Patricia E. Taylor

Outcomes among 562 Recipients of Placental-Blood Transplants from Unrelated Donors

BACKGROUND A program for banking, characterizing, and distributing placental blood, also called umbilical-cord blood, for transplantation provided grafts for 562 patients between August 24, 1992, and January 30, 1998. We evaluated this experience. METHODS Placental blood was stored under liquid nitrogen and selected for specific patients on the basis of HLA type and leukocyte content. Patients were prepared for the transplantation of allogeneic hematopoietic cells in the placental blood and received prophylaxis against graft-versus-host disease (GVHD) according to routine procedures at each center. RESULTS Outcomes at 100 days after transplantation were known for all 562 patients, and outcomes at 1 year for 94 percent of eligible recipients. The cumulative rates of engraftment among the recipients, according to actuarial analysis, were 81 percent by day 42 for neutrophils (median time to engraftment, 28 days) and 85 percent by day 180 for platelets (median, day 90). The speed of myeloid engraftment was associated primarily with the leukocyte content of the graft, whereas transplantation-related events were associated with the patients underlying disease and age, the number of leukocytes in the graft, the degree of HLA disparity, and the transplantation center. After engraftment, age, HLA disparity, and center were the primary predictors of outcome. Severe acute GVHD (grade III or IV) occurred in 23 percent of patients, and chronic GVHD occurred in 25 percent. The rate of relapse among recipients with leukemia was 9 percent within the first 100 days, 17 percent within 6 months, and 26 percent by 1 year. These rates were associated with the severity of GVHD, type of leukemia, and stage of the disease. CONCLUSIONS Placental blood is a useful source of allogeneic hematopoietic stem cells for bone marrow reconstitution.

Hepatitis B vaccine in patients receiving hemodialysis: immunogenicity and efficacy

We evaluated the immunogenicity and efficacy of hepatitis B vaccine (Heptavax-B) in a randomized, double-blind, placebo-controlled trial involving 1311 patients receiving hemodialysis in the United States. After three doses of vaccine (40 micrograms each) had been administered, 63 per cent of the patients were antibody-positive. After correction for possible passive transfer of antibodies by blood transfusion, only 50 per cent of vaccine recipients were considered vaccine responders. The incidence of hepatitis B viral infection during the 25 months of the trial was much lower than had been anticipated and was virtually the same in the vaccine and placebo recipients (6.4 and 5.4 per cent, respectively). Four cases of hepatitis B occurred in patients who had an apparent antibody response to the vaccine, but in each case either antibody had reached low or undetectable levels before hepatitis B surface antigen was detected or the patient had been receiving immunosuppressive therapy. This study did not demonstrate the efficacy of the vaccine in a population of patients receiving dialysis in whom both the rate of antibody response to hepatitis B vaccine and the viral attack rate were low. Other measures to control transmission of hepatitis B virus in dialysis units, including surveillance for hepatitis B surface antigen and isolation of patients who are positive for the antigen, must be continued.

Hepatitis B vaccine in medical staff of hemodialysis units: efficacy and subtype cross-protection.

We evaluated the efficacy of hepatitis B vaccine (Heptavax-B) containing only the ad subtype in a randomized, placebo-controlled, double-blind trial among 865 staff members of 43 hemodialysis units in the United States. Surface antibody developed in 92.6 per cent of the subjects after two doses of vaccine and in 96 per cent after the six-month booster. The incidence of infections with hepatitis B virus (with or without hepatitis) was 9.9 per cent in placebo recipients and 2.2 per cent in vaccine recipients (P less than 0.01). The two cases of hepatitis B among vaccine recipients did not occur in subjects in whom antibody had developed. In 81 per cent of the hepatitis events, the virus was of the ay subtype. The indicence of ay virus was 8.2 per cent among placebo recipients and 1.2 per cent among vaccine recipients (P less than 0.005). We conclude that these data confirm the efficacy of the vaccine and demonstrate subtype cross-protection.

Screening of Selected Male Blood Donors for p24 Antigen of Human Immunodeficiency Virus Type 1

BACKGROUND The p24 antigen of human immunodeficiency virus type 1 (HIV-1) is sometimes detected before antibody (anti-HIV-1) is detectable in the serum of recently infected persons. This has led to the consideration of p24-antigen testing for routine screening of blood donors. METHODS To estimate how many HIV-infected seronegative donors would be identified if p24-antigen screening was introduced, we tested selected donations from a repository of 200,000 serum samples from voluntary donors that was established in late 1984 and early 1985. The 8597 serum samples selected for p24-antigen screening were chosen because their donors had demographic characteristics known to be associated with a high prevalence of seropositivity. RESULTS The prevalence of anti-HIV-1 antibodies in the 1984-1985 serum samples selected for p24-antigen screening was 1.54 percent--more than 100 times the 0.012 percent prevalence in present-day donations in the United States. The antigen was detected in 15 of 132 serum samples (11.4 percent) from donors who had already been confirmed as seropositive. No instance of confirmed positivity for p24 antigen was found among the 8465 seronegative serum samples. CONCLUSIONS These data indicate that the yield of screening for p24 antigen in volunteer donors to identify HIV-1 carriers would be negligible. We therefore recommend against routine screening with currently available p24-antigen assays.

Willingness to participate in HIV-1 vaccine efficacy trials and the effect of media events among gay and bisexual men in New York City: Project ACHIEVE.

Efficacy trials of candidate HIV-1 vaccines require study populations at high risk of infection who adhere to study protocols and who are willing to participate. Data from HIV-1 antibody-negative men (n = 698) enrolled in Project ACHIEVE in New York City were analyzed to assess willingness to participate in efficacy trials, factors influencing willingness, and the effect on willingness of the June 1994 media events about the decision not to proceed with phase III trials and about breakthrough infections during phase I and II vaccine trials. Sixty-eight percent indicated they would definitely or probably be willing to participate. Men enrolled during the time of media events were significantly less willing compared with men enrolled during other periods. These men were also more likely to mention safety of the vaccine, fear or mistrust of research or government, and social risks as important factors in their decision compared with men enrolled during other periods. The most frequently cited motivator for participation was altruism (57%); the most frequently cited barriers were vaccine safety (36%) and vaccine-induced seropositivity (19%). A substantial proportion of this cohort was willing to participate in future vaccine efficacy trials. However, because willingness may be affected by issues of vaccine safety, vaccine-induced seropositivity, and media coverage of these issues, significant efforts are needed for participant and community education, and specific concerns must be addressed in the design and implementation of trials.

the feasibility of Hiv-1 vaccine efficacy trials among gay/bisexual men in New York City: Project Achieve

Objective: Candidate populations for HIV‐1 vaccine efficacy trials need to be at high risk of infection, adhere to study protocols and be willing to participate. The goal of Project ACHIEVE is to collect baseline data needed in order to prepare for vaccine efficacy trials among gay/bisexual men in New York City. Design and methods: HIV‐1 antibody‐negative men were recruited into a cohort study with follow‐up visits every 3 months (n = 622). Frequency of high‐risk behaviors and incidence of HIV‐1 seroconversion were measured. Results: Of 544 men reporting having had at least one partner in the previous 3 months who was HIV‐1 antibody‐positive or of unknown status at baseline, 49% reported receptive anal sex encounters. Thirty‐two per cent of these men reported the highest risk behavior, unprotected receptive anal sex. The follow‐up rate at 12 months was 81%. The incidence rate of infection was 2.9 per 100 person‐years (95% confidence interval: 1.7, 4.9). During follow‐up, declines were observed in the proportion of men with an HIV‐1 antibody‐positive partner and the proportion reporting unprotected receptive or insertive anal sex. HIV‐1 infection rates declined from 4.3 per 100 person‐years in the first 6 months to 1.6 per 100 person‐years by the 12‐month visit. Conclusions: Gay/bisexual men in New York City are still placing themselves at risk of HIV‐1 infection and may be a suitable population for future vaccine trials. Continued follow‐up is needed to further define the incidence over time, especially for the period after the initial 3 to 6 months when vaccines are most likely to be effective. Immediate prevention efforts need to target this population more effectively.

Human T-cell lymphotropic virus in volunteer blood donors

Serum samples collected in 1985 and 1986 from 18,257 donors to the Greater New York Blood Program were screened by enzyme‐linked immunoassay for antibody to human T‐cell lymphotropic virus (anti‐ HTLV). Fifteen samples (0.08%) were confirmed positive: 7 by radioimmunoprecipitation assay (RIPA) alone, 6 by Western blot alone, and 2 by combined results from both tests. One donor, whose original test result was uninterpretable because multiple nonspecific bands were present on RIPA, clearly tested positive on subsequent specimens. Follow‐up testing of individuals with this type of result may be needed to resolve their HTLV status. Anti‐HTLV prevalence increased with age and was significantly more common in black or Hispanic donors and in those born in the Caribbean than in other donors. All anti‐HTLV‐ positive donors were negative for antibody to HIV‐1, and only one donor (7% of those positive) would have been excluded by any of the routine donor screening tests used at that time.

Eradicating hepatitis B virus: The critical role of preventing perinatal transmission

Prevention of hepatitis B virus (HBV) transmission from infected mothers to their newborns is critical to HBV control and eventual eradication. Mother-to-child perinatal transmission causes the highest chronic carrier rate (>85%) with a high rate of subsequent chronic liver disease and hepatocellular carcinoma. This risk is reduced by 90% with HBV vaccine given along with hepatitis B immune globulin (HBIG) starting at birth. New analyses of our data from US trials of HBIG and HBV vaccine in high-risk infants revealed better efficacy with yeast-recombinant vaccine than plasma-derived vaccine, especially in preventing late onset infections, with evidence that vaccine prevented transmission of maternal HBV infection with the glycine to arginine mutation in surface antigen codon 145 (sG145R). Most late infections with sG145R were in vaccine non-responders, suggesting escape from HBIG rather than from vaccine-induced antibody. Our findings also help explain survey results from Taiwan following universal childhood immunization implemented in the mid-1980s. We conclude that current vaccines will remain effective against surface antigen mutants. Anti-viral drugs in high-risk pregnant women, in combination with newborn HBIG and vaccine, show promise for eliminating residual breakthrough neonatal infections, critical to meeting WHO 2030 goals and for eradicating HBV.

A study of hepatitis A virus infection among hemophilia patients in New York City

To the Editor: Patients at our institution requiring ongoing red cell (RBC) transfusions for nonmalignant hematologic disease (thalassemia. sickle cell anemia) were switched in February 1992 from receiving washed RBCs to receiving RBCs transfused through high-efficiency bedside white cell (WBC)-reduction filters. This change occurred without incident. Shortly after a change to the use of a filter from a different manufacturer, a number of patients, particularly children, began to complain of infusion site pain. The pain was of sufficient severity to necessitate continuous use of a heating pad during transfusion. The rate of infusion was also slowed, and this unacceptably prolonged the time spent in the Dayward (outpatient clinic). In two extreme cases, patients were switched back to receiving washed RBCs. and the problem resolved. Infusion site pain has not previously been reported as a complication of the use of WBC-reduction filters. Since no change other than the filter was clearly associated with the complaints, we compared the frequency and intensity of infusion site pain using WBC-reduction filters from the two manufacturers in a group of eight patients (7 pediatric, 1 adult) given a total of 77 units of AS-3 (Nutricel) RBCs over a period of approximately 6 months. Of the 77 units transfused, 36 were given with one filter (RC50, Pall Biomedical Products Corp., Glen Cove, NY) and 41 with the other filter (Sepacell R500, Baxter Healthcare Corp., Deerfield, IL). Symptoms of pain were documented prospectively on the patients chart by the administering nurse in the Dayward and ranked by severity to range from no complaints (no pain) to itchy andlor burning but tolerable pain (mild pain), itchy and/or burning pain tolerable only with heating pad (moderate pain), and itchy and/or burning pain intolerable with heating pad (severe pain). Patients were unaware that a study was in progress. All patients received approximately equal numbers of RBC units through