A prospective, randomized clinical trial of universal WBC reduction
BACKGROUND Recipient exposure to allogeneic donor WBCs results in transfusion complications for selected populations of recipients. Whether or not WBC reduction should be universally applied is highly controversial. STUDY DESIGN AND METHODS In a general hospital, a randomized, controlled clinical trial of conversion to universal WBC reduction was conducted. Patients (11%) with established medical indications for WBC-reduced blood were not eligible. All other patients who required transfusion were assigned at random to receive either unmodified blood components or stored WBC-reduced RBCs and platelets. Analysis for each patient was restricted to the first hospitalization. RESULTS All eligible patients (n = 2780) were enrolled. Three specified primary outcome measures were not different between the two groups: 1) in-hospital mortality (8.5% control; 9.0% WBC-reduced; OR, 0.94 [95% CI, 0.72-1.22]; p = 0.64); 2) hospital length of stay (LOS) after transfusion (median number of days, 6.4 for control and 6.3 for WBC-reduced; p = 0.21); and 3) total hospital costs (median, $19,500 for control and $19,200 for WBC-reduced, p = 0.24). Secondary outcomes (intensive care LOS, postoperative LOS, antibiotic usage, and readmission rate) were not different between the two groups. Subgroup analysis based on patient age, sex, amount of blood transfused, or category of surgical procedure showed no effect of WBC reduction. Patients who received WBC-reduced blood had a lower incidence of febrile reactions (p = 0.06). CONCLUSION A beneficial effect of conversion from selective to universal WBC reduction was not demonstrated.
The transfusion trigger and number of units transfused in patients with HIV: associations with disease stage and functional status
BACKGROUND The influence of quality of life (QOL), physical functioning, and HIV disease stage on the transfusion trigger and the number of units transfused was investigated. STUDY DESIGN AND METHODS The Viral Activation Transfusion Study, a randomized, double-blind study at 11 participating sites, enrolled HIV-positive patients with anemia who required RBC transfusion; 428 patients were included in the analysis of the first transfusion. The QOL scores, Perceived Health Index, Karnofsky score, CD4+ cell count, HIV viral load, and site were analyzed for relationships with the Hb level and the number of units transfused. RESULTS The transfusion trigger was lower in patients with higher levels of Karnofsky score, Perceived Health Index, CD4+ cell count, and a number of QOL scales. Both the Hb trigger and the number of units transfused had a significant site variation. Males were transfused at a significantly lower Hb level than females. In multivariate analysis, the CD4+ cell count remained significant, but the Karnofsky score or the Perceived Health Index did not. The number of RBC units transfused was associated with the Hb level, CD4+ cell counts, and Karnofsky scores in unadjusted analysis but with only Hb in adjusted analysis. CONCLUSIONS In this group of HIV+ patients, lower CD4+ cell counts prompted transfusion at higher Hb levels. However, after controlling for the Hb level, the number of units transfused was associated with only the Hb level. The HIV stage appears to influence the decision to transfuse at a particular Hb level but not to influence the number of RBC units transfused. The functional status does not appear to influence the decision to transfuse.
Absence of HBV, HCV, HTLV and HHV-8 activation by allogeneic RBC transfusion of AIDS patients
Transfusion. 2002;42((9S):):23S.. Abstract No. S81-040C.
WBC reduction in RBC concentrates by prestorage filtration: multicenter experience
BACKGROUND As universal leukocyte (WBC) reduction (ULR) is being considered as a new standard, few data are available on the performance of WBC-reduction filtration in routine practice. The performance of WBC-reduction in RBCs, using varied filtration practices, in meeting the current FDA requirement (<5 x 10(6)), Council of Europe (EC) recommendation, the proposed FDA requirement (<1 x 10(6)), and a more stringent proposal (<5 x 10(5)) for residual WBCs per RBC unit was assessed and compared. STUDY DESIGN AND METHODS Participating facilities were the 11 sites of the Viral Activation Transfusion Study (VATS), a prospective study of the impact of transfusion with and without WBC-reduction on survival and HIV viral load in HIV-1-infected patients. Patients randomly assigned to undergo WBC reduction were required to receive RBCs < or =14 days old that had undergone prestorage (within 72 hours of collection) WBC-reduction filtration by a method devised to achieve a postfiltration WBC count of <5 x 10(6). Residual WBC quantitation was performed by PCR in the central VATS laboratory by using frozen WBC-reduced RBC samples obtained at issue for transfusion. RESULTS A total of 1869 WBC-reduced RBC units were studied. Filtration practices varied within and between sites. There were significant differences in mean residual WBC counts at the 11 sites (p<0.001). Among the WBC-reduced RBC units, 0.8 percent exceeded 5 x 10(6) WBCs per unit, 8.3 percent exceeded 1 x 10(6) WBCs per unit, and 14.3 percent exceeded 5 x 10(5) WBCs per unit. CONCLUSION Residual WBCs in WBC-reduced RBC units vary within and between sites. WBC reduction was successful, in that over 99 percent and 91 percent of VATS WBC-reduced RBC units met US and EC thresholds, respectively. However, the small but measurable failure rate indicates that not every unit will meet these guidelines.
A prospective randomized clinical trial of universal leukoreduction
Transfusion. 2001;41((Suppl):):1S.. Abstract No. P1-020B.
Survival of transfused donor white blood cells in HIV-infected recipients
The appearance and expansion of donor white blood cells in a recipient after transfusion has many potential biologic ramifications. Although patients with HIV infection are ostensibly at high risk for microchimerism, transfusion-associated graft-versus-host disease (TA-GVHD) is rare. The purpose of this study was to search for sustained microchimerism in such patients. Blood samples were collected from 93 HIV-infected women (a subset from the Viral Activation Transfusion Study, an NHLBI multicenter randomized trial comparing leukoreduced versus unmodified red blood cell [RBC] transfusions) before and after transfusions from male donors. Donor lymphocytes were detected in posttransfusion specimens using a quantitative Y-chromosome-specific polymerase chain reaction (PCR) assay, and donor-specific human leukocyte antigen (HLA) alleles were identified with allele-specific PCR primers and probes. Five of 47 subjects randomized to receive nonleukoreduced RBCs had detectable male lymphocytes 1 to 2 weeks after transfusion, but no subject had detectable male cells more than 4 weeks after a transfusion. In 4 subjects studied, donor-specific HLA haplotypes were detected in posttransfusion specimens, consistent with one or more donors' cells. None of 46 subjects randomized to receive leukoreduced RBCs had detectable male lymphocytes in the month after transfusion. Development of sustained microchimerism after transfusion in HIV-infected patients is rare; HIV-infected patients do not appear to be at risk for TA-GVHD.
Leukocyte-reduced red blood cell transfusions in patients with anemia and human immunodeficiency virus infection: the Viral Activation Transfusion Study: a randomized controlled trial
CONTEXT Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospective studies suggest that transfusions adversely affect the clinical course of HIV. Data in selected non-HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells (RBCs). OBJECTIVE To compare the effects of leukoreduced and unmodified RBC transfusions on survival, complications of acquired immunodeficiency syndrome, and relevant laboratory markers in HIV-infected patients. DESIGN AND SETTING Double-blind randomized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999, with a median follow-up of 12 months (24 months in survivors). PATIENTS A total of 531 persons infected with HIV and CMV, aged 14 years or older, who required transfusions for anemia; 259 received leukoreduced transfusions and 262 received unmodified transfusions (10 did not receive the planned transfusion). MAIN OUTCOME MEASURES Survival and change in plasma HIV RNA level 7 days after transfusion, compared by type of transfusion. RESULTS At entry, the groups were similar in demographic, clinical, and relevant laboratory characteristics. A total of 3864 RBC units were transfused. Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusion; 138 with unmodified transfusion); median survival was 13.0 and 20.5 months, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P =.12). Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction (RH, 1.35; 95% CI, 1.06-1.72). There was no difference in time to new opportunistic event/death or frequency of transfusion reactions. No changes in plasma HIV RNA level were seen in either group at days 7, 14, 21, or 28, even in patients not taking antiretroviral drugs. There were no differences in trends between groups in CMV DNA, CD4 cell counts, activated (CD38% or human leukocyte antigen-DR) CD8 cell counts, or plasma cytokine levels. CONCLUSIONS We found no evidence of HIV, CMV, or cytokine activation following blood transfusion in patients with advanced HIV infection. Leukoreduction provided no clinical benefit in these patients. These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different patient populations, since smaller studies in other patient populations have suggested leukoreduction may be beneficial.