Safely achieving tolerance to stem cell transplantation

Dale Greiner and colleagues at the University of Massachusetts have developed a protocol for achieving stem cell transplantation that is not limited by significant patient side-effects and may not necessarily require that donor blood, bone marrow or whole organs are a “match” with the recipient –- characteristics that make these new procedures highly attractive for development and use in clinical human transplantation.

Hematopoietic stem cells (HSCs) are parent cells in the bone marrow that give rise to blood cells. Allogeneic stem cell transplantation has great potential in the treatment of malignancy, genetic disorders, and in solid organ transplantation. However, the radiation or high doses of chemotherapy commonly used in the treatment of blood cancers to destroy abnormal HSCs–a process called myeloablation– is very toxic.

Furthermore, even following this form of conditioning, many patients develop graft-versus-host disease (GVHD), where the host immune system launches an attack against the newly transplanted HSCs.

In order to avoid both lethal conditioning and GVHD, new HSC transplant strategies are in development. Greiner et al. have adapted a costimulatory blockade–based protocol developed for solid organ transplantation for use in stem cell transplantation. The authors combined donor-specific transfusion and anti-CD154 monoclonal antibody administration to achieve functional donor and recipient HSC populations within the donor without the need for myeloablation or stimulating the induction of GVHD.

TITLE: Hematopoietic chimerism and central tolerance created by peripheral-tolerance induction without myeloablative conditioning

AUTHOR CONTACT:
Dale L. Greiner
University of Massachusetts Medical School, Worcester, Massachusetts, USA
Phone: 508-856-3800
Fax: 508-856-4093 E-mail: dale.greiner@umassmed.edu