Abstract
Transfusion-associated iron overload may lead to increased risk of infection, but its role in myelofibrosis (MF) has been scarcely explored. We evaluated 106 consecutive patients with primary or secondary MF. Up to 38% of patients were transfusion-dependent (TD) with a median of 14 RBC units received. Median observation time was 36 months (range 3–203). Forty-five percent of patients experienced one or more infectious episodes for a total of 69 infectious events, 13 (19%) of which were severe. The 60-month cumulative incidence of infection was 64.1 ± 6.5%. TD patients showed a higher incidence of infection (HR = 2.13, p = 0.019). Transfusion burden was markedly greater in TD patients with infectious complication (median 24 RBC units vs 15 RBC units; p = 0.012). The 60-month overall survival was 40 ± 5.9%. Lower International Prognostic Scoring System (IPSS) risk (p < 0.0001) and ruxolitinib (p = 0.027) were significantly correlated with higher survival. This real-world study showed increased infections in patients with higher transfusion burden. It may therefore be interesting to further investigate the role of iron chelation in improving infection-free survival in MF patients.
This is a preview of subscription content, log in via an institution to check access.
Availability of data and materials
Data and medical charts are available at the “S.C. Ematologia e CTMO, Ospedale Businco, Via Jenner sn, 09124, Cagliari (Italy).
References
Bose P, Verstovsek S. Management of myelofibrosis-related cytopenias. Curr Hematol Malig Rep. 2018;13(3):164–72.
Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91(12):1262–71.
Carreau N, Tremblay D, Savona M, Kremyanskaya M, Mascarenhas J. Ironing out the details of iron overload in myelofibrosis: lessons from myelodysplastic syndromes. Blood Rev. 2016;30(5):349–56.
Toma A, Fenaux P, Dreyfus F, Cordonnier C. Infections in myelodysplastic syndromes. Haematologica. 2012;97(10):1459–70.
Polverelli N, Breccia M, Benevolo G, Martino B, Tieghi A, Latagliata R, et al. Risk factors for infections in myelofibrosis: role of disease status and treatment. A multicenter study of 507 patients. Am J Hematol. 2017;92(1):37–41.
Wang JC, Sindhu H, Chen C, Kundra A, Kafeel MI, Wong C, et al. Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα. PLoS ONE. 2015;10(3):e0116723.
Sant’Antonio E, Bonifacio M, Breccia M, Rumi E. A journey through infectious risk associated with ruxolitinib. Br J Haematol. 2019;187(3):286–95.
Wong CAC, Wong SAY, Leitch HA. Iron overload in lower international prognostic scoring system risk patients with myelodysplastic syndrome receiving red blood cell transfusions: relation to infections and possible benefit of iron chelation therapy. Leuk Res. 2018;67:75–81.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–51.
Jabbour E, Kantarjian HM, Koller C, Taher A. Red blood cell transfusions and iron overload in the treatment of patients with myelodysplastic syndromes. Cancer. 2008;112(5):1089–95.
Angelucci E, Urru SAM, Pilo F, Piperno A. Myelodysplastic syndromes and iron chelation therapy. Mediterr J Hematol Infect Dis. 2017;9(1):e2017021.
Vento S, Cainelli F, Cesario F. Infections and thalassaemia. Lancet Infect Dis. 2006;6(4):226–33.
Pardanani A, Finke C, Abdelrahman RA, Lasho TL, Tefferi A. Associations and prognostic interactions between circulating levels of hepcidin, ferritin and inflammatory cytokines in primary myelofibrosis. Am J Hematol. 2013;88(4):312–6.
Bartoszko J, Panzarella T, Lau A, Schimmer A, Schuh A, Shanavas M, et al. Effect of red blood cell transfusion dependence on the natural history of myeloproliferative neoplasm-associated myelofibrosis. Clin Lymphoma Myeloma Leuk. 2015;15(11):e151–6.
Lussana F, Cattaneo M, Rambaldi A, Squizzato A. Ruxolitinib-associated infections: a systematic review and meta-analysis. Am J Hematol. 2018;93(3):339–47.
Latagliata R, Montagna C, Porrini R, Di Veroli A, Leonetti SC, Niscola P, et al. Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase. Eur J Haematol. 2016;96(6):643–9.
Leitch HA, Chase JM, Goodman TA, Ezzat H, Rollins MD, Wong DHC, et al. Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy. Hematol Oncol. 2010;28(1):40–8.
Acknowledgements
We are deeply grateful to the patients who participated in this study.
Funding
None.
Author information
Authors and Affiliations
Contributions
Conception and design: GC, SG: Collection and assembly of data: GC, MPS, SG, OM, GM, SA, MP, EU, GLN: Statistical analysis: GC, SG, OM: Manuscript writing: GC: Final approval of the manuscript: GC, MPS, SG, OM, GM, SA, MP, EU, GLN.
Corresponding author
Ethics declarations
Conflict of interest
The other authors have no conflicts of interest to disclose.
Ethical approval
Data on patients were retrospectively collected in accordance with the 1975 guidelines of the Declaration of Helsinki.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Caocci, G., Simula, M.P., Ghiani, S. et al. Increased incidence of infection in patients with myelofibrosis and transfusion-associated iron overload in the clinical setting. Int J Hematol 111, 614–618 (2020). https://doi.org/10.1007/s12185-020-02861-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-020-02861-6