Temperature Trajectory Subphenotypes in Oncology Patients with Neutropenia and Suspected Infection.

Abstract

<b>Rationale:</b> Despite etiologic and severity heterogeneity in neutropenic sepsis, management is often uniform. Understanding host response clinical subphenotypes might inform treatment strategies for neutropenic sepsis. <b>Objectives:</b> In this retrospective two-hospital study, we analyzed whether temperature trajectory modeling could identify distinct, clinically relevant subphenotypes among oncology patients with neutropenia and suspected infection. <b>Methods:</b> Among adult oncologic admissions with neutropenia and blood cultures within 24 hours, a previously validated model classified patients' initial 72-hour temperature trajectories into one of four subphenotypes. We analyzed subphenotypes' independent relationships with hospital mortality and bloodstream infection using multivariable models. <b>Measurements and Main Results:</b> Patients (primary cohort <i>n</i> = 1,145, validation cohort <i>n</i> = 6,564) fit into one of four temperature subphenotypes. "Hyperthermic slow resolvers" (pooled <i>n</i> = 1,140 [14.8%], mortality <i>n</i> = 104 [9.1%]) and "hypothermic" encounters (<i>n</i> = 1,612 [20.9%], mortality <i>n</i> = 138 [8.6%]) had higher mortality than "hyperthermic fast resolvers" (<i>n</i> = 1,314 [17.0%], mortality <i>n</i> = 47 [3.6%]) and "normothermic" (<i>n</i> = 3,643 [47.3%], mortality <i>n</i> = 196 [5.4%]) encounters (<i>P</i> < 0.001). Bloodstream infections were more common among hyperthermic slow resolvers (<i>n</i> = 248 [21.8%]) and hyperthermic fast resolvers (<i>n</i> = 240 [18.3%]) than among hypothermic (<i>n</i> = 188 [11.7%]) or normothermic (<i>n</i> = 418 [11.5%]) encounters (<i>P</i> < 0.001). Adjusted for confounders, hyperthermic slow resolvers had increased adjusted odds for mortality (primary cohort odds ratio, 1.91 [<i>P</i> = 0.03]; validation cohort odds ratio, 2.19 [<i>P</i> < 0.001]) and bloodstream infection (primary odds ratio, 1.54 [<i>P</i> = 0.04]; validation cohort odds ratio, 2.15 [<i>P</i> < 0.001]). <b>Conclusions:</b> Temperature trajectory subphenotypes were independently associated with important outcomes among hospitalized patients with neutropenia in two independent cohorts.