A Modified Hematopoietic Cell Transplantation (HCT)-Specific-Comorbidity Index.
Authors: Sorror Mohamed , Maris Maris , Baron Frederic , Sandmaier Brenda , Maloney David , Storb Rainer , Storer Barry 
Published: April 2020

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 1997–2003 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, 1–2, 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 1–2, 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 0 TBI/FLU 77 0 BU/CY 0 60 CY/TBI 0 40 Age, median (range) years 54 (1–73) 42 (1–66) &lt;0.0001 Prior HCT 40 2 &lt;0.0001 High disease risk 78 52 &lt;0.0001 Marrow grafts 5 38 &lt;0.0001 Unrelated donor 43 41 2-year NRM 24 24 2-year OS 56 61

Table 2: Modified weighted index

Comorbidities Assigned weights Hypertension 0 Arrythmia 0 Gastrointestinal 0 Mild PFTs reductions 0 Mild renal 0 Endocrine 0 Cardiac 1 Asthma 1 Mild hepatic 1 Diabetes 1 Cerebrovascular 1 Infection 1 Obesity 1 Bleeding 1 Moderate PFTs reductions 2 Peptic ulcer 2 Depression 2 Valvular 3 Moderate-severe renal 3 Moderate-severe hepatic 3 Prior solid tumor 3 Severe PFTs reductions 4