Effects of disease stage, donor source, donor match, and conditioning regimen on survival and transplant-related outcomes
| . | Survival rate (95% CI) Month 48 . | CIF Estimate % (95% CI) Month 24* . | |||||||
|---|---|---|---|---|---|---|---|---|---|
| . | OS . | MFD-free . | Grade II-IV aGVHD . | Grade III-IV aGVHD . | Limited cGVHD . | Extensive cGVHD . | Overall cGVHD . | TRM . | Graft failure/rejection . |
| All | 20.5 (11.2-31.7) | 13.7 (6.3-23.9) | 13.3 (5.7-24.2) | 7.6 (2.4-17.0) | 16.7 (8.1-27.9) | 14.8 (6.3-26.6) | 17.0 (8.7-27.7) | ||
| Disease stage | |||||||||
| ED1 | 86.6 (53.9-96.7) | 67.8 (43.0-83.6) | 15.4 (4.7-31.9) | 11.5 (2.8-27.2) | 20.6 (7.2-38.8) | 8.2 (1.3-23.6) | 24.6 (9.6-43.2) | 4.3 (0.3-18.7) | 27.1 (11.7-45.2) |
| ED2 | 72.9 (27.6-92.5) | 61.7 (25.6-84.3) | 15.4 (2.2-40.1) | 7.7 (0.4-30.5) | NE (NE-NE) | 9.4 (0.4-35.9) | 9.4 (0.4-35.9) | 12.5 (0.5-44.5) | 15.4 (2.2-39.8) |
| ED | 81.9 (57.8-93.0) | 66.1 (46.3-80.0) | 15.4 (6.1-28.5) | 10.3 (3.2-22.2) | 13.6 (4.8-27.0) | 8.5 (2.1-20.8) | 19.3 (8.3-33.7) | 7.0 (1.1-20.5) | 23.2 (11.3-37.4) |
| AD | 53.0 (23.3-75.9) | 41.3 (17.3-63.9) | 25.6 (7.4-49.0) | 13.0 (1.9-34.8) | 12.4 (0.4-45.7) | 7.4 (0.4-29.6) | 7.4 (0.4-29.6) | 22.1 (4.9-47.1) | 6.3 (0.4-25.5) |
| ED vs AD | |||||||||
| P value | .008 | .015 | .423 | .815 | .539 | .949 | .304 | .094 | .153 |
| HR (95% CI) | 0.207 (0.058-0.743) | 0.348 (0.143-0.847) | 0.673 (0.190-2.388) | 0.935 (0.171-5.113) | 1.729 (0.200-14.910) | 0.890 (0.091-8.734) | 2.634 (0.323-21.502) | 0.214 (0.035-1.317) | 3.847 (0.487-30.372) |
| ED1 vs ED2 | |||||||||
| P value | .583 | .991 | .963 | .703 | .091 | .962 | .212 | .604 | .484 |
| HR (95% CI) | 0.581 (0.082-4.133) | 1.007 (0.295-3.441) | 1.096 (0.201-5.991) | 1.639 (0.170-15.775) | >1000 (0.000-> 1000) | 1.121 (0.102-12.374) | 4.472 (0.537-37.258) | 0.489 (0.031-7.819) | 1.743 (0.362-8.399) |
| Donor source† | |||||||||
| MRD | 67.3 (27.7-88.5) | 67.3 (27.7-88.5) | 16.7 (2.3-42.5) | 16.7 (2.3-42.5) | 10.1 (0.4-37.9) | 10.1 (0.4-37.9) | 20.2 (2.6-49.6) | 19.2 (2.5-47.6) | NE (NE-NE) |
| UR BM+PB | 76.0 (40.4-92.0) | 68.1 (37.5-86.0) | 15.8 (3.7-35.6) | 10.5 (1.6-29.1) | 16.8 (3.8-37.9) | 11.4 (1.7-31.5) | 22.2 (6.3-43.9) | 5.6 (0.3-23.1) | 15.8 (3.7-35.5) |
| UR UCB | 78.3 (46.5-92.5) | 49.5 (26.5-68.9) | 26.1 (10.2-45.3) | 17.4 (5.2-35.6) | 13.4 (3.1-31.4) | 4.3 (0.3-19.0) | 13.0 (3.0-30.5) | 24.1 (7.0-46.7) | 30.4 (13.2-49.8) |
| UR BM+PB+UCB | 78.4 (57.4-89.8) | 59.1 (41.2-73.2) | 21.4 (10.5-35.0) | 14.3 (5.7-26.7) | 15.3 (6.0-28.6) | 7.5 (1.9-18.5) | 17.1 (7.3-30.2) | 14.5 (5.2-28.4) | 23.8 (12.2-37.6) |
| UR BM+PB+UCB vs MRD | |||||||||
| P value | .660 | .348 | .827 | .713 | .732 | .827 | .857 | .769 | .068 |
| HR (95% CI) | 0.733 (0.183-2.940) | 1.796 (0.519-6.214) | 1.434 (0.310-6.642) | 0.910 (0.184-4.510) | 2.005 (0.240-16.780) | 1.103 (0.114-10.628) | 1.208 (0.249-5.850) | 0.787 (0.152-4.070) | >1000 (0.0-NE) |
| UR BM+PB vs MRD | |||||||||
| P value | .784 | .743 | .880 | .558 | .694 | .880 | .852 | .380 | .155 |
| HR (95% CI) | 1.252 (0.251-6.259) | 1.271 (0.302-5.358) | 0.938 (0.157-5.619) | 0.609 (0.086-4.321) | 1.866 (0.193-18.038) | 1.518 (0.138-16.751) | 1.463 (0.266-8.051) | 0.364 (0.033-4.063) | >1000 (0.0-NE) |
| UR UCB vs MRD | |||||||||
| P value | .713 | .162 | .637 | .910 | 842 | 0.572 | .624 | .784 | .039 |
| HR (95% CI) | 0.741 (0.149-3.682) | 2.441 (0.670-8.887) | 1.863 (0.375-9.251) | 1.153 (0.211-6.302) | 1.959 (0.202-18.986) | 0.761 (0.047-12.281) | 1.004 (0.166-6.068) | 1.266 (0.231-6.930) | >1000 (0.0-NE) |
| UR UCB vs UR BM+PB | |||||||||
| P value | .862 | .159 | .450 | .562 | .698 | .433 | .450 | .156 | .255 |
| HR (95% CI) | 1.153 (0.232-5.734) | 2.130 (0.726-6.247) | 1.941 (0.485-7.767) | 1.851 (0.339-10.108) | 0.954 (0.192-4.736) | 0.494 (0.045-5.464) | 0.703 (0.157-3.145) | 4.297 (0.480-38.503) | 2.128 (0.550-8.231) |
| Match status | |||||||||
| Matched | 80.9 (58.9-91.9) | 75.7 (54.8-87.9) | 14.0 (5.0-27.5) | 11.2 (3.5-24.0) | 11.9 (3.7-25.3) | 6.1 (1.0-18.0) | 18.0 (7.1-32.9) | 12.8 (3.9-27.3) | 11.3 (3.5-24.2) |
| Haplo+mismatched | 51.3 (21.0-75.2) | 30.0 (11.4-51.3) | 30.4 (13.0-50.0) | 17.4 (5.2-35.6) | 17.0 (3.6-39.0) | 10.3 (1.5-29.2) | 15.0 (3.3-34.9) | 19.5 (4.4-42.6) | 26.1 (10.3-45.2) |
| Haplo+mismatched vs Matched | |||||||||
| P value | .063 | .0001 | .157 | .5747 | .882 | .624 | .653 | .596 | .108 |
| HR (95% CI) | 2.949 (0.893-9.744) | 5.075 (2.035-12.66) | 2.769 (0.877-8.744) | 1.772 (0.443-7.088) | 1.531 (0.337-6.959) | 2.485 (0.342-18.039) | 0.969 (0.239-3.931) | 1.598 (0.355-7.192) | 2.720 (0.767-9.651) |
| Conditioning regimen | |||||||||
| Bu/Flu regimen | 81.6 (57.8-92.8) | 60.1 (40.3-75.1) | 6.4 (1.1-18.8) | 3.3 (0.2-14.6) | 9.9 (2.4-23.9) | 3.4 (0.2-15.3) | 13.4 (4.1-28.3) | 9.2 (1.4-26.0) | 25.1 (11.6-41.2) |
| Bu/Cy regimen | 64.7 (36.6-82.8) | 57.3 (31.2-76.6) | 36.0 (17.7-54.7) | 24.0 (9.5-42.1) | 19.2 (5.5-39.1) | 13.4 (3.1-31.2) | 21.9 (7.5-41.1) | 17.5 (5.3-35.7) | 8.0 (1.3-22.9) |
| Bu/Flu vs Bu/Cy | |||||||||
| P value | .365 | .649 | .006 | .020 | .476 | .173 | .431 | .342 | .089 |
| HR (95% CI) | 0.562 (0.158-1.993) | 1.231 (0.502-3.015) | 0.168 (0.036-0.778) | 0.138 (0.017-1.146) | 0.702 (0.156-3.151) | 0.257 (0.027-2.490) | 0.698 (0.186-2.617) | 0.459 (0.084-2.511) | 3.492 (0.741-16.452) |
| . | Survival rate (95% CI) Month 48 . | CIF Estimate % (95% CI) Month 24* . | |||||||
|---|---|---|---|---|---|---|---|---|---|
| . | OS . | MFD-free . | Grade II-IV aGVHD . | Grade III-IV aGVHD . | Limited cGVHD . | Extensive cGVHD . | Overall cGVHD . | TRM . | Graft failure/rejection . |
| All | 20.5 (11.2-31.7) | 13.7 (6.3-23.9) | 13.3 (5.7-24.2) | 7.6 (2.4-17.0) | 16.7 (8.1-27.9) | 14.8 (6.3-26.6) | 17.0 (8.7-27.7) | ||
| Disease stage | |||||||||
| ED1 | 86.6 (53.9-96.7) | 67.8 (43.0-83.6) | 15.4 (4.7-31.9) | 11.5 (2.8-27.2) | 20.6 (7.2-38.8) | 8.2 (1.3-23.6) | 24.6 (9.6-43.2) | 4.3 (0.3-18.7) | 27.1 (11.7-45.2) |
| ED2 | 72.9 (27.6-92.5) | 61.7 (25.6-84.3) | 15.4 (2.2-40.1) | 7.7 (0.4-30.5) | NE (NE-NE) | 9.4 (0.4-35.9) | 9.4 (0.4-35.9) | 12.5 (0.5-44.5) | 15.4 (2.2-39.8) |
| ED | 81.9 (57.8-93.0) | 66.1 (46.3-80.0) | 15.4 (6.1-28.5) | 10.3 (3.2-22.2) | 13.6 (4.8-27.0) | 8.5 (2.1-20.8) | 19.3 (8.3-33.7) | 7.0 (1.1-20.5) | 23.2 (11.3-37.4) |
| AD | 53.0 (23.3-75.9) | 41.3 (17.3-63.9) | 25.6 (7.4-49.0) | 13.0 (1.9-34.8) | 12.4 (0.4-45.7) | 7.4 (0.4-29.6) | 7.4 (0.4-29.6) | 22.1 (4.9-47.1) | 6.3 (0.4-25.5) |
| ED vs AD | |||||||||
| P value | .008 | .015 | .423 | .815 | .539 | .949 | .304 | .094 | .153 |
| HR (95% CI) | 0.207 (0.058-0.743) | 0.348 (0.143-0.847) | 0.673 (0.190-2.388) | 0.935 (0.171-5.113) | 1.729 (0.200-14.910) | 0.890 (0.091-8.734) | 2.634 (0.323-21.502) | 0.214 (0.035-1.317) | 3.847 (0.487-30.372) |
| ED1 vs ED2 | |||||||||
| P value | .583 | .991 | .963 | .703 | .091 | .962 | .212 | .604 | .484 |
| HR (95% CI) | 0.581 (0.082-4.133) | 1.007 (0.295-3.441) | 1.096 (0.201-5.991) | 1.639 (0.170-15.775) | >1000 (0.000-> 1000) | 1.121 (0.102-12.374) | 4.472 (0.537-37.258) | 0.489 (0.031-7.819) | 1.743 (0.362-8.399) |
| Donor source† | |||||||||
| MRD | 67.3 (27.7-88.5) | 67.3 (27.7-88.5) | 16.7 (2.3-42.5) | 16.7 (2.3-42.5) | 10.1 (0.4-37.9) | 10.1 (0.4-37.9) | 20.2 (2.6-49.6) | 19.2 (2.5-47.6) | NE (NE-NE) |
| UR BM+PB | 76.0 (40.4-92.0) | 68.1 (37.5-86.0) | 15.8 (3.7-35.6) | 10.5 (1.6-29.1) | 16.8 (3.8-37.9) | 11.4 (1.7-31.5) | 22.2 (6.3-43.9) | 5.6 (0.3-23.1) | 15.8 (3.7-35.5) |
| UR UCB | 78.3 (46.5-92.5) | 49.5 (26.5-68.9) | 26.1 (10.2-45.3) | 17.4 (5.2-35.6) | 13.4 (3.1-31.4) | 4.3 (0.3-19.0) | 13.0 (3.0-30.5) | 24.1 (7.0-46.7) | 30.4 (13.2-49.8) |
| UR BM+PB+UCB | 78.4 (57.4-89.8) | 59.1 (41.2-73.2) | 21.4 (10.5-35.0) | 14.3 (5.7-26.7) | 15.3 (6.0-28.6) | 7.5 (1.9-18.5) | 17.1 (7.3-30.2) | 14.5 (5.2-28.4) | 23.8 (12.2-37.6) |
| UR BM+PB+UCB vs MRD | |||||||||
| P value | .660 | .348 | .827 | .713 | .732 | .827 | .857 | .769 | .068 |
| HR (95% CI) | 0.733 (0.183-2.940) | 1.796 (0.519-6.214) | 1.434 (0.310-6.642) | 0.910 (0.184-4.510) | 2.005 (0.240-16.780) | 1.103 (0.114-10.628) | 1.208 (0.249-5.850) | 0.787 (0.152-4.070) | >1000 (0.0-NE) |
| UR BM+PB vs MRD | |||||||||
| P value | .784 | .743 | .880 | .558 | .694 | .880 | .852 | .380 | .155 |
| HR (95% CI) | 1.252 (0.251-6.259) | 1.271 (0.302-5.358) | 0.938 (0.157-5.619) | 0.609 (0.086-4.321) | 1.866 (0.193-18.038) | 1.518 (0.138-16.751) | 1.463 (0.266-8.051) | 0.364 (0.033-4.063) | >1000 (0.0-NE) |
| UR UCB vs MRD | |||||||||
| P value | .713 | .162 | .637 | .910 | 842 | 0.572 | .624 | .784 | .039 |
| HR (95% CI) | 0.741 (0.149-3.682) | 2.441 (0.670-8.887) | 1.863 (0.375-9.251) | 1.153 (0.211-6.302) | 1.959 (0.202-18.986) | 0.761 (0.047-12.281) | 1.004 (0.166-6.068) | 1.266 (0.231-6.930) | >1000 (0.0-NE) |
| UR UCB vs UR BM+PB | |||||||||
| P value | .862 | .159 | .450 | .562 | .698 | .433 | .450 | .156 | .255 |
| HR (95% CI) | 1.153 (0.232-5.734) | 2.130 (0.726-6.247) | 1.941 (0.485-7.767) | 1.851 (0.339-10.108) | 0.954 (0.192-4.736) | 0.494 (0.045-5.464) | 0.703 (0.157-3.145) | 4.297 (0.480-38.503) | 2.128 (0.550-8.231) |
| Match status | |||||||||
| Matched | 80.9 (58.9-91.9) | 75.7 (54.8-87.9) | 14.0 (5.0-27.5) | 11.2 (3.5-24.0) | 11.9 (3.7-25.3) | 6.1 (1.0-18.0) | 18.0 (7.1-32.9) | 12.8 (3.9-27.3) | 11.3 (3.5-24.2) |
| Haplo+mismatched | 51.3 (21.0-75.2) | 30.0 (11.4-51.3) | 30.4 (13.0-50.0) | 17.4 (5.2-35.6) | 17.0 (3.6-39.0) | 10.3 (1.5-29.2) | 15.0 (3.3-34.9) | 19.5 (4.4-42.6) | 26.1 (10.3-45.2) |
| Haplo+mismatched vs Matched | |||||||||
| P value | .063 | .0001 | .157 | .5747 | .882 | .624 | .653 | .596 | .108 |
| HR (95% CI) | 2.949 (0.893-9.744) | 5.075 (2.035-12.66) | 2.769 (0.877-8.744) | 1.772 (0.443-7.088) | 1.531 (0.337-6.959) | 2.485 (0.342-18.039) | 0.969 (0.239-3.931) | 1.598 (0.355-7.192) | 2.720 (0.767-9.651) |
| Conditioning regimen | |||||||||
| Bu/Flu regimen | 81.6 (57.8-92.8) | 60.1 (40.3-75.1) | 6.4 (1.1-18.8) | 3.3 (0.2-14.6) | 9.9 (2.4-23.9) | 3.4 (0.2-15.3) | 13.4 (4.1-28.3) | 9.2 (1.4-26.0) | 25.1 (11.6-41.2) |
| Bu/Cy regimen | 64.7 (36.6-82.8) | 57.3 (31.2-76.6) | 36.0 (17.7-54.7) | 24.0 (9.5-42.1) | 19.2 (5.5-39.1) | 13.4 (3.1-31.2) | 21.9 (7.5-41.1) | 17.5 (5.3-35.7) | 8.0 (1.3-22.9) |
| Bu/Flu vs Bu/Cy | |||||||||
| P value | .365 | .649 | .006 | .020 | .476 | .173 | .431 | .342 | .089 |
| HR (95% CI) | 0.562 (0.158-1.993) | 1.231 (0.502-3.015) | 0.168 (0.036-0.778) | 0.138 (0.017-1.146) | 0.702 (0.156-3.151) | 0.257 (0.027-2.490) | 0.698 (0.186-2.617) | 0.459 (0.084-2.511) | 3.492 (0.741-16.452) |
Deaths, MFDs, and second allo-HSC infusions are considered events for MFD-free survival outcome. MFDs included loss of communication, cortical blindness, tube feeding dependence, total incontinence, wheelchair dependence, and complete loss of voluntary movement. Patients who did not experience any event are censored at the time of the last MFD assessment when they are MFD-free. Survival rates estimated using Kaplan-Meier analysis. HR (95% CI) for survival rates calculated by Cox proportional hazards model. P values for survival analyses from log-rank test; underlining and italics denote P values < 0.05 and 0.05-0.1, respectively. Bold numbers indicate a P value that is statistically significant.
HR (95% CI) for cumulative incidence functions (CIF) estimates from a cause-specific hazard model. P values are calculated using competing risks analysis calculated by Gray’s test.
NE, not estimable; UR, unrelated.
Same as at month 48.
Haploidentical category (donor source) = 5 patients had allo-HSCT using haploidentical donors, but all had <24 months of follow-up after allo-HSCT; therefore, data as of month 24 or month 48 were not available.