[show abstract][hide abstract] ABSTRACT: 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.
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.
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 patient's 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.
Placental blood is a useful source of allogeneic hematopoietic stem cells for bone marrow reconstitution.
New England Journal of Medicine 12/1998; 339(22):1565-77. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 07/1997; 15(2):165-71.
[show abstract][hide abstract] ABSTRACT: Long-term nonprogressors (LTNPs) of human immunodeficiency virus type 1 (HIV-1) infection are characterized by low levels of HIV-1 replication and viral load. However, it has not been established whether they differ in this regard from progressors from the very early stage of infection. By studying peripheral blood mononuclear cell (PBMC) specimens from a longitudinally monitored cohort of HIV-1-infected men, we found that HIV-1 proviral copy numbers and HIV-1 mRNA expression levels as low or lower than those seen in seven carefully selected LTNPs were commonly observed in specimens collected soon after seroconversion from 28 subjects who became infected while under observation. However, only the LTNPs were able to stably maintain such an efficient viral control over time. Because of the instability of the early control of HIV-1 replication, the predictive value of HIV-1 mRNA expression in PBMCs at postseroconversion was found to be limited but significantly increased during the first year of infection. Besides their diagnostic implications, these data support the idea that LTNPs may be a pathophysiologically distinct subgroup among persons infected with HIV-1.
Journal of Virology 01/1997; 70(12):9035-40. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
AIDS 12/1996; 10(13):1555-61. · 6.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Several studies have shown that human immunodeficiency virus type 1 (HIV-1) is associated with an increase in the incidence of Kaposi's sarcoma and non-Hodgkin's lymphoma among homosexual men. The role of HIV-1 in increasing the incidence of other malignancies is more controversial. The incidence of non-Kaposi's sarcoma cancer was examined from 1978 to 1990 among 15,565 homosexual men who participated in studies of hepatitis B virus infection in the late 1970s in New York City, New York, and San Francisco, California. The standardized incidence ratio (SIR) for all cancers was 1.6 (95% confidence interval (CI) 1.4-1.8). Excesses were observed for non-Hodgkin's lymphoma (SIR = 12.7; 95% CI 11.0-14.6). Hodgkin's disease (SIR = 2.5; 95% CI 1.5-3.9), and anal cancer (SIR = 24.2 95% CI 13.5-39.9). As seen with non-Hodgkin's lymphoma, a cancer known to be associated with HIV-1. Hodgkin's disease incidence was significantly higher in more recent years compared with earlier years. No cases of Hodgkin's disease were found among HIV-1 antibody-negative men, and Hodgkin's disease was diagnosed near the time of initial acquired immunodeficiency syndrome diagnoses. Anal cancer incidence did not correlate with HIV-1 antibody status and did not tend to occur near the time of AIDS diagnoses. This study confirms the association of non-Hodgkin's lymphoma with HIV-1 infect on and suggests an association between Hodgkin's disease and HIV-1 infection. An excess in anal cancer was observed but did not appear to be associated with HIV-1 infection.
American Journal of Epidemiology 12/1996; 144(10):916-23. · 4.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: Clinical evidence of hematopoietic restoration with placental/umbilical cord blood (PCB) grafts indicates that PCB can be a useful source of hematopoietic stem cells for routine bone marrow reconstitution. In the unrelated setting, human leukocyte antigen (HLA)-matched donors must be obtained for candidate patients and, hence, large panels of frozen HLA-typed PCB units must be established. The large volume of unprocessed units, consisting mostly of red blood cells, plasma, and cryopreservation medium, poses a serious difficulty in this effort because storage space in liquid nitrogen is limited and costly. We report here that almost all the hematopoietic colony-forming cells present in PCB units can be recovered in a uniform volume of 20 ml by using rouleaux formation induced by hydroxyethyl starch and centrifugation to reduce the bulk of erythrocytes and plasma and, thus, concentrate leukocytes. This method multiples the number of units that can be stored in the same freezer space as much as 10-fold depending on the format of the storage system. We have also investigated the proportion of functional stem/progenitor cells initially present that are actually available to the recipient when thawed cryopreserved PCB units are infused. Progenitor cell viability is measurably decreased when thawed cells, still suspended in hypertonic cryopreservative solutions, are rapidly mixed with large volumes of isotonic solutions or plasma. The osmotic damage inflicted by the severe solute concentration gradient, however, can be averted by a simple 2-fold dilution after thawing, providing almost total recovery of viable hematopoietic progenitor cells.
Proceedings of the National Academy of Sciences 11/1995; 92(22):10119-22. · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: To establish human immunodeficiency virus type 1 (HIV-1) messenger RNA (mRNA) expression in peripheral blood mononuclear cells as a marker of risk for progression to the acquired immunodeficiency syndrome (AIDS) in a large cohort of HIV-infected persons followed for a prolonged period.
Retrospective testing of cryopreserved, coded specimens.
Research laboratories at the New York Blood Center and the Rockefeller University.
150 homosexual men infected with HIV-1 who did not have an AIDS diagnosis at the time of testing.
Multiply spliced and unspliced HIV-1 mRNAs in total peripheral blood mononuclear cell RNA were quantitated using reverse transcriptase-initiated polymerase chain reaction (PCR) and compared with other laboratory data and clinical outcome during the subsequent 8 years.
Although HIV-1 mRNA expression generally correlated with immunologic status, it was associated with future disease progression independently of CD4+ cell counts or their rate of decrease at the time of sampling. The association of HIV-1 mRNA with disease progression in persons with CD4+ cell counts higher than the median (> 624 cells/mm3) was particularly noteworthy; further variation in the CD4+ cell counts within this group was not prognostically significant.
The expression of HIV-1 mRNA in peripheral blood mononuclear cells is a strong independent marker for future HIV disease progression, even in persons with normal T-cell subsets.
Annals of internal medicine 11/1995; 123(9):641-8. · 13.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: The usefulness of placental/umbilical cord blood as a source of stem cells for marrow reconstitution of HLA-matched siblings has now been extended to the unrelated-donor setting. The need for HLA-matched donor tissue makes it essential to have available a frozen inventory of ready-to-use placental blood units. The New York Blood Center's Placental Blood Project, designed to evaluate the practical feasibility of unrelated placental blood transplantation, consists of four basic modules: collection of placental blood, maternal samples and donor data, accession and testing for genetic and infectious disease markers, freezing placental blood units, and data organization and retrieval. Additional modules include a computerized HLA matching algorithm and organization of data about patients requiring transplantation, which may be best taken up by organ-sharing organizations in the future. In this report, we describe the organization and discuss the methods and overall experience after collecting the first 1,000 units and supplying the tissue for the first two unrelated-donor placental blood transplants.
[show abstract][hide abstract] ABSTRACT: Homosexual/bisexual men from Amsterdam, The Netherlands, New York, New York, and San Francisco, California, were entered into trials of the efficacy of hepatitis B vaccine shortly before the acquired immunodeficiency syndrome (AIDS) epidemic was recognized (1978-1980). The authors analyzed data, including serial blood samples tested for antibody to human immunodeficiency virus type 1 (HIV-1) as well as demographic and behavioral information, to characterize the spread of HIV-1 infection within the cohorts. By the end of 1982, the cumulative incidence of HIV-1 infection within the cohorts. By the end of 1982, the cumulative incidence of HIV-1 infection was 7.5% in Amsterdam, 26.8% in New York City, and 42.6% in San Francisco. Covariate analysis showed that differences in sexual activity (number of male sexual partners) and correlates of sexual activity (age and hepatitis B incidence) accounted for the differences in incidence of HIV-1 infection between the New York City and San Francisco cohorts. These covariates did not explain the lower incidence in the Amsterdam cohort. In conclusion, significant differences were found in the spread of HIV-1 in cohorts of homosexual men in Amsterdam, New York City, and San Francisco. These dissimilarities were probably due to a combination of differences in sexual activity at the time the epidemic began and a later introduction of HIV-1 in Amsterdam.
American Journal of Epidemiology 05/1993; 137(8):909-15. · 4.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: Trends in mortality related to infection by human immunodeficiency virus type 1 (HIV-1) and to other causes were examined from 1978 to 1988 in a cohort of 8,906 homosexual men who participated in studies of hepatitis B virus infection in the late 1970s in New York City. HIV-related mortality rates increased from 1 per 10,000 person-years in 1980 to 181 per 10,000 person-years in 1986, followed by a plateau from 1986 to 1988. The standardized mortality ratio among white men in the cohort was 3.7 (95% confidence interval (Cl) 3.4-3.9) as compared with white men from across the United States. Higher HIV-related mortality rates were associated with a higher number of sexual partners, a history of gonorrhea and/or syphilis, and serologic markers of infection with hepatitis B virus. After adjustment for demographics and sexual behaviors, the relative risk of mortality for Hispanic men as compared with white men was 1.5 (95% Cl 1.1-1.9). This study illustrates the large excess in mortality among homosexual men over the last decade, with the excess accounted for by deaths from HIV-related diseases. The recent plateau in mortality may be due to the effect of new treatments and/or the decline in new HIV-1 infections among homosexual men. The excess in HIV-related mortality among Hispanic homosexual men was not explained by differences in demographics and factors associated with the sexual transmission of HIV-1.
American Journal of Epidemiology 10/1992; 136(6):646-56. · 4.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hepatitis B vaccine has been recommended for high-risk individuals in the United States for more than a decade. This targeted strategy, however, has failed to control hepatitis B virus (HBV) infection. Universal immunization is being considered as an alternative approach, in particular the inclusion of hepatitis B vaccine with routine childhood vaccinations. Data presented herein demonstrate a high degree of efficacy for hepatitis vaccine with hepatitis B immune globulin in preventing perinatal HBV infection in newborns. Immune response to vaccine was dependent in part on the dose administered, with some enhancement of response if the infant was older at the time of initial injection or if the booster dose was given later. Long-term follow-up showed persistence of vaccine-induced antibody for 5 to 10 years in 90% of immunized infants and adults. Only 3% to 5% of these high-risk individuals had serologic evidence of an HBV infection. None of the infections had been symptomatic and none resulted in a chronic HBV carrier state. Thus, immune responses and efficacy of hepatitis B vaccine in infants were excellent, and immunity and protection against clinically significant HBV infection persisted for at least 5 to 10 years, features essential to success of a program of universal childhood immunization against HBV.
[show abstract][hide abstract] ABSTRACT: This study examined the effect of duration of hepatitis B virus infection on the association between human immunodeficiency virus type-1 infection and hepatitis B viral replication. Twenty-five chronic HBsAg carriers were studied. Presence of hepatitis B virus DNA and expression of HBeAg were more frequent among 20 chronic HBsAg carriers positive for human immunodeficiency virus type-1 antibody compared with five chronic HBsAg carriers negative for human immunodeficiency virus type-1 antibody, but the associations were not statistically significant. Hepatitis B virus DNA and HBeAg were inversely related to duration of hepatitis B virus infection (p less than 0.001). Stratifying for duration of hepatitis B virus infection, the presence of viral replication was similar among patients negative and positive for antibody to human immunodeficiency virus type-1. Hepatitis B virus DNA levels did not increase with the decline of cellular immunity over time. In conclusion, hepatitis B virus replication among chronic carriers may be a function of duration of hepatitis B virus infection rather than of an effect of human immunodeficiency virus type-1.
[show abstract][hide abstract] ABSTRACT: Health-care workers have an occupational risk of infection with hepatitis C virus (HCV). However, neither the magnitude of this risk nor the practices associated with it have been defined. Since dentists have numerous patients and are exposed to blood, they are likely to have the maximum risk. Therefore, we have assessed occupational risk for HCV infection among dentists in the New York City area. Individuals who admitted present or previous intravenous drug use or (men) who were homosexual or bisexual were excluded. Demographic, occupational, and behavioural data were recorded, and sera were tested for antibodies to HCV (anti-HCV). Anti-HCV was found in 8 (1.75%) of 456 dentists compared with 1 (0.14%) of 723 controls (odds ratio [OR] 12.9, 95% confidence interval [CI] 1.7 to 573). Anti-HCV was found in 4 (9.3%) of 43 oral surgeons compared with 4 (0.97%) of 413 other dentists (OR 10.5, 95% CI 1.9 to 58). Seropositive dentists claimed to have treated more intravenous drug users in the week (p = 0.04) or month (p = 0.03) before the study than did seronegative dentists. Our findings show that dentists are at increased risk for hepatitis C infection. All health-care workers should regard patients as potentially infected with a communicable bloodborne agent.
The Lancet 12/1991; 338(8782-8783):1539-42. · 39.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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).
New England Journal of Medicine 12/1991; 325(19):1325-9. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
New England Journal of Medicine 12/1990; 323(19):1308-12. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: In a survey carried out from 1985 through 1986, volunteer blood donors to The Greater New York Blood Program were tested for two surrogate markers for non-A, non-B hepatitis--elevation of alanine aminotransferase level and presence of antibody to hepatitis B core antigen. Stored serum samples from selected donors were also recently tested for antibody to hepatitis C virus (anti-HCV). Anti-HCV was detected in 0.9% to 1.4% of donors and was higher in black and Hispanic donors than in white donors. Anti-HCV prevalence increased with increasing age through the fourth decade of life, but decreased thereafter, possibly reflecting the disappearance of detectable antibody with time. Anti-HCV correlated with both alanine aminotransferase level and the presence or absence of antibody to hepatitis B core antigen. These associations suggest that donor screening for elevation of alanine aminotransferase level and presence of antibody to hepatitis B core antigen was, as expected, at least partially effective in preventing transfusion-associated non-A, non-B hepatitis. The detection of anti-HCV in donors who have neither an elevation of alanine aminotransferase level nor presence of antibody to hepatitis B core antigen suggests that donor screening for anti-HCV will further reduce the risk of transfusion-associated hepatitis.
JAMA The Journal of the American Medical Association 02/1990; 263(1):49-53. · 29.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: We interviewed 51 blood donors in four major US metropolitan areas subsequently found to have had antibodies to human T-cell lymphotropic virus (anti-HTLV) in late 1984-early 1985. Sixteen donors (31%) reported that they or a sexual contact had a history of blood transfusion. Twelve donors (24%) reported that they or a sexual contact used intravenous drugs. Ten donors (20%) were blacks born in the southeastern US. Four of the male donors (15%) reported homosexual contact. The most common characteristic was an association with Japan or the Caribbean basin (61%). These results show a broader variation of epidemiologic backgrounds than anticipated.