Reduced intensity conditioning regimens and improvements in supportive care have allowed for the expansion of allogeneic stem cell transplantation to those previously ineligble. However, such patients remain at significant risk for regimen related toxicity. We examined whether clinical predictors that influence toxicity after standard chemotherapy, such as age, comorbidity and functional status similarly predict increased transplant related mortality (TRM) and decreased survival after a RIST with in-vivo T-cell depletion. We analyzed 81 consecutive patients on a single protocol with high-risk and refractory hematologic malignancies transplanted at our institution from 2002 to 2004. The conditioning regimen consisted of fludarabine 30 mg/m2/d (D-7 to D-3), Campath-1H 20 mg/d (D-7 to D-3), and melphalan 140 mg/m2 (D-2) with tacrolimus given for post-transplant immunosuppression. Comorbidity was scored from a retrospective chart review using the Charlson Comorbidity Index (CC) and the Kaplan-Feinstein scale (KF). Eastern Cooperative Oncology Group performance status (PS) and age at transplant were tabulated. TRM was defined as any death occurring without disease progression. Median age was 51 years (range 17–68). Fifty-five percent had HLA-identical sibling donors, 5% had mismatched related donors, 35% had matched unrelated donors and 5% had mismatched unrelated donors. KF served as a more sensitive indicator of comorbidity than CC. Fifty-three percent of patients scored at least one point for a comorbid condition by KF, as opposed to 25% by CC (P<.001 by Chi square), and 28% scored at least 2 points by KF versus 8% by CC (P<.001 by Chi square). PS was 0, 1, and >1 for 61%, 28% and 11% of patients, respectively. The cumulative incidence of 100 and 180 day TRM was 21% and 30%, respectively, with an overall survival (OS) of 15.4 months. Comorbidity, PS, and age greater than 50 predicted increased TRM and decreased OS. In a multivariable model incorporating these predictors (using either CC or KF), age and PS were significant for TRM, while comorbidity and PS were significant for OS. Simple measures of comorbidity, functional status and age predict adverse outcomes after transplantation for hematologic malignancies, even with a reduced intensity regimen. Prospective studies could provide a more accurate estimation of regimen tolerability, particularly in older or sicker patients.

Clinical Predictors for Mortality After Allogeneic Stem Cell Transplantation

Transplant Related Mortality (TRM)Overall Survival (OS)
PredictorIncidence at Day 180Univariate Hazard RatioUnivariate P ValueMultivariate P Value*Univariate Hazard RatioUnivariate P ValueMultivariate P Value*
CC= Charlson Comorbidity Index, KF= Kaplan-Feinstein Scale; *Multivariate analyses include only one comorbidity measure, either KF or CC. Age and PS determined using KF. **Comorbidity scores exclude underlying hematologic malignancies 
Performance Status        
PS=0 0.86       
  4.2 0.002 0.007 2.78 0.003 0.016 
PS>0 0.53       
Comorbidity**        
CC, no comorbidity 0.76       
  2.3 0.042 0.089 2.25 0.014 0.03 
CC, ≥1 comorbidity 0.52       
KF, no comorbidity 0.85       
  2.7 0.027 0.183 2.74 0.004 0.03 
KF, ≥1 comorbidity 0.56       
Age        
Age<50 0.80       
  3.5 0.13 0.47 1.73 0.98 0.34 
Age>50 0.63       
Transplant Related Mortality (TRM)Overall Survival (OS)
PredictorIncidence at Day 180Univariate Hazard RatioUnivariate P ValueMultivariate P Value*Univariate Hazard RatioUnivariate P ValueMultivariate P Value*
CC= Charlson Comorbidity Index, KF= Kaplan-Feinstein Scale; *Multivariate analyses include only one comorbidity measure, either KF or CC. Age and PS determined using KF. **Comorbidity scores exclude underlying hematologic malignancies 
Performance Status        
PS=0 0.86       
  4.2 0.002 0.007 2.78 0.003 0.016 
PS>0 0.53       
Comorbidity**        
CC, no comorbidity 0.76       
  2.3 0.042 0.089 2.25 0.014 0.03 
CC, ≥1 comorbidity 0.52       
KF, no comorbidity 0.85       
  2.7 0.027 0.183 2.74 0.004 0.03 
KF, ≥1 comorbidity 0.56       
Age        
Age<50 0.80       
  3.5 0.13 0.47 1.73 0.98 0.34 
Age>50 0.63       
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Topics:
allogeneic stem cell transplant, radioimmunosorbent test, transplantation, chief complaint, hematologic neoplasms, functional status, toxic effect, alemtuzumab, chemotherapy regimen, disease progression

Author notes

Corresponding author

2005, The American Society of Hematology
2004
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