Abstract 898

Chronic graft-versus-host disease (cGvHD) remains a major barrier to allogeneic (allo) hematopoietic cell transplant (HCT). Previous studies have identified several variables associated with high mortality in persons with cGvHD. The most consistent risk-factors for mortality are thrombocytopenia and the progressive type of cGvHD onset. We evaluated subject-, disease-, and transplant related variables at diagnosis of cGvHD to develop a risk score in 5343 patients with cGvHD. All patients received first allo-transplant for acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML) and myelodysplastic syndrome (MDS) between 1995 and 2004 and reported to CIBMTR. 10 variables were significantly correlated with cGvHD in multivariate analysis of overall survival and non-relapse mortality (NRM) and were used to build the risk score (Table 1). Variable-specific risk scores (VSRC) were constructed for each factor based on the relative risk (RR) of overall or NRM associated with each factor category. Scores were summed for each subject to assign an overall risk score (ORS). Risk groups (RG) of 1–6 were assigned based on the overall risk score. RG1: ORS 0–2, RG2: ORS 3–6, RG3: ORS 7–8, RG4: ORS 9–10, RG5: ORS: 11, RG6: ORS ≥ 12. Survival and NRM were significantly different between RGs (Figure 1 and Figure 2). Although this cGvHD risk score requires independent validation, knowledge of the above HCT factors and cGvHD-specific factors at the time of initial diagnosis provides important prognostic information for clinical care and clinical trial planning. Future analysis will validate this risk score in a more recent allo-transplant cohort assembled after 2005.

Table 1:
VariableOverall SurvivalNRMVSRC
 RR P RR P  
Recipient age (baseline: <10 years)  <0.0001  <0.0001 Age < 30: 0; 30–59: 1; > 60: 2 
10–19 1.35 0.0026 1.41 0.008  
20–29 1.31 0.0057 1.46 0.003  
30–39 1.41 0.0003 1.66 <0.0001  
40–49 1.53 <0.0001 1.90 <0.0001  
50–59 1.73 <0.0001 2.17 <0.0001  
> 60 2.18 <0.0001 2.75 <0.0001  
Prior Acute GVHD (baseline: no AGVHD)  <0.0001  <0.0001 No acute GVHD: 0; Prior acute GVHD: 1 
Grade I-II 1.23 0.0003 1.31 0.0001  
Grade III-IV 1.55 <0.0001 1.71 <0.0001  
Time from HCT to cGvHD (baseline: <5 mo)     > 5 mo: 0; < 5 mo: 1 
> 5mo 0.79 <0.0001 0.84 0.0016  
S. Bilirubin at cGvHD (baseline: < 1mg/dl)  <0.0001  <0.0001 Bilirubin ≤ 2: 0; Bilirubin > 2: 2 
1–2 mg/dl 1.11 0.0557 1.22 0.0035  
> 2 mg/dl 1.65 <0.0001 1.88 <0.0001  
KPS (cGvHD onset) (baseline: < 80)     KPS ≥ 80: 0 KPS <80: 1 
80–100 0.57 <0.0001 0.47 <0.0001  
Platelet count(cGvH onset) (baseline: < 100)     Platelets ≥ 100:0; Platelets < 100: 1 
> 100 × 10^9/L 0.64 <0.0001 0.53 <0.0001  
HLA group (baseline: HLA-identical sib)  <0.0001  <0.0001 HLA –identical sib, well-matched or partially matched URD:0; Other related or mismatched URD: 1 
Other related 1.38 0.0019 1.37 0.0137  
Well matched URD 1.03 0.6405 1.0 0.9863  
Partially matched URD 1.11 0.0931 1.17 0.0360  
Mismatched URD 1.37 <0.0001 1.51 <0.0001  
Disease status at HCT (Baseline: Early)  <0.0001  <0.0001 Early: 0; Intermediate: 1; Advanced: 2 
Intermediate 1.22 0.0001 0.99 0.0137  
Advanced 1.86 <0.0001 1.83 <0.0001  
GvHD prophylaxis (Baseline: T-cell depletion)  <0.0001  <0.0001 CSA + methotrexate +/− other: 0; Other categories: 1 
CSA + methotrexate+/− other 0.81 <0.0001 0.77 <0.0001  
Tacrolimus + methotrexate +/− other 1.12 0.1108 1.07 0.4099  
Sex match (Baseline: male to male) 1.94 <0.0001  <0.0001 Male to male, male to female, female to female: 0; Femal to male: 2 
Male to female 0.91 0.1096 0.89 0.1087  
Female to male 1.94 0.0009 1.25 0.0006  
Female to female 1.10 0.1203 1.15 0.0428  
VariableOverall SurvivalNRMVSRC
 RR P RR P  
Recipient age (baseline: <10 years)  <0.0001  <0.0001 Age < 30: 0; 30–59: 1; > 60: 2 
10–19 1.35 0.0026 1.41 0.008  
20–29 1.31 0.0057 1.46 0.003  
30–39 1.41 0.0003 1.66 <0.0001  
40–49 1.53 <0.0001 1.90 <0.0001  
50–59 1.73 <0.0001 2.17 <0.0001  
> 60 2.18 <0.0001 2.75 <0.0001  
Prior Acute GVHD (baseline: no AGVHD)  <0.0001  <0.0001 No acute GVHD: 0; Prior acute GVHD: 1 
Grade I-II 1.23 0.0003 1.31 0.0001  
Grade III-IV 1.55 <0.0001 1.71 <0.0001  
Time from HCT to cGvHD (baseline: <5 mo)     > 5 mo: 0; < 5 mo: 1 
> 5mo 0.79 <0.0001 0.84 0.0016  
S. Bilirubin at cGvHD (baseline: < 1mg/dl)  <0.0001  <0.0001 Bilirubin ≤ 2: 0; Bilirubin > 2: 2 
1–2 mg/dl 1.11 0.0557 1.22 0.0035  
> 2 mg/dl 1.65 <0.0001 1.88 <0.0001  
KPS (cGvHD onset) (baseline: < 80)     KPS ≥ 80: 0 KPS <80: 1 
80–100 0.57 <0.0001 0.47 <0.0001  
Platelet count(cGvH onset) (baseline: < 100)     Platelets ≥ 100:0; Platelets < 100: 1 
> 100 × 10^9/L 0.64 <0.0001 0.53 <0.0001  
HLA group (baseline: HLA-identical sib)  <0.0001  <0.0001 HLA –identical sib, well-matched or partially matched URD:0; Other related or mismatched URD: 1 
Other related 1.38 0.0019 1.37 0.0137  
Well matched URD 1.03 0.6405 1.0 0.9863  
Partially matched URD 1.11 0.0931 1.17 0.0360  
Mismatched URD 1.37 <0.0001 1.51 <0.0001  
Disease status at HCT (Baseline: Early)  <0.0001  <0.0001 Early: 0; Intermediate: 1; Advanced: 2 
Intermediate 1.22 0.0001 0.99 0.0137  
Advanced 1.86 <0.0001 1.83 <0.0001  
GvHD prophylaxis (Baseline: T-cell depletion)  <0.0001  <0.0001 CSA + methotrexate +/− other: 0; Other categories: 1 
CSA + methotrexate+/− other 0.81 <0.0001 0.77 <0.0001  
Tacrolimus + methotrexate +/− other 1.12 0.1108 1.07 0.4099  
Sex match (Baseline: male to male) 1.94 <0.0001  <0.0001 Male to male, male to female, female to female: 0; Femal to male: 2 
Male to female 0.91 0.1096 0.89 0.1087  
Female to male 1.94 0.0009 1.25 0.0006  
Female to female 1.10 0.1203 1.15 0.0428  
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Figure 1
Figure 1. Overall survival by cGvHD risk score
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Overall survival by cGvHD risk score

Figure 1
Figure 1. Overall survival by cGvHD risk score
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Overall survival by cGvHD risk score

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Figure 2
Figure 2. NRM by cGvHD risk score
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NRM by cGvHD risk score

Figure 2
Figure 2. NRM by cGvHD risk score
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NRM by cGvHD risk score

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Disclosures:

No relevant conflicts of interest to declare.

Topics:
graft-versus-host disease, chronic, allopurinol, bilirubin, graft-versus-host disease, acute, human leukocyte antigens, transplantation, methotrexate, acute lymphocytic leukemia, graft-versus-host disease, hematopoietic stem cell transplantation

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2010 by The American Society of Hematology
2010
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