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Infectious medicine, virology

Frequency of infections in 948 MPN patients: a prospective multicenter patient-reported pilot study

Leukemia volume 34, pages 1949–1953 (2020)Cite this article

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A Correction to this article was published on 10 July 2020

This article has been updated

Recently, several studies have reported on immunosuppression and infectious complications in patients with myeloproliferative neoplasms (MPN) receiving Janus kinase (JAK) inhibitor therapy (reviewed in [1]). These datasets included analyses of large multicenter trials comparing JAK inhibitor therapy with best available therapy or placebo control. Specific infections such as herpes virus reactivation appear to be more prevalent in patients treated with the JAK inhibitor ruxolitinib (RUX) and opportunistic infections have been described also outside of clinical trials [1]. However, it is not known to which extent the underlying malignancy (MPN) contributes to immunosuppression and susceptibility to infection. Studies from a registry provided early evidence that the risk of MPN patients to die from infections may be increased when compared with normal population controls [2] and this finding was most recently underpinned by a large dataset of 8363 MPN patients [3]. MPN patients were at higher risk for severe bacterial and viral infections judged by hospital admissions and deaths from infection. The question how the type of pharmacologic treatment, the MPN subtype or the disease stage may influence the risk for infectious complications remains still unclear. Immunosuppressive effects of JAK inhibitors are determined by their specificity [4], while other cytoreductive agents such as hydroxycarbamide or interferons may also compromise the function of immune cells. Finally, molecular and clinical heterogeneity of MPN, its impact on cellular signaling, immune function and the inflammatory phenotype may vary depending on the type of driver mutation and disease burden [5, 6].

This international, patient-reported, multicenter pilot study aimed to assess for the overall incidence of infections as well as prophylactic and therapeutic measures in MPN patients in an unbiased manner. The trial included seven academic centers and two private hematology practices in two countries (Germany and Italy) and recruited between October 2018 and March 2020. The study was terminated at the onset of the CoVID-19 pandemic in Europe to avoid potential bias. Patients diagnosed with any subtype of MPN and with or without cytoreductive or symptomatic therapy were evaluated. Due to the challenge of under-reporting observed in registries or chart reviews conducted by MPN specialists [7], this pilot study was conducted as a paper–pencil based questionnaire that was completed by the patient and finally approved by the responsible physician. While this approach does not account for infections in age-matched healthy controls, duration of disease, or treatment prior to the observation period, it avoids bias for severe infections or hospitalization and includes infectious complications treated in an outpatient setting. Descriptive analysis was used to assess differences regarding the subtype of MPN, driver mutations, therapy, type, frequency and severity of infections, prophylaxis and treatment as well as assessment of chronic infections and vaccination status. For statistical comparisons, bivariate analysis by Spearman Rank Test was used when normal distribution was not given. All patients reported on the time span of 12 months prior to answering the questionnaire and independent of duration or subtype of disease.

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Acknowledgments

Open access funding provided by Projekt DEAL.

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Author notes

  1. These authors contributed equally: Carl C. Crodel, Kathleen Jentsch-Ullrich

  2. These authors jointly supervised this work: Francesca Palandri, Florian H. Heidel

Authors and Affiliations

  1. Innere Medizin 2, Hämatologie und Onkologie, Universitätsklinikum Jena, Jena, Germany

    Carl C. Crodel, Verena Hofmann, Tobias Rachow, Philipp Ernst, Annamaria Brioli, Marie von Lilienfeld-Toal, Andreas Hochhaus & Florian H. Heidel

  2. Gemeinschaftspraxis Hämatologie und Onkologie, Magdeburg, Germany

    Kathleen Jentsch-Ullrich

  3. Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany

    Steffen Koschmieder & Susanne Isfort

  4. Germany Study Group MPN, GSG-MPN, Germany

    Steffen Koschmieder, Martin Griesshammer, Konstanze Döhner, Philipp J. Jost, Susanne Isfort, Frank Stegelmann & Florian H. Heidel

  5. Praxis Hämatologie und Onkologie, Lüneburg, Germany

    Dietrich Kämpfe

  6. OSHO Study Group—Working Party MPN, WP-CMPN, Germany

    Dietrich Kämpfe & Florian H. Heidel

  7. Johannes Wesling Klinikum, Universitätsklinikum für Onkologie, Hämostaseologie und Palliativmedizin, UKRUB, Universität Bochum, Minden, Germany

    Martin Griesshammer

  8. Innere Medizin III, Universitätsklinikum Ulm, Ulm, Germany

    Konstanze Döhner & Frank Stegelmann

  9. Medizinische Klinik 3, Hämatologie, Onkologie, Klinikum rechts der Isar, Technische Universität München, München, Germany

    Philipp J. Jost & Stefanie Jilg

  10. Klinik für Hämatologie und Onkologie, Universitätsklinikum Magdeburg, Magdeburg, Germany

    Denise Wolleschak

  11. Praxis für Hämatologie und Onkologie, Erding, Germany

    Stefanie Jilg

  12. Institute of Hematology and Clinical Oncology “L. and A. Seràgnoli” Sant’Orsola-Malpighi University Hospital, Bologna, Italy

    Guiseppe Auteri & Francesca Palandri

Authors
  1. Carl C. Crodel
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  2. Kathleen Jentsch-Ullrich
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  20. Florian H. Heidel
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Contributions

CCC, FP, AH, MvLT, and FHH developed the study protocol and questionnaire. CCC and VH analyzed the data. FP, KJU, DK, MG, SK, KD, PJJ, DW, SI, FS, TR, GA, SJ, PE, and FHH collected and analyzed the data. FHH wrote the manuscript.

Corresponding author

Correspondence to Florian H. Heidel.

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Conflict of interest

FHH: research funding: Novartis, Celgene, CTI; consultant for Novartis, Celgene, AOP and CTI. AH: research support: Novartis, BMS, Pfizer, Incyte. PJJ: advisory role, received honoraria, research funding, and/or travel/accommodation expenses from: Abbvie, Incyte, Bayer, Boehringer, Novartis, Pfizer, Servier, BMS and Celgene. MvLT: research funding: Celgene, Novartis, Gilead; honoraria and consultancy: Celgene, Janssen, Medac, Gilead, BMS, Oncopeptides, Takeda.

Ethical standards

The questionnaire and study protocol were approved by the Ethics Committee of the Jena University Hospital (Protocol #2018-1198-Reg).

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Crodel, C.C., Jentsch-Ullrich, K., Koschmieder, S. et al. Frequency of infections in 948 MPN patients: a prospective multicenter patient-reported pilot study. Leukemia 34, 1949–1953 (2020). https://doi.org/10.1038/s41375-020-0890-1

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