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 yearsSibling donorURDP
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)% <0.001 
Early Disease (1stremission or 1st chronic phase)
Outcome at 5 yearsSibling donorURDP
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)% <0.001 

Author notes

Disclosure: No relevant conflicts of interest to declare.