Wild-type strains of Epstein-Barr virus (EBV) can be distinguished on the basis of variations in the molecular weight of virus-encoded, growth transformationassociated proteins. This approach was used to study the persistence of EBV in two seropositive recipients of allogeneic bone marrow transplants. The first patient received marrow from her EBV-seronegative brother, became EBV seronegative after grafting, and remained so for >1200 days. Subsequently, she became infected with a new EBV strain that differed from her pretransplant strain but was indistinguishable from the virus isolated from her husband. The second patient received marrow from his EBV-seropositive brother. This patient showed only a transient decrease in IgG antibodies to EBV capsid antigen. His pretransplant strain differed from the virus of his donor. On days 252 and 915 after transplantation, lymphoblastoid cell lines were grown from the peripheral blood of the patient and were found to carry exclusively the virus of the donor. These results suggest that the latently EBV-infected host cells reside in a cellular compartment that can be destroyed by graft-versus-host reactivity, irradiation, or cytotoxic drugs. Hemopoietic tissue is the most likely candidate.

Ninety second bone marrow transplants (BMT) for relapsed leukaemia were carried out in 30 European BMT centres. At second BMT, after further treatment in 64 cases, 43 patients were in complete remission or in chronic phase of CML, and 47 were in continuing relapse, accelerated phase or blast crisis of CML. Seventy patients died, 37 from early transplant-related toxicity and relapse or failure to eradicate leukaemia which occurred in 23. There were 20 survivors. The actuarial disease-free survival was 11% with a relapse probability of 69% at 3 years. Associated with reduced graft-versus-host disease (GVHD) prophylaxis during second BMT, the incidence and severity of acute and chronic GVHD, was increased when compared with the first BMT (P = 0.02, and 0.002 respectively for acute and chronic GVHD). In multivariate analysis survival was shown to be favoured by a prolonged interval between first and second BMT (relative risk 1.3/year, P = 0.02), and no or mild chronic GVHD following first BMT (relative risk 2.3, P = 0.02). Continuing remission was favoured by chronic GVHD occurring after second BMT (relative risk 8.1, P = 0.004). These results confirm the high treatment-related mortality following second BMT, but identify superior survival in selected patients. Improved results might be achieved by further reduction in preparative regimen intensity, and increasing graft-versus-leukaemia reactivity.

No abstract

Transplantation of bone marrow can give rise to graft-versus-host disease when donor T lymphocytes, mismatched with the host for major histocompatability (MHC) antigens, become sensitized and attack host tissues. However, graft-versus-host disease can also arise between donor and host with compatible MHC antigens but mismatched for a minor histocompatability antigen. We report here on the occurrence of severe acute graft-versus-host disease in a male patient with acute myeloid leukaemia who had received bone marrow matched for MHC (HLA) antigens from his sister. Strong cytotoxicity of the posttransplantation (that is, donor) lymphocytes against the patient's pretransplantation lymphocytes was found. Thus, the transplanted lymphocytes differed in a non-HLA antigen from the patient. The possible role of this strong cytotoxic minor histocompatability antigen in the development of graft-versus-host disease in man is being evaluated. Furthermore, with the use of cytotoxic T-cell lines, derived from the patient's 6 day effector cells, we are now able to type for it before grafting.

These results suggest that bone marrow transplants currently offer no special advantage over chemotherapy for adults with acute lymphoblastic leukemia in first remission.