Timing Determination of Invasive Fungal Infection Prophylaxis According to Immune Function in HSCT Patients.

Jiexian Ma,Min Wu,Xiaoqin Wang,Yingwei Hu,Yanhui Xie

doi:10.3389/fmicb.2018.00370

Abstract

Patients who receive a hematopoietic stem cell transplantation (HSCT) exhibit an immune defect after recovering from neutropenia. The current guidelines do not recommend fungal prophylaxis in these patients, except for grades III to IV GVHD in HSCT. Thus, the timing for the initiation and cessation of IFI prophylaxis in immune-compromised patients remains a challenging endeavor. We retrospectively analyzed patients who received auto or allo-HSCT and monitored their immune function after recovering from neutropenia by measuring the levels of IgG, IgA, IgM, as well as the number of T, B, NK cells. We found that the level of IgG and NK cell count exhibited a significant difference with the incidence of IFI by logistic regression (p = 0.000 vs. 0.000, respectively) and conditional logistic regression (p = 0.009 vs. p = 0.002). The initiation of IFI prophylaxis was determined to be IgG < 7 mg/mL and NK cell count < 6.5 × 104/mL by an receiver operating characteristic curve separately. Tests in parallel increased the test sensitivity and specificity. Thus, the optimal timing for initiating prophylaxis in patients after HSCT could be IgG < 7 mg/mL or NK cell count < 6.5 × 104/mL. Future large-scale prospective clinical trials are required to verify these findings. Patients who are immuno-compromised after auto or allo-HSCT may benefit from a lower fungi infection incidence with immune surveillance and proper fungal prophylaxis.

Highlights

Invasive fungal infection (IFI) is an important cause of morbidity and mortality among patients with hematological malignancies, in those who receive intensive cytotoxic chemotherapy, immunosuppressive drugs, or hematopoietic stem cell transplantation (HSCT) (Lin et al, 2001; Gavalda et al, 2005; Oliveira-Coelho et al, 2015)
The incidence of IFI post-auto-HSCT was higher than that reported in other clinical trials, the history of prior IFI (9.21%) in these patients was more common than that reported in other clinical trials (Gavalda et al, 2005)
The IFI-attributable mortality rate was higher in HSCT patients than in those receiving chemotherapy alone; the difference was not statistically significant (Neofytos et al, 2009)

Summary

Introduction

Invasive fungal infection (IFI) is an important cause of morbidity and mortality among patients with hematological malignancies, in those who receive intensive cytotoxic chemotherapy, immunosuppressive drugs, or hematopoietic stem cell transplantation (HSCT) (Lin et al, 2001; Gavalda et al, 2005; Oliveira-Coelho et al, 2015). Mucormycosis is the second most common IFI in patients with hematological malignancies (Kontoyiannis et al, 2010; Pagano et al, 2010). The Analyses of The Transplant-Associated Infection Surveillance Network (TRANSNET) database showed that the cumulative annual incidence of IFIs was 7.7, 8.1, 5.8, and 1.7 in every 100 transplants for matched-unrelated allogeneic, mismatch-related allogeneic, matched-related allogeneic, and autologous HSCT patients, respectively (Gavalda et al, 2005). In the TRANSNET database, the estimated postHSCT 1-year survival for invasive candidiasis and invasive aspergillosis is only 33 and 25%, respectively (Kontoyiannis et al, 2010)

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Conclusion