Bone marrow transplantation.

Abstract

Improvements in the results of bone marrow transplantation for the treatment of SCID may be expected by employing purified stem-cell concentrates for patients who do not have a compatible sibling available. Refinements in the purification technique and its monitoring are required, however. For the same category of patients it seems worthwhile to continue attempts at restoration with liver cells from fetuses less than 12 weeks of age. In addition, full protection against infections should be provided for patients expected to develop GVHD, and, therefore, such patients should only be treated in centers where reverse isolation and bacteriologic decontamination can be performed. In view of the rarity of the disease, transplanters should agree on a limited number of graft protocols. For the treatment of bone marrow aplasia, attempts to identify the factors that can serve to predict the occurrence of GVHD in compatible host-donor sibling pairs should be continued. Only when the patients who will develop GVHD can be recognized in advance will it be feasible to fully exploit available GVHD reductive measures. In particular the role of the intestinal microflora should be investigated in this respect. Experimental evidence is presented, suggesting an aggravating influence of microflora on GVHD lesions, which are primarily induced by histocompatibility reactions. For such studies with incompatible siblings, the dog is the best available animal model. For the selective isolation of hemopoietic stem cells for transplantation purposes (as one means of reducing GVHD), methods for rapid identification of stem cells and immune competent cells, respectively, have to be developed. In leukemia, more research is necessary on the factors that play a role in the late complications of bone marrow transplantation. The toxicity of aggressive regimens employed in the eradication of the leukemia should be further analyzed. The collection of autologous normal hemopoietic stem cells from leukemic patients as introduced by Dicke et al. warrants further exploration to see whether these cells may replace the allogeneic transplantation procedure, thus avoiding all the complications generally encountered in GVHD. For all three diseases, it is extremely important to develop a method for the selection of compatible donors among unrelated individuals, because this will at least double the number of candidates for therapeutic bone marrow transplantation. Current progress in histocompatibility typing in the rhesus monkey and the dog makes these species excellent models for such investigations.