History of Graft-versus-Host Disease

Huib M. Vriesendorp, MD, PhD1,2 and Peter J. Heidt, PhD1,3

1 Phase2Therapy, Den Haag, The Netherlands, hvriesendorp@gmail.com
2 PO Box 2855, Silverthorne, CO, 80498, USA
3 Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands


Nuclear warfare at the end of World War II motivates Dick W. van Bekkum to study Total Body Irradiation (TBI) in animal models. After high dose TBI mice die from ‘primary disease’ or bone marrow aplasia. Intravenous administration of allogeneic bone marrow (BM) cells delays mortality, but does not prevent it. Initially the delayed deaths are said to be due to ‘secondary disease’ which is later renamed Graft-versus-Host Disease (GvHD). GvHD is caused by donor lymphocytes that destroy recipient cells in skin, intestinal mucosa, bile ducts and lymph nodes. GvHD is opposed by Host-versus-Graft Disease (HvGD): host T-lymphocytes destroying the administered allogeneic BM cells, including the administered T lymphocytes of the BM donor.

In 1960 van Bekkum becomes the director of the Radiobiological Institute of the Dutch Organization for Applied Scientific Research TNO in Rijswijk, The Netherlands where he builds a multi-disciplinary team that defines the variables controlling the outcome of a BM transplant.

The team publishes their early results in the Journal of Experimental Hematology [1, 2]. Later, protocols for bone marrow transplantation in patients with Severe Combined Immunodeficiency Disease (SCID), leukemia, lymphoma and other diseases of the hemopoietic system are established.

This review honors the scientific contributions made by Dick van Bekkum and his team in defining the four dominant variables for improving the therapeutic ratio of allogeneic BM transplantation and in fostering the international collaboration necessary to translate this knowledge into current clinical practice.