | |||
| Female | 271 (38.2) | 37 (35.2) | 14 (28.6) | 23 (41.1) | 13 (40.6) | 10 (41.7) | |||
| Disease type, n (%) | .170 | .950 | .940 | ||||||
| AML | 378 (53.3) | 61 (58.1) | 29 (59.2) | 32 (57.1) | 18 (56.3) | 14 (58.3) | |||
| ALL | 247 (34.8) | 38 (36.2) | 17 (34.7) | 21 (37.5) | 12 (37.5) | 9 (37.5) | |||
| MDS-RAEB | 84 (11.8) | 6 (5.7) | 3 (6.1) | 3 (5.4) | 2 (6.3) | 1 (4.2) | |||
| Remission state, n (%) | .103 | .037 | .679 | ||||||
| CR1 | 559 (88.6) | 85 (81.0) | 42 (85.7) | 43 (76.8) | 22 (73.3) | 18 (78.3) | |||
| CR2 | 72 (11.4) | 20 (19.0) | 7 (14.3) | 13 (23.2) | 8 (26.7) | 5 (21.7) | |||
| Cytogenetic subGroup, n (%)* | .103 | .615 | .626 | ||||||
| Intermediate | 466 (65.7) | 62 (59.0) | 30 (61.2) | 32 (57.1) | 22 (68.8) | 16 (66.7) | |||
| Poor | 63 (8.9) | 14 (13.3) | 5 (10.2) | 9 (16.1) | 4 (12.5) | 5 (20.8) | |||
| Not available | 180 (25.4) | 29 (27.6) | 14 (28.6) | 15 (26.8) | 8 (18.8) | 3 (12.5) | |||
| No. of induction chemotherapies, n (%) | .095 | .989 | .892 | ||||||
| 1 | 433 (68.6) | 66 (62.9) | 31 (63.3) | 35 (62.5) | 20 (66.7) | 14 (60.9) | |||
| 2 | 149 (23.6) | 22 (20.9) | 10 (20.4) | 12 (21.4) | 6 (20.0) | 5 (21.7) | |||
| > 2 | 49 (7.8) | 17 (16.2) | 8 (16.3) | 9 (16.1) | 4 (13.3) | 4 (17.4) | |||
| Type of donor, n (%) | .080 | .002 | .214 | ||||||
| HLA-identical related | 215 (30.3) | 40 (38.1) | 14 (28.6) | 26 (46.4) | 13 (40.6) | 13 (54.2) | |||
| HLA-haploidentical related | 438 (61.8) | 53 (50.5) | 24 (49.0) | 29 (51.8) | 19 (59.4) | 10 (41.7) | |||
| Unrelated | 56 (7.9) | 12 (11.4) | 11 (22.4) | 1 (1.8) | 0 (0.0) | 1 (4.2) | |||
| Conditioning regimen, n (%) | .003 | .376 | .797 | ||||||
| TBI-based | 2 (0.3) | 4 (3.8) | 1 (2.0) | 1 (1.8) | 1 (3.1) | 2 (8.3) | |||
| BU-based | 707 (99.7) | 101 (96.2) | 48 (98.0) | 55 (98.2) | 31 (96.9) | 22 (91.7) | |||
| Acute GvHD pre-MRD, n (%) | 15 (30.6) | 18 (32.1) | .762 | 11 (34.3) | 7 (29.1) | .370 | |||
| ≥ Grade 2 | 8 (16.3) | 8 (14.3) | .708 | 6 (18.8) | 2 (8.3) | .269 | |||
| ≥ Grade 3 | 0 (0.0) | 0 (0.0) | .989 | 0 (0.0) | 0 (0.0) | 1.000 | |||
| Chronic GvHD pre-MRD, n (%) | 13 (26.5) | 12 (21.4) | .326 | 7 (21.9) | 5 (20.8) | .788 | |||
| Extensive GvHD pre-MRD | 4 (8.2) | 5 (8.9) | .768 | 3 (9.3) | 2 (8.3) | .990 | |||
| Chimerism status pre-MRD, n (%) | .856 | .986 | |||||||
| Full donor | 46 (93.9) | 54 (96.4) | 31 (96.9) | 23 (95.8) | |||||
| Mixed | 3 (6.1) | 2 (3.6) | 1 (3.1) | 1 (4.2) | |||||
| Full recipient | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |||||
| Interval from HSCT to MRD, d (range) | 140 (30-365) | 135 (30-435) | .455 | 132 (30-435) | 135 (30-365) | .980 | |||
| Chemotherapy before intervention, n (%) | 0 (0.0) | 32 (57.1) | .001 | ||||||
| Discontinuing immunosuppressions before intervention, n (%) | 26 (53.1) | 28 (50.0) | .754 | 16 (50.0) | 12 (50.0) | .989 | |||
| Acute GvHD after intervention, n (%) | 10.2 | 30.8 | .017 | 33.3 | 29.0 | .655 | |||
| ≥ Grade 2 | 8.2 | 27.9 | .017 | 30.3 | 26.2 | .701 | |||
| ≥ Grade 3 | 4.1 | 8.4 | .471 | 9.8 | 7.3 | .752 | |||
| Chronic GvHD after intervention, n (%) | 37.3 | 42.9 | .982 | 45.5 | 39.4 | .934 | |||
| Extensive chronic GvHD | 30.5 | 34.2 | .858 | 39.4 | 30.1 | .283 | |||
| Incidence of TRM at 3 y after HSCT, n (%) | 19.7 | 12.7 | .080 | 11.4 | 14.4 | .897 | 22.4 | 8.5 | .055 |
| Actual relapse rate, n (%) | 103 (14.5) | 37 (35.2) | .000 | 25 (51.0) | 12 (21.4) | .002 | 5 (15.6) | 7 (29.2) | .222 |
| Incidence of relapse at 3 y after HSCT, n (%) | 18.1 | 46.0 | .000 | 64.4 | 27.8 | .001 | 26.4 | 32.7 | .822 |
| OS at 3 y after HSCT, n (%) | 66.0 | 44.0 | .005 | 28.1 | 58.3 | .022 | 60.5 | 57.8 | .496 |
| Median OS after HSCT, mo (95% CI) | 44.39 (33.87-54.90) | 33.17 (25.23-41.11) | .005 | 18.97 (3.13-34.80) | 38.53 (33.78-50.86) | .022 | 40.32 (33.78-50.86) | 38.53 (33.32-54.25) | .496 |
| DFS at 3 y after HSCT, n | 61.6 | 40.3 | .041 | 24.1 | 55.6 | .002 | 51.2 | 57.8 | .327 |
| Median DFS after HSCT, mo (95% CI) | 42.40 (33.85-54.90) | 28.00 (19.12-36.88) | .041 | 13.33 (8.78-17.88) | 38.53 (32.00-59.92) | .002 | 40.52 (32.0-49.04) | 38.53 (32.40-54.05) | .327 |
AML indicates acute myelogenous leukemia; MDS-RAEB, myelodysplastic syndrome–refractory anemia with excess blasts; CR, complete remission; BU, busulfan; and TBI, total body irradiation.
Cytogenetic subGroups were according to the published data.23-25
Comparison was performed between Group A and Groups B and C.
Comparison was performed between Groups B and C.
Comparison was performed between the subjects receiving chemotherapy prior to DLI and subjects not receiving chemotherapy in Group C.