Table 3

Risk factors associated with treatment failure

FactorNUnivariateMultivariate
Hazard ratio (95% CI)PHazard ratio (95% CI)P
Patient age at initial treatment      
 0-39 97 1.00 (reference)  1.00 (reference)  
 40-49 77 1.05 (0.71-1.55) .81 1.00 (reference)  
 50-59 125 1.07 (0.77-1.49) .70 1.00 (reference)  
 ≥60 101 1.43 (1.01-2.01) .04 1.48 (1.13-1.95) .004 
Female donor to male recipient 108 1.03 (0.79-1.35) .81  
High-risk disease at transplantation 264 1.00 (0.78-1.29) .99  
Conditioning regimen     
 High dose without TBI 137 1.00 (reference)   
 High dose with TBI 81 1.38 (0.97-1.95) .07  
 Reduced intensity 182 1.46 (1.10-1.94) .009  
Graft source     
 Bone marrow 46 1.00 (reference)   
 Mobilized blood cells 332 1.22 (0.79-1.87) .37  
 Cord blood 22 0.90 (0.44-1.85) .78  
Donor and HLA type     
 HLA-matched related 147 1.00 (reference)   
 HLA-matched unrelated 155 1.12 (0.85-1.47) .44  
 HLA-mismatched 98 0.97 (0.70-1.33) .84  
Time from transplantation to initial systemic treatment     
 <6 mo 166 1.00 (reference)  1.46 (1.05-2.03) .02 
 6 to <12 mo 157 0.99 (0.76-1.29) .92 1.46 (1.05-2.03)  
 12 to <24 mo 66 0.74 (0.52-1.07) .11 1.00 (reference)  
 ≥24 mo 11 0.31 (0.10-0.99) .05 1.00 (reference)  
Presence of involvement at initial treatment     
 Skin 302 1.13 (0.84-1.51) .43  
 Eyes 115 1.18 (0.91-1.54) .21  
 Mouth 363 1.02 (0.66-1.56) .94  
 Liver 175 0.80 (0.63-1.03) .08  
 Gastrointestinal tract     
  No involvement 241 1.00 (reference)   
  Upper only 78 1.19 (0.87-1.63) .27  
  Any lower 81 1.35 (1.00-1.83) .05  
 Lungs 14 1.34 (0.71-2.53) .36  
 Joint or fascia 54 0.75 (0.51-1.10) .14  
 Genital tract 29 0.80 (0.49-1.31) .38  
Score 3 in the gastrointestinal tract, liver, or lungs 54 1.43 (1.02-2.01) .04 1.43 (1.02-2.02) .04 
No. of sites involved at initial treatment     
 1 or 2 136 1.00 (reference)   
 3 149 0.80 (0.59-1.07) .13  
 ≥4 115 1.10 (0.82-1.49) .53  
NIH global score at initial treatment     
 Moderate 228 1.00 (reference)   
 Severe 172 1.09 (0.86-1.40) .47  
Subcategory of chronic GVHD     
 Classic 45 1.00 (reference)   
 Overlap 355 1.11 (0.74-1.67) .61  
Karnofsky score <80% 140 1.32 (1.03-1.70) .03 1.29 (1.01-1.67) .04 
Thrombocytopenia at initial treatment 105 1.16 (0.89-1.53) .28  
Hyperbilirubinemia at initial treatment 16 1.13 (0.62-2.06) .70  
Progressive onset 39 0.79 (0.52-1.21) .28  
Prior grades II-IV acute GVHD 296 1.10 (0.82-1.46) .53  
Prednisone dose before onset of initial treatment     
 None 299 1.00 (reference)   
 <0.5 mg/kg daily 61 1.28 (0.92-1.77) .14  
 ≥0.5 mg/kg daily 40 0.92 (0.61-1.38) .67  
Initial treatment of chronic GVHD     
 Prednisone ± calcineurin inhibitor 203 1.00 (reference)   
 Prednisone + others* 136 0.82 (0.62-1.07) .15  
 Treatment without prednisone 61 0.99 (0.69-1.40) .94  
Prednisone dose used for initial treatment     
 No prednisone 61 1.00 (reference)   
 <0.5 mg/kg/daily 38 1.05 (0.64-1.72) .85  
 ≥0.5 but <1.0 mg/kg/daily 105 0.87 (0.59-1.29) .49  
 ≥1.0 mg/kg/daily 196 0.95 (0.67-1.35) .78  
Number of agents used for initial treatment     
 1 84 1.18 (0.86-1.60) .31  
 2 216 1.00 (reference)   
 ≥3 100 0.88 (0.66-1.18) .40  
FactorNUnivariateMultivariate
Hazard ratio (95% CI)PHazard ratio (95% CI)P
Patient age at initial treatment      
 0-39 97 1.00 (reference)  1.00 (reference)  
 40-49 77 1.05 (0.71-1.55) .81 1.00 (reference)  
 50-59 125 1.07 (0.77-1.49) .70 1.00 (reference)  
 ≥60 101 1.43 (1.01-2.01) .04 1.48 (1.13-1.95) .004 
Female donor to male recipient 108 1.03 (0.79-1.35) .81  
High-risk disease at transplantation 264 1.00 (0.78-1.29) .99  
Conditioning regimen     
 High dose without TBI 137 1.00 (reference)   
 High dose with TBI 81 1.38 (0.97-1.95) .07  
 Reduced intensity 182 1.46 (1.10-1.94) .009  
Graft source     
 Bone marrow 46 1.00 (reference)   
 Mobilized blood cells 332 1.22 (0.79-1.87) .37  
 Cord blood 22 0.90 (0.44-1.85) .78  
Donor and HLA type     
 HLA-matched related 147 1.00 (reference)   
 HLA-matched unrelated 155 1.12 (0.85-1.47) .44  
 HLA-mismatched 98 0.97 (0.70-1.33) .84  
Time from transplantation to initial systemic treatment     
 <6 mo 166 1.00 (reference)  1.46 (1.05-2.03) .02 
 6 to <12 mo 157 0.99 (0.76-1.29) .92 1.46 (1.05-2.03)  
 12 to <24 mo 66 0.74 (0.52-1.07) .11 1.00 (reference)  
 ≥24 mo 11 0.31 (0.10-0.99) .05 1.00 (reference)  
Presence of involvement at initial treatment     
 Skin 302 1.13 (0.84-1.51) .43  
 Eyes 115 1.18 (0.91-1.54) .21  
 Mouth 363 1.02 (0.66-1.56) .94  
 Liver 175 0.80 (0.63-1.03) .08  
 Gastrointestinal tract     
  No involvement 241 1.00 (reference)   
  Upper only 78 1.19 (0.87-1.63) .27  
  Any lower 81 1.35 (1.00-1.83) .05  
 Lungs 14 1.34 (0.71-2.53) .36  
 Joint or fascia 54 0.75 (0.51-1.10) .14  
 Genital tract 29 0.80 (0.49-1.31) .38  
Score 3 in the gastrointestinal tract, liver, or lungs 54 1.43 (1.02-2.01) .04 1.43 (1.02-2.02) .04 
No. of sites involved at initial treatment     
 1 or 2 136 1.00 (reference)   
 3 149 0.80 (0.59-1.07) .13  
 ≥4 115 1.10 (0.82-1.49) .53  
NIH global score at initial treatment     
 Moderate 228 1.00 (reference)   
 Severe 172 1.09 (0.86-1.40) .47  
Subcategory of chronic GVHD     
 Classic 45 1.00 (reference)   
 Overlap 355 1.11 (0.74-1.67) .61  
Karnofsky score <80% 140 1.32 (1.03-1.70) .03 1.29 (1.01-1.67) .04 
Thrombocytopenia at initial treatment 105 1.16 (0.89-1.53) .28  
Hyperbilirubinemia at initial treatment 16 1.13 (0.62-2.06) .70  
Progressive onset 39 0.79 (0.52-1.21) .28  
Prior grades II-IV acute GVHD 296 1.10 (0.82-1.46) .53  
Prednisone dose before onset of initial treatment     
 None 299 1.00 (reference)   
 <0.5 mg/kg daily 61 1.28 (0.92-1.77) .14  
 ≥0.5 mg/kg daily 40 0.92 (0.61-1.38) .67  
Initial treatment of chronic GVHD     
 Prednisone ± calcineurin inhibitor 203 1.00 (reference)   
 Prednisone + others* 136 0.82 (0.62-1.07) .15  
 Treatment without prednisone 61 0.99 (0.69-1.40) .94  
Prednisone dose used for initial treatment     
 No prednisone 61 1.00 (reference)   
 <0.5 mg/kg/daily 38 1.05 (0.64-1.72) .85  
 ≥0.5 but <1.0 mg/kg/daily 105 0.87 (0.59-1.29) .49  
 ≥1.0 mg/kg/daily 196 0.95 (0.67-1.35) .78  
Number of agents used for initial treatment     
 1 84 1.18 (0.86-1.60) .31  
 2 216 1.00 (reference)   
 ≥3 100 0.88 (0.66-1.18) .40  

Treatment failure was defined by the onset of second-line systemic treatment, nonrelapse death, or recurrent malignancy during first-line treatment. TBI, total body irradiation.

*

Other treatments include extracorporeal photopheresis, rituximab, thalidomide, alemtuzumab, infliximab, antithymocyte globulin, and methotrexate. Risk of treatment failure did not differ statistically according to any individual agent.

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