Alemtuzumab as a Therapy for Chronic Lung Allograft Dysfunction in Lung Transplant Recipients With Short Telomeres

Front Immunol. 2020 May 28:11:1063. doi: 10.3389/fimmu.2020.01063. eCollection 2020.

Abstract

Alemtuzumab, a monoclonal antibody targeting CD52 that causes lymphocyte apoptosis, is a form of advanced immunosuppression that is currently used as a therapy for refractory acute cellular rejection and chronic lung allograft dysfunction in lung transplant recipients (1-3). Side effects of alemtuzumab include bone marrow suppression, infection, and malignancy. Whether alemtuzumab can be safely used in allograft recipients that have an increased propensity for bone marrow suppression due to telomeropathies is unknown. In a retrospective case series, we report outcomes associated with alemtuzumab in three lung allograft recipients with short telomere lengths, comparing endpoints such as leukopenia, transfusion needs, infection, hospitalization and survival to those of 17 patients without known telomeropathies that received alemtuzumab. We show that the use of alemtuzumab in lung transplant recipients with short telomeres is safe, though is associated with an increased incidence of neutropenia, thrombocytopenia and anemia requiring packed red blood cell transfusions. Alemtuzumab appears to be an acceptable advanced immunosuppressive therapy in patients with telomeropathies, though given the design and scope of this study, the actual clinical effect needs further evaluation in larger trials.

Keywords: alemtuzumab; augmented immunosuppression; chronic lung allograft dysfunction; chronic rejection; lung transplantation; short telomeres; telomere length.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alemtuzumab / adverse effects
  • Alemtuzumab / therapeutic use*
  • Allografts
  • CD52 Antigen / antagonists & inhibitors
  • Female
  • Graft Rejection / genetics
  • Graft Rejection / immunology
  • Graft Rejection / therapy*
  • Hematologic Diseases / etiology
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Lung Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Safety
  • Telomere Shortening* / immunology
  • Treatment Outcome

Substances

  • CD52 Antigen
  • CD52 protein, human
  • Immunosuppressive Agents
  • Alemtuzumab