Since 1993, the National Cord Blood Program has provided cord blood transplants to 1750 recipients worldwide, of whom 396 ≥16 years old (22.6%). Of the adults, 65% were ≥25 years old, 90% had hematologic malignancies, 33% had advanced disease (IBMTR classification), 13% had received a prior auto or allograft and 11% received double-unit transplants. Of single-unit transplant recipients, 22% had 1, 66% had 2 and 10% had 3 HLA mismatches (HLA-A and -B at serological resolution level, DRB1 at the allele level). TNC doses were below 5 × 107 in all but 5 patients. Engraftment was associated with TNC dose (P = 0.004) and HLA-matching (p = 0.003), especially when recipients of mismatched only in the GvH direction were counted as matched (p = 0.001). Significant differences in the probability of engraftment were also related to the conditioning regimens and to the use of double unit transplantation. Acute GvHD grade III–IV developed in 25% of cases, and was lower (≈10%) in cases without HLA mismatches in the GvHD direction. This was not significant in this sample, however. The probability of relapse was ≈15% and was lower in cases with lower IBMTR risk factors (NS in this sample). Within the adult group (age = 16-67), age at transplantation was not significantly related to the probability of survival at 1 or 5 years. The difference in 1 year survival between recipients of grafts with < and grafts with ≥2.5 × 107 was not significant (28% vs. 34%). The absence of HLA rejection mismatches was significantly associated: with survival at 1 year (survival = 68% vs. 27%, P = 0.005). Overall survival was 23% at 5 years. Engraftment and survival were significantly better in a group of 45 patients given a two-unit transplant, the majority of which also were treated with fludarabine-containing regimens. These results extend the data on adult recipients of cord blood grafts beyond those previously reported.

BACKGROUND:The causes of post-transfusion non-A, non-B hepatitis are still not fully defined, nor is it clear how accurate the tests are that are used to screen blood donors for hepatitis C virus (HCV) and to diagnose post-transfusion hepatitis caused by infected blood. METHODS:We used two first-generation enzyme-linked immunoassays (EIAs) and one second-generation immunoassay to test for anti-HCV antibodies in serum samples collected between 1976 and 1979 in the Transfusion-Transmitted Viruses Study (from 1247 patients who underwent transfusion and 1235 matched control subjects who did not receive transfusions). We tested serum collected before and after infection from the patients in whom non-A, non-B hepatitis developed, serum from their blood donors, and serum from 41 of the control subjects who had hepatitis unrelated to transfusion. RESULTS:Of the 115 patients in whom post-transfusion non-A, non-B hepatitis developed, the initial serum samples of 111 were anti-HCV-negative; after hepatitis developed in these 111 patients, the first-generation EIAs detected anti-HCV in 51 (46 percent), and the second-generation assay detected anti-HCV in an additional 16 (14 percent), for a total of 60 percent. Of 40 controls, 37 were anti-HCV-negative initially, and none seroconverted after hepatitis developed. If the 3 percent rate of non-A, non-B, non-C hepatitis among the controls (37 of 1235) was applied to the 1247 transfusion recipients, only 74 of the 111 cases of hepatitis were attributable to the transfusion. Thus, 91 percent (67 of 74) of the cases of post-transfusion hepatitis were caused by HCV. Of the 99 donors, 60 were HCV-positive (9 on second-generation tests only) and 39 were not. CONCLUSIONS:Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by HCV. Screening with a second-generation assay improves the rate of detection of HCV infection in patients with post-transfusion hepatitis and in blood donors. The use of this test showed a 3.6 percent risk of non-A, non-B, non-C hepatitis, which was not significantly different from the rate in the controls (3.0 percent).

It is essential for the development of strategies for prevention and therapy of human immunodeficiency virus (HIV-1) infections to define host factors playing a dominant role in determining the clinical outcome of infection. Antibodies directed against restricted regions of the HIV-1 glycoproteins gp120 and gp41 are likely to represent important factors involved in host defense against HIV-1. Definition of qualitative and quantitative differences in the spectrum of anti-gp120 and anti-gp41 antibodies between two vastly different groups of HIV-1-infected individuals, long-term asymptomatic carriers, and individuals with acquired immunodeficiency syndrome (AIDS) who died, might reveal the epitope specificity of antibodies contributing to prevention of clinical disease. To accomplish this goal, sera from both groups were assayed for antibodies recognizing synthetic peptides from gp120/gp41 which were shown in earlier experiments to mimic epitopes on the two HIV-1 glycoproteins. None of the sera recognized all of the distinct 27 peptides from gp120 and gp41. The spectrum of antibodies was distinct for each of the sera from both groups of HIV-1-infected individuals. Nevertheless, antibody responses distinguishing the two groups from each other were discerned. In particular, it was possible to predict the unfavorable outcome of disease by comparative measurements of levels of antibodies to a peptide (303-338), corresponding to the entire V3 hypervariable loop of gp120 and/or by providing evidence for declining levels of these antibodies during the course of infection. Antibodies recognizing additional peptides [(219-245), (280-306), (425-452), (658-682), (729-758), (808-845), and (845-862)] were significantly less prevalent in AIDS patients than in asymptomatic carriers. It appears possible that maintenance of high levels of the respective antibodies would contribute to preventing AIDS in HIV-1-infected individuals. Active immunization with antigens containing epitopes defined by the respective peptides and/or administration of the corresponding antibodies may be considered as a modality for therapy of HIV-1 infections.

Three injections of 10 μg/ml hepatitis B vaccine (Merck) given in the first week after birth, a month later and again at the age of six months to 63 neonates in a rural African population, elicited an antibody response in 93 per cent. The initial hepatitis B marker status of the babies and mothers did not influence the results at nine months. Side-effects were minor and we conclude that the vaccine can effectively and safely be used from birth in endemic situations.

A method is described for the isolation of immune complexes (IC) employing polyethylene glycol (PEG) precipitation and competitive binding to staphylococcal protein A (Staph A). Techniques for recovery of IC from Staph A were established using preformed IC of BSAanti-BSA. Studies in patients with hepatitis B systemic vasculitis revealed elevated levels of IC in serum, but levels did not correlate closely with disease activity. Analysis of IC in serum revealed both HBsAg and anti-HBs, whereas anti-HBs was not detectable in whole serum. The methodology described may have important application to immune complex diseases in which the inciting antigen is not known.

A total of 749 persistent carriers of hepatitis B surface antigen (HBsAg) were tested for hepatitis B e antigen/antibody to e antigen (HBeAg/anti-HBe) by a radioimmunoassay method. The prevalence of HBeAg was found to be: 9.1% in carrier-blood donors, 10.3% in mentally retarded patients without Down's syndrome, 23.6% in Chinese-Americans, 35.3% in drug addicts, 39.2% in mentally retarded patients with Down's syndrome, 61.4% in homosexual men, and 71.2% in dialysis patients. The prevalence of HBeAg appears to be independent of sex, race, and HBsAg antigenic subtype. Younger carries tend to be more frequently HBeAg positive than older ones. All individuals acutely infected with hepatitis B virus become at least transiently positive for HBeAg. Appearance or clearance of HBsAg, HBeAg and their corresponding antibodies seem to be interrelated.

Three sex and age matched groups of medical personnel, 20-40 individuals in each, received a course of hepatitis B vaccine: in one group the first dose of vaccine was given a month after injection of hepatitis B immune globulin; in the second, vaccine and immune globulin were given simultaneously; and, in the third, vaccine was given alone. The passively acquired antibody did not interfere with an active immune response to the vaccine. Both the timing of antibody appearance and the antibody titres were similar in the three groups, and the actively acquired antibody persisted for the 8 months of follow-up. Administration of the vaccine together with hepatitis B immune globulin will provide immediate protection, whereas people who receive vaccine alone may lack antibody for several months. This opens new possibilities for post-exposure prophylaxis.

A controlled, randomized, double-blind trial in 1,083 homosexual men from New York confirmed that a highly purified, formalin-inactivated vaccine against hepatitis B prepared from HBsAg positive plasma, is safe immunogenic, and highly efficacious. Over 95% of vaccinated subjects developed antibody against the surface antigen. Vaccine-induced antibody persisted for the entire 24-month follow-up period. The attack rate of all hepatitis B virus infections (excluding conversions of anti-HBc alone) was 3.2% in vaccine recipients compared with 25.6% in placebo recipients (p < 0.0001). In those who received all three doses of vaccine, of 40 μg each, the protective efficacy rate was close to 100%. The vaccine protects against acute hepatitis B, asymptomatic infection, and chronic antigenemia. There is reason to assume that the vaccine is also partially effective when given postexposure.

Three hundred thirty‐six medical personnel from hemodialysis centers were treated with three doses, 20 μg each, of the Merck hepatitis B vaccine (at 0, 1, and 6 months). Within 1 month after the first injection, 41% converted to anti‐HBs positivity; after the second injection the conversion rate rose to 80–90%; and after the booster, to 96–98%. The later rate remained unchanged during the 18‐month follow‐up period. Only 2.8% of those vaccinated did not respond to the vaccine. The patterns of immune responses to 20‐μg doses were found to be exactly the same as to 40‐μg doses. It is suggested that reduced doses of vaccine should be as efficacious as the larger ones.

Antibody to hepatitis B surface antigen (anti-HBs) developed within six months in 80% of haemodialysis patients given either two or three 40 μg doses of hepatitis B vaccine. A total of 89% had anti-HBs after a booster dose given six months later. Anti-HBs titres were higher in patients who received three initial doses than in those who received only two doses, but the proportion of anti-HBs-positive patients was the same in the two groups. Male patients became anti-HBs positive less often than females and their antibody titres were lower.