Risk Factors, Prevalence, and Outcomes of Invasive Fungal Disease Post Hematopoietic Cell Transplantation and Cellular Therapies: A Retrospective Monocenter Real-Life Analysis

(1) Background: Autologous, allogeneic hematopoietic cell transplantation (HCT) and other cellular therapies, including CAR T cell and gene therapy, constitute a cornerstone in the management of various benign and malignant hematological disorders. Invasive fungal infections (IFD) remain a significant cause of morbidity and mortality in HCT recipients. Therefore, we investigated the prevalence and risk factors of IFD following HCT and other cellular therapies in an era of novel antifungal prophylaxis. (2) Methods: In this study, we retrospectively enrolled adult HCT recipients who were treated at our JACIE-accredited center according to standard operating procedures over the last decade (2013-2022). (3) Results: 950 patients who received cellular therapies were studied. None of the 19 CAR T cell and neither of the two gene therapy recipients developed IFD whereas 3/456 autologous HCT recipients who suffered from primary refractory/relapsed lymphomas presented with probable IFD. Overall, 11 patients who received allogeneic HCT experienced probable IFD, possible IFD was found in 31/473, and IFD was proven in 10/473. A second IFD episode was present in three patients. Four-year OS was significantly lower in proven compared to probable IFD ( = 0.041) and was independently associated with HCT-CI ( = 0.040) and chronic GVHD ( = 0.045). (4) Conclusions: In this real-world cohort, the prevalence of proven and probable IFD in an era of novel antifungal prophylaxis was found to be relatively low. However, IFDs were associated with poor outcomes for patients who received allogeneic HCT.

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References

Kontoyiannis D, Wessel V, Bodey G, Rolston K . Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis. 2000; 30(6):851-6. DOI: 10.1086/313803. View

Wingard J . Fungal infections after bone marrow transplant. Biol Blood Marrow Transplant. 1999; 5(2):55-68. DOI: 10.1053/bbmt.1999.v5.pm10371357. View

Husain S, Munoz P, Forrest G, Alexander B, Somani J, Brennan K . Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients: clinical characteristics and impact of antifungal agent therapy on outcome. Clin Infect Dis. 2004; 40(1):89-99. DOI: 10.1086/426445. View

Pagano L, Caira M, Nosari A, Van Lint M, Candoni A, Offidani M . Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis. 2007; 45(9):1161-70. DOI: 10.1086/522189. View

Morgan J, Wannemuehler K, Marr K, Hadley S, Kontoyiannis D, Walsh T . Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program. Med Mycol. 2005; 43 Suppl 1:S49-58. DOI: 10.1080/13693780400020113. View

Vora S, Waghmare A, Englund J, Qu P, Gardner R, Hill J . Infectious Complications Following CD19 Chimeric Antigen Receptor T-cell Therapy for Children, Adolescents, and Young Adults. Open Forum Infect Dis. 2020; 7(5):ofaa121. PMC: 7221263. DOI: 10.1093/ofid/ofaa121. View

Chu S, McCormick T, Lazarus H, Leal L, Ghannoum M . Invasive fungal disease and the immunocompromised host including allogeneic hematopoietic cell transplant recipients: Improved understanding and new strategic approach with sargramostim. Clin Immunol. 2021; 228:108731. DOI: 10.1016/j.clim.2021.108731. View

Small T, Papadopoulos E, Boulad F, Black P, Castro-Malaspina H, Childs B . Comparison of immune reconstitution after unrelated and related T-cell-depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions. Blood. 1999; 93(2):467-80. View

Wingard J, Hsu J, Hiemenz J . Hematopoietic stem cell transplantation: an overview of infection risks and epidemiology. Infect Dis Clin North Am. 2010; 24(2):257-72. DOI: 10.1016/j.idc.2010.01.010. View

10.

Lionakis M, Lewis R, Kontoyiannis D . Breakthrough Invasive Mold Infections in the Hematology Patient: Current Concepts and Future Directions. Clin Infect Dis. 2018; 67(10):1621-1630. PMC: 6206100. DOI: 10.1093/cid/ciy473. View

11.

Rodriguez-Lozano F, Onate-Sanchez R, Gonzalvez-Garcia M, Valles-Bergada M, Martinez C, Revilla-Nuin B . Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated Rats. J Clin Med. 2020; 9(6). PMC: 7355877. DOI: 10.3390/jcm9061649. View

12.

Harrison N, Mitterbauer M, Tobudic S, Kalhs P, Rabitsch W, Greinix H . Incidence and characteristics of invasive fungal diseases in allogeneic hematopoietic stem cell transplant recipients: a retrospective cohort study. BMC Infect Dis. 2015; 15:584. PMC: 4696168. DOI: 10.1186/s12879-015-1329-6. View

13.

Marr K, Carter R, Crippa F, Wald A, Corey L . Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002; 34(7):909-17. DOI: 10.1086/339202. View

14.

Park S, Kim K, Jang J, Kim S, Kim W, Chung D . Randomized trial of micafungin versus fluconazole as prophylaxis against invasive fungal infections in hematopoietic stem cell transplant recipients. J Infect. 2016; 73(5):496-505. DOI: 10.1016/j.jinf.2016.06.011. View

15.

Shi J, Pei X, Luo Y, Tan Y, Tie R, He J . Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years. J Zhejiang Univ Sci B. 2015; 16(9):796-804. PMC: 4569688. DOI: 10.1631/jzus.B1500005. View

16.

Little J, Aleissa M, Beluch K, Gonzalez-Bocco I, Marty F, Manne-Goehler J . Low incidence of invasive fungal disease following CD19 chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma. Blood Adv. 2022; 6(16):4821-4830. PMC: 9631654. DOI: 10.1182/bloodadvances.2022007474. View

17.

Wingard J . Infections in allogeneic bone marrow transplant recipients. Semin Oncol. 1993; 20(5 Suppl 6):80-7. View

18.

Sakellari I, Gavriilaki E, Chatziioannou K, Papathanasiou M, Mallouri D, Batsis I . Long-term outcomes of total body irradiation plus cyclophosphamide versus busulfan plus cyclophosphamide as conditioning regimen for acute lymphoblastic leukemia: a comparative study. Ann Hematol. 2018; 97(10):1987-1994. DOI: 10.1007/s00277-018-3383-9. View

19.

Filipovich A, Weisdorf D, Pavletic S, Socie G, Wingard J, Lee S . National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11(12):945-56. DOI: 10.1016/j.bbmt.2005.09.004. View

20.

Gyurkocza B, Rezvani A, Storb R . Allogeneic hematopoietic cell transplantation: the state of the art. Expert Rev Hematol. 2010; 3(3):285-99. PMC: 2943393. DOI: 10.1586/ehm.10.21. View