Abstract 897

Recent changes in allogeneic hematopoietic cell transplantation (HCT) including increased use of reduced-intensity conditioning, peripheral blood cells as the graft source (PB) and unrelated donors (URD) warrant re-evaluation of risk factors for acute graft-versus-host disease (aGVHD) and its impact on overall survival (OS). Risk factors for these outcomes were analyzed using more recent data from CIBMTR observational database.

Methods:

The cohort included adult patients ≥ 20 y transplanted from an HLA-identical sibling (SD) (n=3191) or URD (N=2370) for acute myelogenous leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), or myelodsyplastic syndrome (MDS) using a T-cell replete graft from 1999–2005. Six groups were created to evaluate the impact of conditioning [(myeloablative (MA) and reduced-intensity or non-myeloablative (RIC)], total-body irradiation (TBI) and graft source [(bone marrow (BM) or PB] as follows: MA+TBI+PB (group 1), MA+TBI+BM (group 2) MA+ no TBI+PB (group 3), MA+ no-TBI+BM (group 4), RIC+PB (group 5) and RIC+BM (group 6). Separate analyses were performed for SD and URD. IBMTR grade was used to classify aGVHD. A p-value of ≤ 0.01 was considered significant.

Results:

Among the SD cohort, the probability of aGVHD grade B-D and grade C-D at 100 days was 39% (95% CI, 37–41%) and 16% (95% CI, 14–17%). In multivariate analyses, non-TBI based MA regimens with a BM graft (group 4), RIC conditioning with PB (group 5) and tacrolimus plus methotrexate aGVHD prophylaxis were associated with lower odds ratio of grade B-D aGVHD (Table 1). The probability of OS was 51% (95% CI: 49–53%) at 3 y and 46% (95% CI: 44–49%) at 5 y. In multivariate analyses, grade B-D aGVHD was associated with a higher risk of death. Other independent risk factors for OS are shown in Table 2. Among the URD cohort, the probability of aGVHD grade B-D and C-D at 100 days was 59% (95%, CI 57–61%) and 32% (30-34%). In multivariate analysis, BM with MA (TBI and no TBI) or RIC conditioning (groups 2, 4 and 6) were significantly associated with lower odds ratio of grade B-D aGVHD (Table 1). Other independent risk factors included a diagnosis of CML. HCT from a 7/8 HLA-mismatched URD showed a trend for higher incidence of aGVHD (p=0.02). The probability of OS was 38% (95% CI: 35–40%) at 3 y and 33% (95% CI: 31–35%) at 5 y. In multivariate analysis, grade B-D aGVHD was associated with a higher mortality. Table 2 shows other independent risk factors for OS.

Conclusion:

Intensity of the conditioning regimen, TBI and the graft source has a combined effect on the risk of aGVHD. In both SD and URD cohorts, BM with MA, non-TBI regimens were associated with lower risk of aGVHD. In URD cohort, BM after a RIC also was associated with a reduced risk of aGVHD. Modulation of these risk factors is needed to reduce acute GVHD incidence and death after allogeneic transplantation.

Table 1:

Risk Factors for grade B-D aGVHD

SDURD
VariableNRR95% CIPNOR95% CIP
Group 1: MA + TBI + PB(reference) 709 1.0    1.0   
Group 2: MA + TBI + BM 245 0.94 0.70–1.27 0.69 733 0.71 0.5–0.91 0.006 
Group3: MA + no TBI + PBSC 1017 0.97 0.80–1.18 0.78 350 0.87 0.65–1.16 0.34 
Group 4: MA + no TBI + BM 492 0.56 0.44–0.71 <0.0001 265 0.55 0.40–0.75 0.0001 
Group 5: RIC + PBSC 622 0.70 0.56–0.88 0.002 405 0.75 0.57–1.00 0.05 
Group 6: RIC + BM 67 0.90 0.54–1.49 0.67 83 0.47 0.29–0.76 0.002 
GvHD prophylaxis (baseline: CSA+ methotrexate +/− others):SD only 2645 1.0       
Tacrolimus+ methotrextae+/− others 484 0.65 0.53–0.80 <0.0001     
Disease (baseline ALL):URD only     446 1.0   
CML     463 1.51 1.14–1.99 0.004 
HLA match (baseline 8/8): URD only     1532 1.0  0.03 
7/8 matched     614 1.27 1.05–1.54 0.02 
SDURD
VariableNRR95% CIPNOR95% CIP
Group 1: MA + TBI + PB(reference) 709 1.0    1.0   
Group 2: MA + TBI + BM 245 0.94 0.70–1.27 0.69 733 0.71 0.5–0.91 0.006 
Group3: MA + no TBI + PBSC 1017 0.97 0.80–1.18 0.78 350 0.87 0.65–1.16 0.34 
Group 4: MA + no TBI + BM 492 0.56 0.44–0.71 <0.0001 265 0.55 0.40–0.75 0.0001 
Group 5: RIC + PBSC 622 0.70 0.56–0.88 0.002 405 0.75 0.57–1.00 0.05 
Group 6: RIC + BM 67 0.90 0.54–1.49 0.67 83 0.47 0.29–0.76 0.002 
GvHD prophylaxis (baseline: CSA+ methotrexate +/− others):SD only 2645 1.0       
Tacrolimus+ methotrextae+/− others 484 0.65 0.53–0.80 <0.0001     
Disease (baseline ALL):URD only     446 1.0   
CML     463 1.51 1.14–1.99 0.004 
HLA match (baseline 8/8): URD only     1532 1.0  0.03 
7/8 matched     614 1.27 1.05–1.54 0.02 
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Table 2:

Risk factors for OS

SDURD
VariableNRR95% CIPNOR95% CIP
Recipient age         
40–49 866 1.28 1.12–1.46 0.0004 644 1.24 1.09–1.42 0.001 
50+ 944 1.59 1.39–1.82 <0.0001 786 1.29 1.13–1.46 0.0001 
Donor age: URD only         
> 30     1669 1.19 1.07–1.34 0.002 
Karnofsky score(KPS)         
80–100 2789 0.52 0.45–0.61 <0.0001 1906 0.68 0.58–0.81 <0.0001 
Diagnosis: SD only         
AML 1362 0.68 0.59–0.80 <0.0001     
CML 828 0.58 0.48–0.70 <0.0001     
MDS 457 0.53 0.43–0.66 <0.0001     
Disease status at transplant         
Intermediate 520 1.51 1.31–1.75 <0.0001 568 1.28 1.11–1.47 0.0007 
Advanced 666 2.23 1.95–2.55 <0.0001 707 2.15 1.88–2.46 <0.0001 
Sex mismatch (D/R): SD only         
F/M 746 1.25 1.11–1.40 0.0002     
Donor: Recipient CMV serostatus: URD only         
NP/PN/PP     1586 1.19 1.06–1.33 0.003 
HLA-match: URD only         
7/8 matched     614 1.23 1.09–1.38 0.0006 
< 6/8 matched     224 1.68 1.42–1.98 <0.0001 
SDURD
VariableNRR95% CIPNOR95% CIP
Recipient age         
40–49 866 1.28 1.12–1.46 0.0004 644 1.24 1.09–1.42 0.001 
50+ 944 1.59 1.39–1.82 <0.0001 786 1.29 1.13–1.46 0.0001 
Donor age: URD only         
> 30     1669 1.19 1.07–1.34 0.002 
Karnofsky score(KPS)         
80–100 2789 0.52 0.45–0.61 <0.0001 1906 0.68 0.58–0.81 <0.0001 
Diagnosis: SD only         
AML 1362 0.68 0.59–0.80 <0.0001     
CML 828 0.58 0.48–0.70 <0.0001     
MDS 457 0.53 0.43–0.66 <0.0001     
Disease status at transplant         
Intermediate 520 1.51 1.31–1.75 <0.0001 568 1.28 1.11–1.47 0.0007 
Advanced 666 2.23 1.95–2.55 <0.0001 707 2.15 1.88–2.46 <0.0001 
Sex mismatch (D/R): SD only         
F/M 746 1.25 1.11–1.40 0.0002     
Donor: Recipient CMV serostatus: URD only         
NP/PN/PP     1586 1.19 1.06–1.33 0.003 
HLA-match: URD only         
7/8 matched     614 1.23 1.09–1.38 0.0006 
< 6/8 matched     224 1.68 1.42–1.98 <0.0001 
View Large
Disclosures:

No relevant conflicts of interest to declare.

Topics:
donors, graft-versus-host disease, acute, hematopoietic stem cell transplantation, relationship - sibling, risk factors, tissue transplants, human leukocyte antigens, methotrexate, acute lymphocytic leukemia, graft-versus-host disease

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2010 by The American Society of Hematology
2010
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