The impact of individual comorbidities on non-relapse mortality following allogeneic hematopoietic stem cell transplantation

Abstract

Comorbidity burden is a well-established risk factor for non-relapse mortality (NRM) following allogeneic stem cell transplantation (allo-SCT). We evaluated whether individual comorbidities could better characterize NRM risk. Furthermore, given differing toxicity profiles of conditioning agents, we hypothesized that the hazard of comorbidities is exerted in a regimen-specific manner. This retrospective study included 875 adults treated with an allo-SCT. Six conditioning regimens were considered. Across the entire cohort and within each regimen, the hazard ratio (HR) for NRM associated with individual comorbidities was assessed using multivariable Cox regressions. In the overall population, renal dysfunction, hypoalbuminemia, and severe hepatic disease were associated with the highest risk of NRM (HR 2.1, HR 1.9, HR 1.7, respectively). The risk associated with specific comorbidities was modified by the conditioning regimen and was not correlated with intensity. In patients conditioned with fludarabine/busulfan (Flu/Bu4), NRM risk was increased with cardiac disease (HR 5.54). Severe pulmonary disease and a pre-existing infection were associated with increased NRM risk in patients receiving fludarabine/melphalan (HR 4.9) and fludarabine/treosulfan (HR 3.6), respectively. Comorbidities may exert effects unique to particular conditioning regimens, suggesting that regimen selection should be driven in part by specific comorbidities.

Identifying risk factors associated with worse outcomes in adolescents and young adults undergoing hematopoietic stem cell transplantation

“…[33][34][35] For patients with compromised pulmonary function, therapies with known pulmonary toxicity, such as total body irradiation and busulfan, should likely be dose reduced or avoided as long as alternative strategies can be used to minimize the risk of relapse. 27,36,37 Our study also showed that a history of psychiatric disease was relatively common and associated with worse OS and a higher incidence of TRM in multivariable analysis, while other psychosocial issues were found to be prevalent in AYA patients, but did not correlate with increased mortality. While often overlooked by physicians, 38 prior studies have revealed higher rates of acute GVHD and lower OS in patients with a psychiatric history.…”

“…25,26 The addition of the HCT-CI score to the baseline model did not impact of a high HCT-CI score was also regimen specific. 27 Another recent study in patients with acute myeloid leukemia showed that particular pretransplant comorbidities had a disproportionate effect on outcomes compared to what would have been expected based on the HCT-CI score. 28 These reports support that the presence of certain risk factors may lead to regimen-specific toxicity, and therefore early recognition of these comorbidities may allow providers to tailor conditioning regimens for individual patients in the hopes of improving outcomes.…”

“…Still, our findings suggest that the impact of individual comorbidities is significant and may be lost when combined into a comprehensive risk score such as the HCT‐CI. Similarly, Fein et al demonstrated that certain comorbidities were associated with an increased risk of TRM when particular conditioning regimens were chosen, while the impact of a high HCT‐CI score was also regimen specific . Another recent study in patients with acute myeloid leukemia showed that particular pretransplant comorbidities had a disproportionate effect on outcomes compared to what would have been expected based on the HCT‐CI score .…”

“…The reason why AYAs undergoing allogeneic HSCT have such a substantial rate of reduced pulmonary function is not clear, but is likely related to adverse effects from previous chemotherapeutic agents, irradiation, or infections during prior therapy . For patients with compromised pulmonary function, therapies with known pulmonary toxicity, such as total body irradiation and busulfan, should likely be dose reduced or avoided as long as alternative strategies can be used to minimize the risk of relapse …”

Renal dysfunction within 90 days of FluBu4 predicts early and late mortality

“…ERD was defined as a creatinine clearance <60 ml/min between days 0 and 90 after HSCT. Therefore, this definition, which has been previously described, captures ERD both during inpatient and outpatient encounters and follow-up [16,17]. In patients who had a baseline creatinine clearance under 60 ml/min (n = 3), ERD was defined as a 50% reduction in creatinine clearance from baseline.…”