Abstract

Charlson Comorbidity Index (CCI) is a weighted index that assigns scores to comorbidities and has been applied to predict mortality for patients (pts) with various medical conditions including solid tumors. Recently, CCI was used to predict the risk of non-relapse mortality (NRM) and overall survival (OS) for pts with hematologic malignancies given ablative or nonablative HCT1. The aim of this study is to a) better define previously identified comorbidities, b) investigate additional HCT-related comorbidities, and c) establish comorbidity scores suitable for HCT. We retrospectively reviewed comorbidities and laboratory data of 1058 pts given HCT at our center between 19972003 after ablative (n=763) or nonablative (n=295) conditioning (Table 1). The following refinements of the original CCI were made: pulmonary functions tests (PFTs) were used for pulmonary, liver function tests for hepatic, and ejection fraction ≤50% added to cardiac comorbidities. Also, new comorbidities were evaluated including bleeding, recent infections under treatment, depression, and obesity. Pts were randomly divided into a training (n=710) and a testing set (n=349). In the training set, the unadjusted HRs for 2-year NRM were calculated for each comorbidity. These values were then adjusted for other comorbidities, disease risk, conditioning type, and pt age. The adjusted HRs were employed as weights for individual comorbidities (Table 2). The refined pulmonary and hepatic comorbidity definitions were useful in identifying pts with increased risk of NRM. In addition, new comorbidities such as infection, bleeding, depression, and obesity appeared to be predictive. Some comorbidities had higher scores than the original CCI due to higher predictive power in the training set. The modified score was then validated in the testing set. The 2-year rates of NRM for scores of 0, 12, and ≥3 were 13%, 24%, and 40%, respectively, and of OS were 71%, 56%, and 37%, respectively. Applying the scores to nonablative and ablative pts, respectively, NRM of 9 vs 12% (p=0.04) were seen for score 0, 17 vs 27% (p=0.002) for scores 12, and 39 vs 42% (p=0.18) for scores ≥3. This modified HCT-specific comorbidity index provided a simple, readily applicable and valid method of estimating the risk of NRM and OS among pts given ablative or nonablative HCT. We suggest using this index in assessing risks for NRM and OS before allogeneic HCT.

Sorror M et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplant comorbidities. Blood. Online April 27, 2004; DOI 10.1182/blood-2004-02-0545

Table 1: pts

Nonablative(n=295), %Ablative(n=763), %P
TBI-total body irradiation, FLU-fludarabine, BU-busulfan, and CY-cyclophosphamide 
Conditioning TBI 23  
 TBI/FLU 77  
 BU/CY 60  
 CY/TBI 40  
Age, median (range) years  54 (1–73) 42 (1–66) <0.0001 
Prior HCT  40 <0.0001 
High disease risk  78 52 <0.0001 
Marrow grafts  38 <0.0001 
Unrelated donor  43 41  
2-year NRM  24 24  
2-year OS  56 61  
Nonablative(n=295), %Ablative(n=763), %P
TBI-total body irradiation, FLU-fludarabine, BU-busulfan, and CY-cyclophosphamide 
Conditioning TBI 23  
 TBI/FLU 77  
 BU/CY 60  
 CY/TBI 40  
Age, median (range) years  54 (1–73) 42 (1–66) <0.0001 
Prior HCT  40 <0.0001 
High disease risk  78 52 <0.0001 
Marrow grafts  38 <0.0001 
Unrelated donor  43 41  
2-year NRM  24 24  
2-year OS  56 61  

Table 2: Modified weighted index

ComorbiditiesAssigned weights
Hypertension 
Arrythmia 
Gastrointestinal 
Mild PFTs reductions 
Mild renal 
Endocrine 
Cardiac 
Asthma 
Mild hepatic 
Diabetes 
Cerebrovascular 
Infection 
Obesity 
Bleeding 
Moderate PFTs reductions 
Peptic ulcer 
Depression 
Valvular 
Moderate-severe renal 
Moderate-severe hepatic 
Prior solid tumor 
Severe PFTs reductions 
ComorbiditiesAssigned weights
Hypertension 
Arrythmia 
Gastrointestinal 
Mild PFTs reductions 
Mild renal 
Endocrine 
Cardiac 
Asthma 
Mild hepatic 
Diabetes 
Cerebrovascular 
Infection 
Obesity 
Bleeding 
Moderate PFTs reductions 
Peptic ulcer 
Depression 
Valvular 
Moderate-severe renal 
Moderate-severe hepatic 
Prior solid tumor 
Severe PFTs reductions 

Author notes

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