Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis, the Ottawa Protocol

Curr Protoc. 2022 May;2(5):e437. doi: 10.1002/cpz1.437.

Abstract

Autologous hematopoietic stem cell transplantation (aHSCT) is increasingly used to treat patients with highly active multiple sclerosis (MS) refractory to disease-modifying therapy. Briefly, cyclophosphamide and filgrastim are used to mobilize autologous hematopoietic stem cells (HSC) into the circulation. HSC are harvested by leukapheresis, purified using a CD34 immunomagnetic selection process, and cryopreserved. Busulphan, cyclophosphamide, and rabbit anti-thymocyte globulin are used to destroy the patient's autoreactive immune system, followed by infusion of the previously collected HSC, which reconstitute a naïve and self-tolerant immune system. Many MS patients experience durable remissions with no evidence of new disease activity following aHSCT. Treatment-related toxicity is rare, but potentially life-threatening complications necessitate appropriate patient selection by MS neurologists and HSCT physicians. AHSCT must be performed with a highly trained multidisciplinary team expert to minimize morbidity and mortality. We present the current aHSCT procedure for an MS indication at The Ottawa Hospital, developed from our program's 20-year experience. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Candidate selection Basic Protocol 2: Autologous hematopoietic stem cell mobilization, collection, purification, and cryopreservation Basic Protocol 3: Autologous hematopoietic stem cell transplantation Basic Protocol 4: Supportive care following recovery from aHSCT (Beyond 100 days) Basic Protocol 5: Ongoing evaluation of multiple sclerosis.

Keywords: autologous hematopoietic stem cell transplantation; immune reconstitution; immunotolerance; multiple sclerosis; patient selection.

MeSH terms

  • Cyclophosphamide / therapeutic use
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Multiple Sclerosis* / therapy
  • Transplantation, Autologous / methods

Substances

  • Cyclophosphamide