The Impact of Individual Co-Morbidities in Myeloablative Ex Vivo CD34+ Selected Allogeneic Hematopoietic Cell Transplantation
Year: 2020
Type: article
Study design: Observational Study
Abstract: Background Co-morbidities are essential for risk-stratification before allogeneic hematopoietic stem cell transplantation (HCT). We hypothesized that only certain components of the co-morbidity index (HCT-CI) are predictive of outcomes, and that their impact is conditioning-regimen dependent. Methods This retrospective single-center analysis included 580 adult patients who underwent HCT with ex-vivo CD34+ selection following myeloablative conditioning between 2008 and 2018. Results Chemotherapy and total body irradiation (TBI)-based conditioning were given to 75% and 25% of patients, respectively. Common co-morbidities in the population included mild/severe hepatic dysfunction (25%), moderate and severe pulmonary disease (32% and 11%, respectively), prior malignancy (14%), and psychiatric disorders (13%). The median HCT-CI was 2 (IQR 1-3). Among co-morbidities meeting statistical criteria for analysis (prevalence >5% and association with at least 5 outcome events), only severe and moderate pulmonary dysfunction (Figure 1) were associated with decreased overall survival (OS) and increased non-relapse mortality (NRM; HR 1.37, p .023; HR 1.94 p<.001, respectively) in a multivariable Cox model. Using cubic splines, we found that the increase in mortality was mainly attributed to hemoglobin-adjusted DLCO, with an linear increase in mortality risk as DLCO decreases from 80. There was a trend towards poorer OS in the univariate analyses of cardiac disease (p .085) and obesity (p .068). While hepatic dysfunction, defined as either mild or more severe hepatic comorbidity, was not associated with decreased OS in the complete cohort, there was an increased risk in patients conditioned with TBI (HR 2.361, p .004), but not with chemotherapy (HR 0.81, p .234) (Figure 2). Among patients with moderate pulmonary disease, the HR for overall mortality was 1.49 (p .007) in the TBI group and 1.11 (p .170) in the chemotherapy group. Conclusions Our findings suggest that, in CD34+ selected HCT, only certain co-morbidities included in the HCT-CI are likely to contribute to the prognostic assessment of transplantation candidates. Reevaluation of the additive role of co-morbidities in this setting is warranted. In addition, the hazard of co-morbidities may be regimen-dependent, introducing another consideration when selecting the conditioning modality.
Authors: Roni Shouval, Joshua A Fein, Sean M. Devlin, Molly A. Maloy, Nerea Castillo Flores, Richard J. Lin, Ioannis Politikos, Miriam Sanchez, Michael Scordo, Gunjan L. Shah, Juliet N. Barker, Sergio A. Giralt, Boglarka Gyurkocza, Ann A. Jakubowski, Esperanza B. Papadopoulos, Richard J. O'Reilly, Doris M. Ponce, Brian C. Shaffer, Craig S. Sauter, Roni Tamari, Jim Young, Christina Cho, Miguel Perales
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W3002383580