Summary:Among 551 consecutive recipients of allogeneic bone marrow transplants, 451 survived more than 3 months and were evaluated for chronic graft-versus-host disease (GVHD). Most of the donors were HLA-identical siblings or parents (n = 334). Patients with HLA-mismatched donors (n = 30) and matched unrelated donors (MUD) (n = 87) were also included in the study. In the analysis of all patients, the 5-year cumulative incidence of chronic GVHD was 45%. We analysed 34 risk factors. High recipient age was the single most important risk factor (P Ͻ 0.001). Other significant risk factors in multivariate analysis were: acute GVHD grades I-IV (P Ͻ 0.001), immune female donor to male recipient (P = 0.006) and chronic myelogenous leukaemia (CML), compared with all other diagnoses (P = 0.014). The cumulative 5-year incidence of chronic GVHD, with no significant risk factors present, was 9%, 29% with one risk factor, 53% with two, 68% with three and 75% with all four risk factors present. In patients with HLAidentical sibling donors and GVHD prophylaxis consisting of a combination of methotrexate (MTX) and cyclosporin A (CsA) (n = 208), increasing recipient age (P Ͻ 0.001) and CML (P = 0.007), were found to be significant risk factors for chronic GVHD. Finally, a multivariate analysis in recipients of bone marrow from unrelated donors (n = 89) showed recipient age alone (P = 0.006) to be significantly associated with chronic GVHD.

Preemptive therapy based on polymerase chain reaction for CMV DNA was associated with reduced risks for CMV disease, CMV-associated death, and TRM, whereas other prophylactic modalities did not give additional benefit.

Long-term immunity to measles, mumps, and rubella viruses was studied in 57 patients after allogeneic bone marrow transplantation. Among patients who were seropositive at the time of transplant, 51% had retained antibodies to measles, 42% had retained antibodies to mumps, and 76% had retained antibodies to rubella 2 y later. There was no difference in the ability to retain antibodies to these viruses between patients with and those without chronic graft-versus-host disease (GVHD). Twenty seronegative patients without active chronic GVHD or ongoing immunosuppressive treatment were vaccinated with a live attenuated trivalent vaccine against measles, mumps, and rubella. No early or late side effects were detected after the vaccinations. The percentages of patients who seroconverted after vaccination were 77%, 64%, and 75% for measles, mumps, and rubella, respectively. Vaccination of transplant recipients with a live attenuated vaccine against measles, mumps, and rubella is safe and usually effective 2 y after transplant if the patients do not have active chronic GVHD or ongoing immunosuppressive treatment at the time of vaccination.

An ELISA was used to study long-term immunity and immunization responses to tetanus toxoid in 48 bone marrow transplant recipients. Among patients who were seropositive to tetanus before transplant, 51% had lost their seropositivity 1 year later. All patients who were not reimmunized with tetanus toxoid were seronegative 2 years after transplant. All patients who were seronegative before transplant remained seronegative 1 year later regardless of the donor's serologic status. There was no difference in the ability to remain seropositive to tetanus toxoid between patients with and without chronic graft-versus-host disease. Of 21 patients immunized with one dose of tetanus toxoid 1 year after transplant, 14 were seronegative at the time of immunization (response rate, 64%). At 1 year after immunization, 7 remained seropositive. Ten patients were reimmunized with two doses of tetanus toxoid. All responded and 90% remained seropositive 1 year later. When 21 patients were primarily immunized with three doses of tetanus toxoid, all patients seronegative at immunization responded and all tested patients remained seropositive 2 years later. The immunization responses were significantly superior in patients receiving three doses compared with those who received one. Reimmunization with tetanus toxoid of long-term survivors after marrow transplant seems necessary. A three-dose immunization schedule is recommended to obtain an adequate immune response.