Abstract
Anti-leukemia effects of allotransplants are largely mediated by immune mechanisms collectively termed graft-versus-leukemia (GvL). We postulated that allotransplants from HLA-matched unrelated donors (URD) have greater GvL activity than similar transplants from HLA-identical siblings because of greater genetic-disparity between donor and recipient. We tested this hypothesis in 4099 adult recipients of HLA-matched sibling (N= 3158) or 8/8 HLA-allele-matched URD (N= 941) transplants for acute leukemia (AML and ALL) and chronic myeloid leukemia (CML) receiving conventional transplants between 1995–2004 and reported to CIBMTR. Relapse, transplant-related mortality (TRM) and leukemia-free survival (LFS) were compared between the cohorts. Contrary to our hypothesis, relapse rates at 5 y were similar in patients receiving sibling and URD transplants. More TRM was seen in URD cohort in early AML [sibs 24% (20–27%) versus URD 40% (31–50%), p=0.001], advanced ALL or AML [sibs 31% (25–36%) versus URD 44% (35–53%), p= 0.01] and early CML [sibs 31% (28–33%) versus 38% (32–44%), p=0.02]. LFS was superior with sibling donors in early- and advanced- AML and CML. These data indicate comparable GvL-activity of HLA matched URD and HLA-identical sibling transplants in AML, ALL and CML receiving conventional transplants despite greater genetic disparity.
| Early Disease (1stremission or 1st chronic phase) . | |||
|---|---|---|---|
| Outcome at 5 years . | Sibling donor . | URD . | P . |
| AML (N= 878) | 760 | 118 | |
| Relapse | 15 (13–18)% | 22 (15–30)% | 0.1 |
| LFS | 61 (57–65)% | 38 (28–48)% | <0.001 |
| ALL (N= 333) | 271 | 62 | |
| Relapse | 23 (18–29)% | 15 (7–25)% | 0.13 |
| LFS | 46 (39–53)% | 42 (29–55)% | 0.6 |
| CML (N=1443) | 1152 | 291 | |
| Relapse | 6 (5–8)% | 5 (3–8)% | 0.5 |
| LFS | 63 (60–66)% | 57 (51–63)% | 0.06 |
| Intermediate Disease (2nd or subsequent remission or accelerated phase) | |||
| AML (N= 268) | 180 | 88 | |
| Relapse | 22 (16–29)% | 21 (13–30)% | 0.8 |
| LFS | 48 (40–56)% | 41 (30–52)% | 0.3 |
| ALL (N= 172) | 111 | 61 | |
| Relapse | 32 (24–42)% | 36 (24–48)% | 0.7 |
| LFS | 27 (18–36)% | 24 (14–37)% | 0.8 |
| CML (N=263) | 173 | 90 | |
| Relapse | 22 (15–28)% | 16 (9–24)% | 0.5 |
| LFS | 36 (29–44)% | 35 (26–46)% | 0.9 |
| Advanced Disease (Not in remission or blast phase) | |||
| AML (N= 423) | 294 | 129 | |
| Relapse | 46 (40–52)% | 43 (34–51)% | 0.6 |
| LFS | 23 (18–29)% | 13 (8–20)% | 0.01 |
| ALL (N= 152) | 88 | 64 | |
| Relapse | 52 (42–63)% | 48 (35–60)% | 0.6 |
| LFS | 10 (4–18)% | 5 (1–12)% | 0.2 |
| CML (N=76) | 49 | 27 | |
| Relapse | 35 (23–49)% | 39 (20–60)% | 0.8 |
| LFS | 21 (11–35)% | 0 | <0.001 |
| Early Disease (1stremission or 1st chronic phase) . | |||
|---|---|---|---|
| Outcome at 5 years . | Sibling donor . | URD . | P . |
| AML (N= 878) | 760 | 118 | |
| Relapse | 15 (13–18)% | 22 (15–30)% | 0.1 |
| LFS | 61 (57–65)% | 38 (28–48)% | <0.001 |
| ALL (N= 333) | 271 | 62 | |
| Relapse | 23 (18–29)% | 15 (7–25)% | 0.13 |
| LFS | 46 (39–53)% | 42 (29–55)% | 0.6 |
| CML (N=1443) | 1152 | 291 | |
| Relapse | 6 (5–8)% | 5 (3–8)% | 0.5 |
| LFS | 63 (60–66)% | 57 (51–63)% | 0.06 |
| Intermediate Disease (2nd or subsequent remission or accelerated phase) | |||
| AML (N= 268) | 180 | 88 | |
| Relapse | 22 (16–29)% | 21 (13–30)% | 0.8 |
| LFS | 48 (40–56)% | 41 (30–52)% | 0.3 |
| ALL (N= 172) | 111 | 61 | |
| Relapse | 32 (24–42)% | 36 (24–48)% | 0.7 |
| LFS | 27 (18–36)% | 24 (14–37)% | 0.8 |
| CML (N=263) | 173 | 90 | |
| Relapse | 22 (15–28)% | 16 (9–24)% | 0.5 |
| LFS | 36 (29–44)% | 35 (26–46)% | 0.9 |
| Advanced Disease (Not in remission or blast phase) | |||
| AML (N= 423) | 294 | 129 | |
| Relapse | 46 (40–52)% | 43 (34–51)% | 0.6 |
| LFS | 23 (18–29)% | 13 (8–20)% | 0.01 |
| ALL (N= 152) | 88 | 64 | |
| Relapse | 52 (42–63)% | 48 (35–60)% | 0.6 |
| LFS | 10 (4–18)% | 5 (1–12)% | 0.2 |
| CML (N=76) | 49 | 27 | |
| Relapse | 35 (23–49)% | 39 (20–60)% | 0.8 |
| LFS | 21 (11–35)% | 0 | <0.001 |
Author notes
Disclosure: No relevant conflicts of interest to declare.
