Evaluating the Prognostic Value of Procalcitonin in Infections Among Patients with Hematologic Malignancies

Introduction: Infections are the main cause of non-disease related mortality in patients with hematological neoplasms, with an incidence of 30% and a mortality rate of 11%. Procalcitonin (PCT) has demonstrated significant prognostic value in different infections. In the context of patients with hematological neoplasms, there are currently no clear recommendations for its use. Furthermore, in this population, fungal and viral infections are common, and the role of PCT in identifying and managing these infections is not well-defined. Therefore, the objective of this study was to analyze the prognostic impact of PCT in these patients.

Methods: It is a retrospective cohort of patients with hematological neoplasms and infections requiring hospitalization between 2019 and 2023 at a private referral center in Mexico City. Risk factors for septic shock and in-hospital mortality were determined in a univariate and multivariate analysis. PCT was measured at admission and 48 hours after.

Results: A total of 238 patients were included with a median age of 61 years (range 18-88); 48.7% were women. The diagnoses included acute myeloid leukemia in 38.7%, acute lymphoblastic leukemia in 23.1%, non-Hodgkin lymphoma in 18.5%, multiple myeloma in 15.5%, and Hodgkin lymphoma in 3.4%. The median PCT at admission was 0.2 ng/mL (IQR 0.08-0.58), and at 48 hours 0.47 ng/mL (IQR 0.15-1.99), with a 48-hour PCT / initial PCT ratio of 1.33 ng/mL (IQR 1.00-2.95).

Admission PCT >0.46 ng/ml was associated with a higher probability of having a microbiological isolation with a sensitivity of 91% and a specificity of 40%, with a positive predictive value of 48% and a negative predictive value of 88%.

The rate of septic shock was 29.0%, and in-hospital mortality 15.1%.

In the univariate analysis, the risk factors for the development of septic shock were: pneumonia (OR 2.12 [95% CI: 1.18-3.81], p=0.014), invasive fungal Infection (IFI) (OR 5.20 [95% CI: 2.24-12.06], p<0.001), admission PCT ≥0.4 ng/mL (OR 11.03 [95% CI: 5.76-21.12], p<0.001) and an ECOG performance status (PS) ≥3 (OR 5.73 [95% CI: 2.89-11.37], p<0.001). In the multivariate analysis the significant factors were pneumonia (OR 2.19 [95% CI: 1.02-4.73], p=0.046), admission PCT >0.4 ng/mL (OR 10.41 [95% CI: 5.11-21.22], p<0.001), ECOG PS ≥3 (OR 4.06 [95% CI: 1.78-9.28], p=0.001). The rate of septic shock in the patients with pneumonia, admission PCT ≥0.4 ng/ml and an ECOG PS ≥ 3 was 100% vs. 24.7%, p<0.001.

In the univariate analysis, the risk factors for in-patient mortality were IFI (OR 7.59 [3.18-18.12], p<0.001), admission PCT ≥0.4 ng/ml (OR 4.2 [95% CI: 2.02-8.79], p<0.001), 48-hour PCT ≥0.85 (OR 11.03 [95% CI: 4.37-27.84], p<0.001), ECOG PS ≥3 (OR 11.66 [95% CI: 5.27-25.79], p< 0.001), pneumonia (OR 3.84 [95% CI: 1.85-7.98], p<0.001), high-dose steroids (OR 2.25 [95% CI: 1.09-4.66], p=0.03). In the multivariate analysis for in-patient mortality the risk factors were: 48 hours-PCT ≥0.85 (OR 6.87 [95% CI: 1.97-23.93], p=0.002), ECOG PS ≥3 (OR 8.20 [95% CI: 3.17-21.24], p<0.001) and pneumonia (OR 2.70 [95% CI: 1.05-6.96], p = 0.039).

When comparing patients with and without severe neutropenia, the rate of septic shock (31% vs. 25%, p=0.313) and mortality (14% vs. 15%, p=1) were not different.

When including only patients with severe neutropenia, in the multivariate analysis for septic shock, the independent risk factors were: admission PCT ≥0.4 ng/ml (OR 7.69 [95% CI: 3.15-18.79], p<0.001), an ECOG PS ≥3 (OR 4.07 [95% CI: 1.47-11.30], p=0.007) and an IFI (OR 7.84 [1.66-36.99], p=0.009). The risk factors for in-patient mortality in the multivariate analysis were: 48-hour PCT ≥0.85 ng/ml (OR 6.62 [95% CI: 1.05-41.54], p=0.044) and an ECOG PS ≥3 (OR 13.26 [95% CI: 3.45-50.9], p<0.001).

The in-hospital mortality for the patients with a 48-hour PCT ≥0.85 ng/ml and an ECOG PS ≥3 was 65% vs. 8.1% for the patients with one or none of these factors, p<0.001.

Conclusion: PCT levels are independent risk factor for the development of septic shock and in-hospital mortality in patients with hematological neoplasms and severe infections. It is a useful prognostic marker for both patients with and without severe neutropenia. Since infections are the main cause of non-disease related mortality during treatment, the incorporation of PCT levels in the treatment algorithms for infections in patients with hematologic malignancies can potentially improve the outcomes and should be evaluated prospectively.

Neme Yunes:BMS: Honoraria, Speakers Bureau; Novartis: Honoraria; Janssen: Honoraria. Demichelis:TEVA: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; AMGEN: Honoraria; Abbvie: Consultancy, Honoraria. Ontiveros-Austria:Servier: Speakers Bureau. Inclan-Alarcon:Abbvie: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; johnson & johnson: Consultancy, Speakers Bureau; Beigene: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau.