Neutropenia following immune-depletion, notably CD20 targeting, therapies in multiple sclerosis

Mult Scler Relat Disord. 2024 Feb:82:105400. doi: 10.1016/j.msard.2023.105400. Epub 2023 Dec 22.

Abstract

Neutropenia serves as a risk factor for severe infection and is a consequence of some immune-depleting immunotherapies. This occurs in people with multiple sclerosis following chemotherapy-conditioning in haematopoietic stem cell transplantation and potent B cell targeting agents. Whilst CD52 is expressed by neutrophils and may contribute to early-onset neutropenia following alemtuzumab treatment, deoxycytidine kinase and CD20 antigen required for activity of cladribine tablets, off-label rituximab, ocrelizumab, ofatumumab and ublituximab are not or only weakly expressed by neutrophils. Therefore, alternative explanations are needed for the rare occurrence of early and late-onset neutropenia following such treatments. This probably occurs due to alterations in the balance of granulopoiesis and neutrophil removal. Neutrophils are short-lived, and their removal may be influenced by drug-associated infections, the killing mechanisms of the therapies and amplified by immune dyscrasia due to influences on neutropoiesis following growth factor rerouting for B cell recovery and cytokine deficits following lymphocyte depletion. This highlights the small but evident neutropenia risks following sustained B cell depletion with some treatments.

Keywords: Immune dyscrasia; Immunotherapy; Multiple sclerosis; Neutropenia; Polymorphonuclear neutrophil.

Publication types

  • Review

MeSH terms

  • Alemtuzumab / adverse effects
  • Antigens, CD20
  • Humans
  • Immunologic Factors / adverse effects
  • Multiple Sclerosis* / therapy
  • Neutropenia* / chemically induced
  • Rituximab / adverse effects

Substances

  • Alemtuzumab
  • Rituximab
  • Immunologic Factors
  • Antigens, CD20