How we approach: Severe congenital neutropenia and myelofibrosis due to mutations in VPS45

Pediatr Blood Cancer. 2019 Jan;66(1):e27473. doi: 10.1002/pbc.27473. Epub 2018 Oct 7.

Abstract

Mutations in the VPS45 gene lead to a severe primary immune deficiency characterized by severe congenital neutropenia and primary myelofibrosis, leading to overwhelming infection and early death. This condition is exceedingly rare with only 16 patients previously reported, including four with successful hematopoietic stem cell transplantation. We review the pathophysiology underlying this condition and detail our approach to treatment, particularly vis-à-vis bone marrow transplantation and the challenges of transplanting into a diseased bone marrow niche. We provide an update on the progress of our three previously reported patients, and two additional patients transplanted at our center.

Keywords: bone marrow transplantation; infection; myelofibrosis; severe combined neutropenia.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Combined Modality Therapy
  • Congenital Bone Marrow Failure Syndromes
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Infant
  • Male
  • Mutation*
  • Neutropenia / congenital*
  • Neutropenia / genetics
  • Neutropenia / pathology
  • Neutropenia / therapy
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / pathology*
  • Primary Myelofibrosis / therapy
  • Prognosis
  • Transplantation Conditioning
  • Vesicular Transport Proteins / genetics*
  • Young Adult

Substances

  • VPS45 protein, human
  • Vesicular Transport Proteins

Supplementary concepts

  • Neutropenia, Severe Congenital, Autosomal Recessive 3