Practical approach to monitoring and prevention of infectious complications associated with systemic corticosteroids, antimetabolites, cyclosporine, and cyclophosphamide in nonmalignant hematologic diseases

Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):319-327. doi: 10.1182/hematology.2020000116.


Corticosteroids constitute a first-line therapy for adults and children suffering from nonmalignant immune-mediated hematologic diseases. However, high disease relapse rates during the tapering period or upon drug discontinuation result in long-term corticosteroid use that increases the risk of infection. This same concept applies to other immunosuppressive agents, such as antimetabolites, calcineurin inhibitors, and cyclophosphamide. Corticosteroids are associated with a length-of-treatment and dose-dependent risk for infection. Screening and antimicrobial prophylaxis against tuberculosis, hepatitis B, Strongyloides stercoralis, and Pneumocystis jirovecii pneumonia (PJP) might be indicated in patients who are scheduled to be on high-dose corticosteroids for >4 weeks (>30 mg of prednisone-equivalent dose [PEQ]) or in patients chronically treated (≥8 weeks of continuous or intermittent corticosteroid use) with moderate doses (≥15 to <30 mg PEQ). Antimetabolites (azathioprine, mycophenolate) increase the risk of progressive multifocal leukoencephalopathy (PML); however, other opportunistic infections and viral reactivation have also been reported. In case of new onset of neurological symptoms, PML needs to be considered, and an urgent neurology consultation should be obtained. Cyclophosphamide-induced myelosuppression can lead to serious infections related to neutropenia. PJP prophylaxis should be considered with combination therapy of cyclophosphamide and corticosteroids until a PEQ dose ≤ 5 mg/d is reached. Data on infectious risk when cyclosporine is used in patients with nonmalignant hematologic diseases are lacking. Discontinuation of any immunosuppressive agent during an episode of infection is recommended. In all patients, adherence to an age-based immunization schedule is appropriate.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adrenal Cortex Hormones / adverse effects*
  • Adrenal Cortex Hormones / therapeutic use
  • Aged
  • Antimetabolites / adverse effects*
  • Antimetabolites / therapeutic use
  • Cyclophosphamide / adverse effects*
  • Cyclophosphamide / therapeutic use
  • Cyclosporine / adverse effects*
  • Cyclosporine / therapeutic use
  • Female
  • Hematologic Diseases / drug therapy
  • Herpes Zoster / chemically induced
  • Herpes Zoster / prevention & control
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Infection Control
  • Infections / chemically induced*
  • Pneumonia, Pneumocystis / chemically induced
  • Pneumonia, Pneumocystis / prevention & control
  • Strongyloidiasis / chemically induced
  • Strongyloidiasis / prevention & control


  • Adrenal Cortex Hormones
  • Antimetabolites
  • Immunosuppressive Agents
  • Cyclosporine
  • Cyclophosphamide