The Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) Can Prospectively Discriminate Risks Affecting Overall Survival in Pediatric and Adult Patients with Non-Malignant Diseases
Authors: Thakar Monica S , Logan Brent R. , Pasquini Marcelo C. , McCarthy Philip L. , Ho Vincent T , Cooke Kenneth R. , Zhu Xiaochun , Rizzo J. Douglas , Sorror Mohamed L. 
Published: October 2019

Abstract
Abstract 737
The HCT-CI was developed to summate the effect of 17 weighted comorbidities on non-relapse mortality and overall survival (OS) in the allogeneic HCT setting. However, only 3% of patients included in the initial HCT-CI study had non-malignant diseases (Sorror M. et al, Blood 2005). In an attempt to broaden the application of HCT-CI by assessing its prognostic effect on overall mortality in patients with nonmalignant diseases, we conducted a prospective observational study collecting comorbidities on all patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from December 2007 to December 2009. A total of 853 patients with non-malignant diseases were identified, including severe aplastic anemia (SAA, n=404); inherited disorders of erythrocytes (n=180), histiocytes (n=68), metabolism (n=41), and platelets (n=6); primary immune deficiencies (n=149); and autoimmune diseases (n=5). Patients were transplanted at a median of 12 (<1–70) years of age (72% of patients were less than 20 years of age at HCT), and a median of 10 (<1–500) months from diagnosis. Donors were unrelated (n=414), HLA-matched siblings (n=356), other relatives (n=76), or syngeneic (n=7). Transplant regimens were predominantly fludarabine (Flu) and total body irradiation (n=144); Flu and melphalan (n=140); busulfan and cyclophosphamide (CY, n=138); CY and antithymocyte globulin (n=137) for conditioning, and methotrexate with cyclopsporine (n=279) or tacrolimus (n=160) for post-grafting immunosuppression, respectively. Karnofsky/Lansky scores were ≥90% in 77% of patients. HCT-CI scores were 0 (64%), 1 (13%), 2 (6%), 3 (8%), 4 (5%), and ≥5 (4%). The top three HCT-CI comorbidities reported were active infection (8%) and pulmonary disease (severe 8% and moderate 7%). With a median follow-up of 27 (1–51) months, the OS for HCT-CI 0 (n=546), 1–2 (n=161), and ≥3 (n=144) at 3 years was 85%, 81%, and 63%, respectively (figure, p<0.001). Multivariate analyses were adjusted for age, conditioning regimen, donor type and HLA-match status. In these analyses, higher HCT-CI scores were associated with increased overall mortality as judged by increasing hazard ratios (HR, p<0.001) compared to patients with HCT-CI of 0. This was mostly a result from the effect of HCT-CI scores of ≥3 (HR 2.54, 95% Confidence Interval [CI] 1.68–3.83; p<0.0001) than from HCT-CI scores of 1–2 (HR 1.15; 95% CI 0.72–1.82 p=0.56). The negative effect of HCT-CI scores ≥ 3 on OS was preserved in subgroup analyses of pediatric (<20 years old; HR 2.43, 95% CI 1.30–4.54, p<0.005) and adult patients (≥20 years old; HR 2.91, 95% CI 1.56–5.41, p<0.001), and in SAA (HR 2.91, 95% CI 1.56–5.41, p<0.001). In conclusion, in a relatively large sample size, this study demonstrates that HCT-CI can also be used to predict OS in patients with non-malignant diseases. In particular, patients with HCT-CI scores of ≥3 experienced higher overall mortality independent of age group, conditioning regimen, donor type and HLA matching. HCT-CI is an important instrument to assist in patient counseling and transplant associated risk assessment in patients with nonmalignant diseases.

Disclosures:
Pasquini: Miltenyi Biotec: Consultancy, Honoraria.