Principles of alemtuzumab immunoablation in hematopoietic cell transplantation for non-malignant diseases in children: A review

Pediatr Transplant. 2018 Mar;22(2). doi: 10.1111/petr.13142. Epub 2018 Jan 19.

Abstract

Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable. In addition, the degree of immune suppression achieved with alemtuzumab has allowed for a reduction in the intensity of myeloablative cytotoxic agents included in some HCT conditioning regimens, allowing for fewer acute and late toxicities. This review paper will provide a comprehensive summary of the mechanism of action, PKs, dosing, and timing of alemtuzumab, a brief description of its use in various allogeneic HCT protocols for non-malignant conditions and a summary of the data regarding its use for GVHD therapy. The goal of this review was to provide an understanding as to how alemtuzumab might be safely incorporated into HCT conditioning regimens for children with non-malignant disease, allowing for expanded access to curative HCT therapy.

Keywords: immunosuppression; non-myeloablative hematopoietic cell transplantation; pediatric.

Publication types

  • Review

MeSH terms

  • Alemtuzumab / pharmacokinetics
  • Alemtuzumab / therapeutic use*
  • Child
  • Drug Administration Schedule
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use*
  • Transplantation Conditioning / methods*

Substances

  • Immunosuppressive Agents
  • Alemtuzumab