normalities while they are still in a reversible or curable state. References 1. BLOCK JB: Angiosarcoma of the liver fol-
lowing vinyl chloride exposure. JAMA 229: 53, 1974 2. LEE Fl, HARRY DS: Angiosarcoma of the liver in a vinyl-chloride worker. Lancet 1: 1316, 1974 3. MONsON RR, PETERS JM, JOHNSON MN: Proportional mortality among vinyl-chloride workers. Lancet 2: 397, 1974
4. Vinyl chloride, P.V.C., and cancer (editorial). Lancet 1: 1316, 1974
5. FALK H, CItEECH JL, HEATH CW JR. et al: Hepatic disease among workers at a vinyl
chloride polymerization plant. JAMA 230: 59, 1974
6. MAKK L, Citaacsi JL, WHELAN JG JR, et al:
Ibid, p 64
Bone marrow transplantation Although bone marrow transplantation is still an experimental technique, it is generally agreed that this is a realistic form of treatment in cases of immunodeficiency, aplastic anemia and, in all probability, leukemia. Many aspects of the procedure have not yet been standardized because of lack of crucial information, and many more animal experiments and clinical trials are needed. The present status of the technique and its background are discussed in detail in Seminars in Hematology (11: 229, 1974) by workers in a number of countries who are active in this field. There are specific problems to this technique, one *being graft-versus-host (GVH) disease, which differs in different species with respect to such factors as severity and time of onset, and is probably due in all species to incompatibility within immunogenetic systems. The HL-A histocompatibility antigen complex is still considered the major factor governing success or failure of transplantation; HL-A antigens exist on the surface of all nucleated cells and are being constantly renewed. As van Rood of Leyden, the Netherlands, points out in his introduction, there is a great need to devise a protocol enabling successful permanent and complete take of bone marrow grafts without identification of donors and recipients as regards the major histocompatibility complex. There are human chimeras that can live normally and accept each others' skin grafts; what we have to discover is how this is done. It seems reasonable to expect that increasing knowledge of the HL-A system will make the use of unrelated donors feasible, thus greatly increasing the number of bone marrow transplants, now limited to cases in which an HL-A identical sibling donor is available. Another possibility is that better understanding of the HL-A determinants will make it possible in the not-too-distant future to modify them, or the response to them, in such a manner that majorhistocompatibility-complex incompatibility between donor and recipient will not preclude successful transplantation.
This issue of Seminars in Hematology includes a great number of papers on the basic physiology of the HL-A system, as well as a useful summary by van Bekkum on the double barrier in bone marrow transplantation. It is well recognized by now that successful transplantation requires the removal of two immunologic barriers. The first is similar to that encountered in all other organ or tissue grafts, namely the resistance offered by the recipient to the foreign graft. The second barrier is caused by the fact that a bone marrow graft contains or can produce cells that under certain conditions are capable of mounting an immunologic reaction against the recipient - the GVH reaction. This is unique to hematopoietic cell transplants. The GVH barrier is absent in severely immunodeficient patients, such as those with combined immunodeficiency, who therefore provide an ideal opportunity to obtain information about factors governing the severity of the second immunologic obstacle. Van Bekkum discusses two procedures that in theory can be used, which prevent both the acute and the delayed form of GVH reaction in the mouse - removal of immunocompetent cells from the graft and decontamination of the recipient before grafting. In clinical practice a number of technical problems prevent as yet the full application of these solutions. A paper from Baltimore by Santos reviews the problems associated with the use of immunosuppressive agents in bone marrow grafting. However, for the clinician, the most interesting paper in the issue is by Fefer and his colleagues from Seattle, who have the greatest experience in the world of marrow transplantation for aplastic anemia and leukemia. Since 1969 this group has performed approximately 100 marrow transplants in patients with marrow failure or hematologic malignant disease. The results provide grounds for optimism. Of 11 patients with aplastic anemia who have received marrow transplants from identical twins 8 are alive and well years later. Since
270 CMA JOURNAL/FEBRUARY 8, 1975/VOL. 112
the risks of the procedure are negligible, any patient with marrow failure from any cause who has an identical twin should receive a marrow transplant. HL-A-identical transplants in patients with leukemia, however, tend to be associated with greater morbidity and mortality but still benefit a number of patients. In patients with aplastic anemia who do not have an identical donor, conditioning is now carried out with cyclophosphamide before the transplant in order to prevent or modify the anticipated GVH reaction. Of 18 patients so conditioned 10 are alive and well with normal marrow function 4 to 27 months after transplantation. Total body irradiation has not been as successful, so this is no longer a standard procedure. With regard to transplantation of identical twin marrow in cases of leukemia, the authors record four patients who received cyclophosphamide and total body irradiation with or without immunotherapy before transplantation: three had remissions of 3 to 7 months and eight remained in complete remission 3 months to 3 years later. The principal problem has been resistance of the malignant disease to treatment. Results are sufficiently encouraging to suggest that this approach should not be denied to any patient who has an identical twin and does not respond to chemotherapy. Results with allogeneic marrow transplants in leukemia have not been nearly as good as those with allogeneic grafts for aplastic anemia or with twin grafts for leukemia. Nevertheless, 11 of 34 leukemic patients so treated are alive without leukemia 3 to 18 months later. The authors therefore believe that patients with leukemia who are fortunate to have HL-A identical siblings should have a marrow transplant. Hence there is increasing optimism with regard to therapeutic results. Marrow transplantation provides a unique opportunity for furthering knowledge of immunobiology, oncology and other fundamental areas, under conditions of therapeutic benefit to patients. U
lowing vinyl chloride exposure. JAMA 229: 53, 1974 2. LEE Fl, HARRY DS: Angiosarcoma of the liver in a vinyl-chloride worker. Lancet 1: 1316, 1974 3. MONsON RR, PETERS JM, JOHNSON MN: Proportional mortality among vinyl-chloride workers. Lancet 2: 397, 1974
4. Vinyl chloride, P.V.C., and cancer (editorial). Lancet 1: 1316, 1974
5. FALK H, CItEECH JL, HEATH CW JR. et al: Hepatic disease among workers at a vinyl
chloride polymerization plant. JAMA 230: 59, 1974
6. MAKK L, Citaacsi JL, WHELAN JG JR, et al:
Ibid, p 64
Bone marrow transplantation Although bone marrow transplantation is still an experimental technique, it is generally agreed that this is a realistic form of treatment in cases of immunodeficiency, aplastic anemia and, in all probability, leukemia. Many aspects of the procedure have not yet been standardized because of lack of crucial information, and many more animal experiments and clinical trials are needed. The present status of the technique and its background are discussed in detail in Seminars in Hematology (11: 229, 1974) by workers in a number of countries who are active in this field. There are specific problems to this technique, one *being graft-versus-host (GVH) disease, which differs in different species with respect to such factors as severity and time of onset, and is probably due in all species to incompatibility within immunogenetic systems. The HL-A histocompatibility antigen complex is still considered the major factor governing success or failure of transplantation; HL-A antigens exist on the surface of all nucleated cells and are being constantly renewed. As van Rood of Leyden, the Netherlands, points out in his introduction, there is a great need to devise a protocol enabling successful permanent and complete take of bone marrow grafts without identification of donors and recipients as regards the major histocompatibility complex. There are human chimeras that can live normally and accept each others' skin grafts; what we have to discover is how this is done. It seems reasonable to expect that increasing knowledge of the HL-A system will make the use of unrelated donors feasible, thus greatly increasing the number of bone marrow transplants, now limited to cases in which an HL-A identical sibling donor is available. Another possibility is that better understanding of the HL-A determinants will make it possible in the not-too-distant future to modify them, or the response to them, in such a manner that majorhistocompatibility-complex incompatibility between donor and recipient will not preclude successful transplantation.
This issue of Seminars in Hematology includes a great number of papers on the basic physiology of the HL-A system, as well as a useful summary by van Bekkum on the double barrier in bone marrow transplantation. It is well recognized by now that successful transplantation requires the removal of two immunologic barriers. The first is similar to that encountered in all other organ or tissue grafts, namely the resistance offered by the recipient to the foreign graft. The second barrier is caused by the fact that a bone marrow graft contains or can produce cells that under certain conditions are capable of mounting an immunologic reaction against the recipient - the GVH reaction. This is unique to hematopoietic cell transplants. The GVH barrier is absent in severely immunodeficient patients, such as those with combined immunodeficiency, who therefore provide an ideal opportunity to obtain information about factors governing the severity of the second immunologic obstacle. Van Bekkum discusses two procedures that in theory can be used, which prevent both the acute and the delayed form of GVH reaction in the mouse - removal of immunocompetent cells from the graft and decontamination of the recipient before grafting. In clinical practice a number of technical problems prevent as yet the full application of these solutions. A paper from Baltimore by Santos reviews the problems associated with the use of immunosuppressive agents in bone marrow grafting. However, for the clinician, the most interesting paper in the issue is by Fefer and his colleagues from Seattle, who have the greatest experience in the world of marrow transplantation for aplastic anemia and leukemia. Since 1969 this group has performed approximately 100 marrow transplants in patients with marrow failure or hematologic malignant disease. The results provide grounds for optimism. Of 11 patients with aplastic anemia who have received marrow transplants from identical twins 8 are alive and well years later. Since
270 CMA JOURNAL/FEBRUARY 8, 1975/VOL. 112
the risks of the procedure are negligible, any patient with marrow failure from any cause who has an identical twin should receive a marrow transplant. HL-A-identical transplants in patients with leukemia, however, tend to be associated with greater morbidity and mortality but still benefit a number of patients. In patients with aplastic anemia who do not have an identical donor, conditioning is now carried out with cyclophosphamide before the transplant in order to prevent or modify the anticipated GVH reaction. Of 18 patients so conditioned 10 are alive and well with normal marrow function 4 to 27 months after transplantation. Total body irradiation has not been as successful, so this is no longer a standard procedure. With regard to transplantation of identical twin marrow in cases of leukemia, the authors record four patients who received cyclophosphamide and total body irradiation with or without immunotherapy before transplantation: three had remissions of 3 to 7 months and eight remained in complete remission 3 months to 3 years later. The principal problem has been resistance of the malignant disease to treatment. Results are sufficiently encouraging to suggest that this approach should not be denied to any patient who has an identical twin and does not respond to chemotherapy. Results with allogeneic marrow transplants in leukemia have not been nearly as good as those with allogeneic grafts for aplastic anemia or with twin grafts for leukemia. Nevertheless, 11 of 34 leukemic patients so treated are alive without leukemia 3 to 18 months later. The authors therefore believe that patients with leukemia who are fortunate to have HL-A identical siblings should have a marrow transplant. Hence there is increasing optimism with regard to therapeutic results. Marrow transplantation provides a unique opportunity for furthering knowledge of immunobiology, oncology and other fundamental areas, under conditions of therapeutic benefit to patients. U
