Problems and strategies for bone marrow transplantation in acute leukemia and chronic myelogenous leukemia.
Certain marrow transplant protocols can now result in a 50-70% long disease-free survival and low relapse rates in acute leukemia (AL) in CR1, CR2, or CML following cytoreduction and HLA-identical marrow infusion. Two-thirds of deaths are due to acute and chronic graft-versus-host disease (GVHD) or viral infection. The other deaths are due to toxicities of the cytoreductive treatment. Prevention of GVHD has been tried by treatment after the transplant or treating the marrow (lymphocyte depletion). Cyclosporine (CsA) or CsA plus methotrexate has reduced acute GVHD but not chronic GVHD. Marrow has been treated with monoclonal antibodies and lectins or elutriated to decrease numbers of T lymphocytes. Some studies have been effective, but the majority have shown an increased number of rejections or leukemic relapses. Apart from teratogenic effects, thalidomide has minimal toxicity. It effectively prevents and treats acute and chronic GVHD in rodent models. Clinical trials will soon begin. Mismatched related or matched unrelated donors have been employed in the clinic with limited success. Alternatively, autologous transplantation in acute leukemia has shown promising results. Possible solutions to remaining problems and strategies will be discussed.
D000208:Acute Disease; D016026:Bone Marrow Transplantation; D003524:Cyclosporins / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008727:Methotrexate / Q000627:therapeutic use; D014181:Transplantation Immunology; D014777:Virus Diseases / Q000150:complications / Q000276:immunology
D003524:Cyclosporins; D008727:Methotrexate