Immunohematopoietic stem cell transplantation: Introduction and 35 years of development in South Africa - The historical and scientific perspective
Bone marrow was the traditional graft source when we introduced these procedures to South Africa. Technical details were established using rabbits as the experimental model with translation into a formally structured clinical programme at the University of Cape Town, based in the Groote Schuur Hospital, in 1972. Lack of any infrastructure was overcome by the acquisition of the first continuous-flow cell separator in sub-Sahara to provide for granulocyte transfusions. This was shortly followed by creating a dedicated platelet donor panel and establishing a specialized laboratory for clonogenic assays, flow cytometry, and programmed freezing and by including cryopreservation. Development was constant and seamless but four distinct periods are recognizable. First, guided and constantly encouraged by Professor E Donnall Thomas, was the use of an unfractionated mononuclear population derived from multiple sternal and iliac crest aspirations where complications, as in other centres, included rejection and, particularly troublesome, acute as well as chronic GVHD. The second was centred on CsA in association with Professor Jean Borel at Sandoz in Basle, leading to a decrease in the incidence and severity of the latter immunologic phenomena but not to their abrogation. Third was the opportunity of working with Professor Herman Waldmann and Dr Geoff Hale, first in Cambridge and latterly in Oxford, on immunosuppression achieved by ex vivo T-cell depletion within the broad ambit of the Campath users group. It was here that there was pioneered the alternative new approach of adding the anti-CD 52 MoAb only to the graft in what has become known as the in-the-bag technique. The fourth, securely based on early laboratory and clinical experiences, was a switch to the use of PBSCs mobilized into the circulation with stimulatory peptides. In 1995, this original transplant team relocated to a new academic centre in the private sector and has continued to actively refine the programme over the subsequent decade: the facility at Groote Schuur hospital continues independently. Early recognition that accountability for these expensive and high profile procedures was an important obligation led to consecutive transplants being reported to the International and Autologous registries and now continuing to the Centre for Bone Marrow Transplant Research concurrently with the European Bone Marrow Transplant Registry. This disciplined approach has ensured that all data undergo constant audit and, on such a basis, underpin the unbroken accreditation extending over more than three and a half decades. With difficulties in finding sibling donors, a further achievement was the creation of The South African Bone Marrow Registry and now a proposal to also start a national transplant registry that will complement the survey currently being conducted, on a worldwide basis, by the European Group for Blood and Marrow Transplantation. It is concluded that a properly constituted and functioning multidisciplinary team can cost-effectively carry out immunohematopoietic stem cell grafting even in an under-resourced country with an outcome approximating that reported from recognized First World reference centres. The caveat is that, outside such comprehensive units, results may be less impressive, thereby arguing for resource allocation being directed to academically designated, rather than incentive-driven, preferred providers.