Outcomes
| . | Total, n . | Events . | Cumulative incidence (95% CI)∗ . | Multivariate analysis† . | ||
|---|---|---|---|---|---|---|
| HR . | 95% CI . | P value . | ||||
| OS | ||||||
| HLA-matched/younger donor | 10 531 | 4 908 | 49.9 (48.8-50.9) | Ref | ||
| HLA-matched/older donor | 3 572 | 1 899 | 44.0 (42.2-45.7) | 1.18 | 1.12-1.25 | <.001 |
| PBM matched/younger donor | 357 | 186 | 45.4 (39.9-50.7) | 1.18 | 1.02-1.37 | .026 |
| PBM matched/older donor | 257 | 160 | 35.6 (29.6-41.7) | 1.48 | 1.26-1.73 | <.001 |
| PBM mismatched/younger donor | 616 | 356 | 39.4 (35.4-43.5) | 1.42 | 1.27-1.58 | <.001 |
| PBM mismatched/older donor | 339 | 234 | 29.0 (24.1-34.1) | 1.91 | 1.67-2.18 | <.001 |
| NRM | ||||||
| HLA-matched/younger donor | 10 531 | 2 138 | 21.6 (20.8-22.4) | Ref | ||
| HLA-matched/older donor | 3 572 | 893 | 26.1 (24.6-27.6) | 1.27 | 1.16-1.39 | <.001 |
| PBM matched/younger donor | 357 | 91 | 26.3 (21.8-31.1) | 1.27 | 0.98-1.65 | .072 |
| PBM matched/older donor | 257 | 96 | 38.3 (32.2-44.3) | 1.77 | 1.39-2.26 | <.001 |
| PBM mismatched/younger donor | 616 | 176 | 29.7 (26.0-33.5) | 1.63 | 1.36-1.96 | <.001 |
| PBM mismatched/older donor | 339 | 138 | 41.3 (36.0-46.5) | 2.10 | 1.69-2.62 | <.001 |
| Relapse (early/intermediate disease) | ||||||
| HLA-matched/younger donor | 6 898 | 1 866 | 28.3 (27.2-29.4) | Ref | ||
| HLA-matched/older donor | 2 329 | 673 | 30.0 (28.1-32.0) | 1.08 | 0.98-1.2 | .13 |
| PBM matched/younger donor | 229 | 68 | 30.3 (24.4-36.4) | 1.09 | 0.82-1.46 | .55 |
| PBM matched/older donor | 168 | 43 | 26.3 (19.7-33.2) | 1.17 | 0.83-1.64 | .37 |
| PBM mismatched/younger donor | 405 | 117 | 29.9 (25.4-34.5) | 0.96 | 0.76-1.22 | .76 |
| PBM mismatched/older donor | 236 | 69 | 30.1 (24.3-36.1) | 1.20 | 0.92-1.56 | .19 |
| Relapse (advanced disease) | ||||||
| HLA-matched/younger donor | 3 523 | 1 433 | 41.9 (40.2-43.5) | Ref | ||
| HLA-matched/older donor | 1 205 | 496 | 42.0 (39.1-44.8) | 1.01 | 0.9-1.14 | .87 |
| PBM matched/younger donor | 126 | 45 | 37.0 (28.4-45.6) | 0.90 | 0.64-1.26 | .55 |
| PBM matched/older donor | 89 | 29 | 33.8 (23.9-44) | 0.78 | 0.52-1.18 | .24 |
| PBM mismatched/younger donor | 206 | 88 | 43.7 (36.7-50.5) | 0.88 | 0.69-1.13 | .32 |
| PBM mismatched/older donor | 101 | 32 | 31.7 (22.9-40.9) | 0.75 | 0.48-1.17 | .21 |
| Chronic GVHD (peripheral blood) | ||||||
| HLA-matched/younger donor | 8 249 | 4 413 | 55.0 (35.2-39.5) | Ref | ||
| HLA-matched/older donor | 2 845 | 1 454 | 52.2 (39.0-46.7) | 0.96 | 0.89-1.03 | .21 |
| PBM matched/younger donor | 277 | 145 | 53.7 (26.2-48.2) | 1.05 | 0.86-1.28 | .65 |
| PBM matched/older donor | 197 | 92 | 47.6 (35.1-61.6) | 0.92 | 0.72-1.18 | .52 |
| PBM mismatched/younger donor | 457 | 226 | 50.3 (35.1-51.4) | 1.11 | 0.95-1.29 | .21 |
| PBM mismatched/older donor | 261 | 112 | 43.5 (37.8-61.0) | 0.91 | 0.73-1.12 | .36 |
| Chronic GVHD (bone marrow) | ||||||
| HLA-matched/younger donor | 2 013 | 730 | 37.3 (53.9-56.1) | Ref | ||
| HLA-matched/older donor | 652 | 275 | 42.8 (50.3-54.1) | 1.23 | 1.05-1.43 | .009 |
| PBM matched/younger donor | 74 | 27 | 37.2 (47.5-59.5) | 1.01 | 0.64-1.58 | .972 |
| PBM matched/older donor | 53 | 26 | 49.1 (40.4-54.4) | 1.83 | 1.19-2.8 | .005 |
| PBM mismatched/younger donor | 143 | 61 | 43.4 (45.5-54.8) | 1.17 | 0.86-1.59 | .318 |
| PBM mismatched/older donor | 70 | 35 | 50.0 (37.4-49.5) | 1.44 | 0.96-2.15 | .08 |
| Grade 3/4 acute GVHD, day 100 (peripheral blood) | ||||||
| HLA-matched/younger donor | 8 108 | 1 253 | 15.5 (14.68-16.25) | Ref | ||
| HLA-matched/older donor | 2 749 | 496 | 18.0 (16.63-19.5) | 1.10 | 0.98-1.24 | .123 |
| PBM matched/younger donor | 268 | 58 | 21.6 (16.93-26.74) | 1.52 | 1.12-2.05 | .007 |
| PBM matched/older donor | 190 | 38 | 20.0 (14.65-25.96) | 1.22 | 0.83-1.79 | .306 |
| PBM mismatched/younger donor | 455 | 103 | 22.6 (18.91-26.58) | 1.41 | 1.11-1.8 | .005 |
| PBM mismatched/older donor | 256 | 73 | 28.5 (23.12-34.13) | 1.59 | 1.19-2.13 | .002 |
| Grade 3/4 acute GVHD, day 100 (bone marrow) | ||||||
| HLA-matched/younger donor | 1 981 | 278 | 14.0 (12.55-15.6) | Ref | ||
| HLA-matched/older donor | 641 | 83 | 13.0 (10.49-15.68) | 1.00 | 0.77-1.31 | .998 |
| PBM matched/younger donor | 75 | 14 | 18.7(10.82-28.18) | 1.12 | 0.55-2.26 | .761 |
| PBM matched/older donor | 54 | 20 | 37.0 (24.42-49.67) | 3.00 | 1.74-5.16 | <.001 |
| PBM mismatched/younger donor | 144 | 42 | 29.2 (21.98-36.71) | 2.00 | 1.36-2.95 | <.001 |
| PBM mismatched/older donor | 71 | 23 | 32.4 (21.9-43.32) | 2.67 | 1.65-4.32 | <.001 |
| . | Total, n . | Events . | Cumulative incidence (95% CI)∗ . | Multivariate analysis† . | ||
|---|---|---|---|---|---|---|
| HR . | 95% CI . | P value . | ||||
| OS | ||||||
| HLA-matched/younger donor | 10 531 | 4 908 | 49.9 (48.8-50.9) | Ref | ||
| HLA-matched/older donor | 3 572 | 1 899 | 44.0 (42.2-45.7) | 1.18 | 1.12-1.25 | <.001 |
| PBM matched/younger donor | 357 | 186 | 45.4 (39.9-50.7) | 1.18 | 1.02-1.37 | .026 |
| PBM matched/older donor | 257 | 160 | 35.6 (29.6-41.7) | 1.48 | 1.26-1.73 | <.001 |
| PBM mismatched/younger donor | 616 | 356 | 39.4 (35.4-43.5) | 1.42 | 1.27-1.58 | <.001 |
| PBM mismatched/older donor | 339 | 234 | 29.0 (24.1-34.1) | 1.91 | 1.67-2.18 | <.001 |
| NRM | ||||||
| HLA-matched/younger donor | 10 531 | 2 138 | 21.6 (20.8-22.4) | Ref | ||
| HLA-matched/older donor | 3 572 | 893 | 26.1 (24.6-27.6) | 1.27 | 1.16-1.39 | <.001 |
| PBM matched/younger donor | 357 | 91 | 26.3 (21.8-31.1) | 1.27 | 0.98-1.65 | .072 |
| PBM matched/older donor | 257 | 96 | 38.3 (32.2-44.3) | 1.77 | 1.39-2.26 | <.001 |
| PBM mismatched/younger donor | 616 | 176 | 29.7 (26.0-33.5) | 1.63 | 1.36-1.96 | <.001 |
| PBM mismatched/older donor | 339 | 138 | 41.3 (36.0-46.5) | 2.10 | 1.69-2.62 | <.001 |
| Relapse (early/intermediate disease) | ||||||
| HLA-matched/younger donor | 6 898 | 1 866 | 28.3 (27.2-29.4) | Ref | ||
| HLA-matched/older donor | 2 329 | 673 | 30.0 (28.1-32.0) | 1.08 | 0.98-1.2 | .13 |
| PBM matched/younger donor | 229 | 68 | 30.3 (24.4-36.4) | 1.09 | 0.82-1.46 | .55 |
| PBM matched/older donor | 168 | 43 | 26.3 (19.7-33.2) | 1.17 | 0.83-1.64 | .37 |
| PBM mismatched/younger donor | 405 | 117 | 29.9 (25.4-34.5) | 0.96 | 0.76-1.22 | .76 |
| PBM mismatched/older donor | 236 | 69 | 30.1 (24.3-36.1) | 1.20 | 0.92-1.56 | .19 |
| Relapse (advanced disease) | ||||||
| HLA-matched/younger donor | 3 523 | 1 433 | 41.9 (40.2-43.5) | Ref | ||
| HLA-matched/older donor | 1 205 | 496 | 42.0 (39.1-44.8) | 1.01 | 0.9-1.14 | .87 |
| PBM matched/younger donor | 126 | 45 | 37.0 (28.4-45.6) | 0.90 | 0.64-1.26 | .55 |
| PBM matched/older donor | 89 | 29 | 33.8 (23.9-44) | 0.78 | 0.52-1.18 | .24 |
| PBM mismatched/younger donor | 206 | 88 | 43.7 (36.7-50.5) | 0.88 | 0.69-1.13 | .32 |
| PBM mismatched/older donor | 101 | 32 | 31.7 (22.9-40.9) | 0.75 | 0.48-1.17 | .21 |
| Chronic GVHD (peripheral blood) | ||||||
| HLA-matched/younger donor | 8 249 | 4 413 | 55.0 (35.2-39.5) | Ref | ||
| HLA-matched/older donor | 2 845 | 1 454 | 52.2 (39.0-46.7) | 0.96 | 0.89-1.03 | .21 |
| PBM matched/younger donor | 277 | 145 | 53.7 (26.2-48.2) | 1.05 | 0.86-1.28 | .65 |
| PBM matched/older donor | 197 | 92 | 47.6 (35.1-61.6) | 0.92 | 0.72-1.18 | .52 |
| PBM mismatched/younger donor | 457 | 226 | 50.3 (35.1-51.4) | 1.11 | 0.95-1.29 | .21 |
| PBM mismatched/older donor | 261 | 112 | 43.5 (37.8-61.0) | 0.91 | 0.73-1.12 | .36 |
| Chronic GVHD (bone marrow) | ||||||
| HLA-matched/younger donor | 2 013 | 730 | 37.3 (53.9-56.1) | Ref | ||
| HLA-matched/older donor | 652 | 275 | 42.8 (50.3-54.1) | 1.23 | 1.05-1.43 | .009 |
| PBM matched/younger donor | 74 | 27 | 37.2 (47.5-59.5) | 1.01 | 0.64-1.58 | .972 |
| PBM matched/older donor | 53 | 26 | 49.1 (40.4-54.4) | 1.83 | 1.19-2.8 | .005 |
| PBM mismatched/younger donor | 143 | 61 | 43.4 (45.5-54.8) | 1.17 | 0.86-1.59 | .318 |
| PBM mismatched/older donor | 70 | 35 | 50.0 (37.4-49.5) | 1.44 | 0.96-2.15 | .08 |
| Grade 3/4 acute GVHD, day 100 (peripheral blood) | ||||||
| HLA-matched/younger donor | 8 108 | 1 253 | 15.5 (14.68-16.25) | Ref | ||
| HLA-matched/older donor | 2 749 | 496 | 18.0 (16.63-19.5) | 1.10 | 0.98-1.24 | .123 |
| PBM matched/younger donor | 268 | 58 | 21.6 (16.93-26.74) | 1.52 | 1.12-2.05 | .007 |
| PBM matched/older donor | 190 | 38 | 20.0 (14.65-25.96) | 1.22 | 0.83-1.79 | .306 |
| PBM mismatched/younger donor | 455 | 103 | 22.6 (18.91-26.58) | 1.41 | 1.11-1.8 | .005 |
| PBM mismatched/older donor | 256 | 73 | 28.5 (23.12-34.13) | 1.59 | 1.19-2.13 | .002 |
| Grade 3/4 acute GVHD, day 100 (bone marrow) | ||||||
| HLA-matched/younger donor | 1 981 | 278 | 14.0 (12.55-15.6) | Ref | ||
| HLA-matched/older donor | 641 | 83 | 13.0 (10.49-15.68) | 1.00 | 0.77-1.31 | .998 |
| PBM matched/younger donor | 75 | 14 | 18.7(10.82-28.18) | 1.12 | 0.55-2.26 | .761 |
| PBM matched/older donor | 54 | 20 | 37.0 (24.42-49.67) | 3.00 | 1.74-5.16 | <.001 |
| PBM mismatched/younger donor | 144 | 42 | 29.2 (21.98-36.71) | 2.00 | 1.36-2.95 | <.001 |
| PBM mismatched/older donor | 71 | 23 | 32.4 (21.9-43.32) | 2.67 | 1.65-4.32 | <.001 |
Other significant predictors were: OS: disease (MDS [HR, 0.76; 95% CI, 0.71-0.81; P < .001]); advanced stage disease (HR, 1.71; 95% CI, 1.62-1.80; P < .001) recipient age (40-55 years [HR, 1.20; 95% CI, 1.13-1.29; P < .001], 55.1-65 years [HR, 1.46; 95% CI, 1.37-1.56; P < .001], and >65 years [HR, 1.62; 95% CI, 1.50-1.73; P < .001]), KPS score of 90-100 (HR, 0.81; 95% CI, 0.77-0.84; P < .001), HCT-CI of ≥2 (HR, 1.27; 95% CI, 1.21-1.33; P < .001), female donor to male recipient (HR, 1.08; 95% CI, 1.01-1.15; P = .02), donor/recipient CMV−/CMV+ status (HR, 1.11; 95% CI, 1.06-1.16; P < .001), time to HCT from diagnosis (6-12 months [HR, 1.16; 95% CI, 1.10-1.22; P < .001]), year of HCT (2010-2012 [HR, 0.84; 95% CI, 0.78-0.91; P < .001], 2013-2015 [HR, 0.74; 95% CI, 0.68-0.79; P < .001], and 2016-2018 [HR, 0.64; 95% CI, 0.59-0.69; P < .001]). NRM: disease (ALL [HR, 1.35; 95% CI, 1.21-1.51; P < .001], and MDS [HR, 1.56; 95% CI, 1.42-1.71; P < .001)], recipient age (40-55 years [HR, 1.50; 95% CI, 1.33-1.70; P < .001], 55.1-65 years [HR, 1.61; 95% CI, 1.42-1.82; P < .001], and >65 years [HR, 1.67; 95% CI, 1.46-1.91; P < .001]), CsA-based GVHD prophylaxis (HR, 1.22; 95% CI, 1.09-1.36; P < .001), in vivo TCD (HR, 0.87; 95% CI, 0.80-0.94; P = .001), KPS score of 90 to 100 (HR, 0.82; 95% CI, 0.75-0.88; P < .001), HCT-CI score of ≥2 (HR, 1.37; 95% CI, 1.26-1.49; P < .001), time to HCT from diagnosis (6-12 months [HR, 1.14; 95% CI, 1.04-1.26; P = .008], 12-24 months [HR, 1.23; 95% CI, 1.09-1.38; P = .001], and >24 months [HR, 1.28; 95% CI, 1.14-1.44; P < .001]), year of HCT (2013-2015 [HR, 0.85; 95% CI, 0.77-0.93; P < .001], and 2016-2018 [HR, 0.71; 95% CI, 0.64-0.78; P < .001]), DPB1 nonpermissive GVH mismatch (HR, 1.14; 95% CI, 1.03-1.25; P = .008). Relapse (early/intermediate risk disease): disease (ALL [HR, 0.82; 95% CI, 0.74-0.91; P < .001], and MDS [HR, 0.78; 95% CI, 0.66-0.92; P = .004]), recipient age (55.1-65 years [HR, 1.20; 95% CI, 1.08-1.34; P = .001), and >65 years [HR, 1.28; 95% CI, 1.11-1.46; P < .001]), NMA/RIC (HR, 1.27; 95% CI, 1.14-1.41; P < .001), in vivo TCD (HR, 1.15; 95% CI, 1.05-1.25; P = .002), KPS score of 90 to 100 (HR, 0.89; 95% CI, 0.82-0.97; P = .011), time to HCT from diagnosis (>24 months [HR, 0.86; 95% CI, 0.74-1.00; P = .047]), year of HCT (2016-2018 [HR, 0.82; 95% CI, 0.74-0.90; P < .001]), DPB1 nonpermissive GVH mismatch (HR, 0.84; 95% CI, 0.75-0.94; P = .003). Relapse (advanced risk disease): disease (MDS [HR, 0.41; 95% CI, 0.37-0.45; P < .001]), recipient age of >65 years (HR, 1.23; 95% CI, 1.10-1.38; P < .001), in vivo TCD (HR, 1.18; 95% CI, 1.07-1.30; P = .001); PB graft (HR, 1.18; 95% CI, 1.02-1.35; P = .02), HCT-CI of ≥2 (HR, 1.17; 95% CI, 1.05-1.30; P = .004), time to HCT from diagnosis (12-24 months [HR, 0.79; 95% CI, 0.69-0.91; P = .001), and >24 months [HR, 0.60; 95% CI, 0.51-0.70; P < .001]), year of HCT (2010-2012 [HR, 0.73; 95% CI, 0.61-0.87; P < .001], 2013-2015 [HR, 0.81; 95% CI, 0.68-0.96; P = .013], 2016-2018 [HR, 0.76; 95% CI, 0.64-0.91; P = .002]), DPB1 nonpermissive GVH mismatch (HR, 0.85, 95%0.74-0.96; P = .011). Chronic GVHD (PB graft): disease (ALL [HR, 0.91, 95% CI, 10.84-0.99; P = .02), MDS [HR, 1.26; 95% CI, 1.16-1.36; P < .001]), advanced disease stage (HR, 0.80; 95% CI, 0.74-0.86; P < .001), recipient age (40-55 years [HR, 0.90; 95% CI, 0.83-0.98; P = .02], 55.1-65 years [HR, 0.86; 95% CI, 0.79-0.94; P < .001], and >65 years (HR, 0.78; 95% CI, 0.71-0.86; P < .001]), in vivo TCD (HR, 0.61; 95% CI, 0.57-0.65; P < .001), KPS score of 90 to 100 (HR, 1.20; 95% CI, 1.13-1.27; P < .001), HCT-CI of ≥2 (HR, 0.93; 95% CI, 0.88-0.99; P = .02), time from diagnosis to HCT of 6 to12 months (HR, 0.88; 95% CI, 0.82-0.95; P < .001). Chronic GVHD (BM graft): MDS (HR, 1.36; 95% CI, 1.14-1.63; P = .001), advanced disease stage (HR, 0.77; 95% CI, 0.66-0.91; P = .002), recipient age of >65 years (HR, 0.65; 95% CI, 0.51-0.84; P = .001), in vivo TCD (HR, 0.68; 95% CI, 0.59-0.78; P < .001), female donor to male recipient (HR, 1.40; 95% CI, 1.18-1.67; P < .001). Acute GVHD, grade 3/4 (PB graft): disease (ALL [HR, 1.42; 95 % CI 1.24-1.62; P < .001], and MDS [HR, 1.39; 95% CI, 1.21-1.59; P < .001]), advanced disease stage (HR, 1.23; 95% CI, 1.09-1.39; P = .002), NMA/RIC conditioning (HR, 0.79; 95% CI, 0.71-0.88; P < .001), in vivo TCD (HR, 0.80; 95% CI, 0.72-0.89; P < .001), year of HCT 2016-2018 (HR, 0.76; 95% CI, 0.68-0.85; P < .001). Acute GVHD, grade 3/4 (BM graft): disease (MDS [HR, 1.36; 95% CI, 1.06-1.75; P = .02], recipient age (40-55 years [HR, 0.75; 95% CI, 0.57-0.99; P = .04], and 55.1-65 years [HR, 0.72; 95% CI, 0.54-0.97; P = .03], NMA/RIC conditioning (HR, 1.37; 95% CI, 1.06-1.78; P = .02), DPB1 nonpermissive GVHD mismatch (HR, 1.30; 95% CI, 1.01-1.66; P = .04).
ALL, acute lymphoblastic leukemia; BM, bone marrow; CsA, cyclosporine; KPS, Karnofsky performance status; MDS, myelodysplastic neoplasms; NMA, nonmyeloablative conditioning; PB, peripheral blood; Ref, reference group; RIC, reduced intensity conditioning; TCD, T-cell depletion.
All outcomes are at 4 years, except acute GVHD (day 100).
Full models shown in supplemental Table 3.