Impact of Comorbidities on Early and Late Mortalities After Allogeneic Hematopoietic Cell Transplantation (HCT)
Authors: Sorror Mohamed L. , Storb Rainer , Sandmaier Brenda M. , Bhatia Smita , Maziarz Richard T. , Pulsipher Michael A. , Maris Michael T. , Deeg H. Joachim , Appelbaum Frederick R. , Maloney David G. , Martin Paul J , Storer Barry 
Published: October 2019

Abstract
Abstract 326
The HCT-specific-comorbidity index (CI) is a tool used to assign scores to comorbidities that affect outcomes after HCT. The index has been shown to be an important pre-transplant predictor of non-relapse mortality (NRM) and overall survival (OS) after HCT. Whether the HCT-CI could provide predictive information at later time points after HCT or could be used to optimize exclusion criteria is unknown. Here, we investigated 1) survival rates, as stratified by pre-transplant HCT-CI scores, among survivors at different landmark time points after HCT and 2) HCT-CI scores associated with the highest mortality rates. To answer these questions, we analyzed data from 3033 consecutive patients (pts) treated with allogeneic HCT between 2000 and 2006 from HLA-matched related (55%) or unrelated (45%) donors at 5 collaborating institutions. Median age was 45 (range 0.1–74.5) years. HCT-CI scores of 0, 1–2, 3, and ≥4 were assigned to 32%, 31%, 18%, and 19% of pts, respectively. Diagnoses were myeloid (59%) and lymphoid (35%) malignancies in addition to other non-malignant diseases (4%) and other malignancies (2%). Among pts with myeloid and lymphoid malignancies, 38% were considered to have low-risk disease (malignancy in remission, refractory anemia without excess blasts, or chronic myeloid leukemia in chronic phase) and the remainder high-risk. Conditioning regimens were classified as high-dose (62%), reduced-intensity (15%), or nonmyeloablative (23%). Stem cell source was marrow (20%) or G-CSF-mobilized blood cells (80%). Three-year Kaplan-Meier estimates of subsequent overall survival were calculated from day 0, day 100, 1 year, 3 years, and 5 years after HCT. The HCT-CI stratified survival rates from day 0, and the significant association of the pre-transplant HCT-CI with survival persisted at all subsequent landmarks (Table 1). Among 5-year survivors, the subsequent 3-year survival rates were 94%, 91%, 88%, and 81% for pts with HCT-CI scores of 0, 1–2, 3, and ≥4, respectively. By comparison, expected mortality rates, based on sex-specific 2001 US life table data from the National Center for Health Statistics, for an age- and gender-matched general population would be 98% at 3 years.Table 1:3-year survival rates after various landmark times following allogeneic HCT as stratified by HCT-CI scoresHCT-CI scoresSurvival rates, %day 0day 1001 year3 years5 years072768592941–2566378879134048708688≥42737547681p<0.0001<0.0001<0.0001<0.00010.009
Among 1001 5-year survivors after HCT, 72 pts died within the subsequent 3-years. Charts of those 72 pts were evaluated for causes of death. Deceased pts with HCT-CI scores of 0 (n=21) and ≥1 (n=51) were compared for the frequency of causes of death. Five categories of death causes could be identified with the following ratios of frequency among pts with HCT-CI scores of 0 versus ≥1: relapse or complications from relapse treatment (1:1), second malignancy and complications from its treatment (1:3), graft-versus-host disease (GVHD) or its complication (1:1), infections (1:1), and acute or chronic organ failure (1:5), respectively.
Subsequent analyses focused on pts with the highest HCT-CI scores. Pts with HCT-CI scores of 6 (n=103), 7 (n=32) or, ≥8 (n=24) had overall mortality rates of 55%, 47%, and 88% at 1 year and 70%, 66%, and 88% at 2 years, respectively. Among pts with HCT-CI scores of ≥6, those with low-risk myeloid, high-risk myeloid, and lymphoid malignancies had 2-years mortality rates of 68%, 77%, and 66%, respectively (Table 2).Table 2:Mortality rates among pts with HCT-CI scores of ≥6 as stratified by disease categoryMortality rates atLow-risk myeloidHigh-risk myeloid %Lymphoid6-months2855341-year4863492-years687766
Impact of comorbidities on HCT mortality persists among late survivors. Comorbidities present at the time of HCT appear to be associated with an increased risk of late-onset organ failure and with development or mortality from second malignancies. The HCT-CI scores calculated at time of HCT provides important predictive information at different intervals after HCT.
Increasing HCT-CI scores were associated with increasing mortality rates, but a level at which the HCT-CI score predicted a complete lack of benefit from the HCT was not identified regardless of the diagnosis category. Prospective observational studies that compare outcomes between HCT and conventional treatment among pts with high HCT-CI scores are in progress.

Disclosures:
No relevant conflicts of interest to declare.