The African American church as a donation site: motivations and barriers.

BACKGROUND: In the United States, African Americans donate at approximately half the rate of whites and therefore are underrepresented in the volunteer blood donor pool. The goal of this study was to identify motivators and barriers to African Americans donating blood. STUDY DESIGN AND METHODS: A consortium of 15 predominantly African American churches of varying denominations in metropolitan Atlanta, Georgia, participated in an 81-item self-administered survey. The questionnaire was designed to assess participant's demographic background, blood donation frequency, motivators and barriers to donation, knowledge and beliefs regarding donation, and overall health status. RESULTS: A total of 930 participants completed the survey: 72% female, 55% age 40 or older, 99% African American, and 58% college-educated. The most frequent reported motivators were donating to help save a life (96%) and donating because blood is needed (95%), while the most frequent barriers were that they rarely think about it and they were afraid, nervous, or anxious to give blood (35%). The association of barriers with donation status, age, gender, and education level was stronger than for motivators. Fear was more common in nondonors than lapsed and current donors, youngest compared to older adults, and women than men and less in those with higher income. CONCLUSION: Motivators and barriers to blood donation in African American church attendees differ depending on the respondents' demographics. To increase the effectiveness of church drives, donor recruitment should focus on addressing these barriers and motivators.

Demographic variations in blood donor deferrals in a major metropolitan area.

BACKGROUND: Presenting blood donors are screened to ensure both their safety and that of the recipients of blood products. Donors with identified risks are deferred from donating blood either temporarily or permanently. Minorities are underrepresented as donors in the United States and this may in part be a result of increased donor deferral rates in minorities compared to white individuals. STUDY DESIGN AND METHODS: Data consisted of deferred and successful blood donor presentations to the American Red Cross Southern Region in the metropolitan Atlanta area in 2004 to 2008. Bivariate and multivariate analyses were conducted by race/ethnicity, age group, and sex. RESULTS: A total of 586,159 voluntary donor presentations occurred in 2004 to 2008, of which 79,214 (15.6%) resulted in deferral. In the age 16 to 69 years subset (98.3% of the presentations), deferred presentations were mostly women (78.2%). The most common reason for donor deferral was low hemoglobin (62.6%). The donor deferral rate varied by race/ethnicity, age, and sex: whites (11.1%), Hispanics (14.1%), and African Americans (17.9%); 16- to 19-year-olds (17.0%) and 50- to 59-year-olds (11.7%); and females (20.0%) and males (6.2%). Compared to whites and Hispanics, African American females had the highest deferral rate in each age group. CONCLUSIONS: Minorities are disproportionately impacted by blood donor deferrals. Methods to decrease blood donor deferral rates among African Americans are needed.

Minimal toxicity and mortality in high-risk breast cancer patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin plus autologous marrow/stem-cell transplantation and comprehensive supportive care.

PURPOSE: To assess the clinical toxicity and outcome associated with a comprehensive supportive care approach in poor-risk breast cancer (BrCA) patients with high-dose chemotherapy (HDC). PATIENTS AND METHODS: One hundred twenty-five consecutive patients with stages II, III or metastatic breast cancer received HDC between February 1992 and June 1994. Recipients received 4 days of continuous infusion of cyclophosphamide 1.5 g/m2/d, thiotepa 125 mg/m2/d, and carboplatin 200 mg/m2/d followed by infusion of bone marrow or peripheral-blood stem cells (PBSC) and recombinant human growth factor (rhu-GF) support. Patients received similar supportive care that included administration of prophylactic antibiotics, management of neutropenic fevers, and transfusion support. RESULTS: There were 38 women with stage II or III (27 patients with > or = 10 lymph nodes), four with stage IIIB, and 83 with metastatic breast cancer. The median age was 44 years (range, 27 to 61). Grade II or greater nonhematologic toxicities included diarrhea (66%), stomatitis (33%), hepatic venoocclusive disease (VOD) (5%), and pulmonary toxicity (4%). Myeloid and platelet engraftment was comparable between bone marrow and PBSC recipients (P > .1). Infectious complications were rare and consisted of gram-negative bacteremia (1.6%), gram-positive bacteremia (1.6%), fungemia (1.6%), and documented or suspected aspergillosis infection (3%). There was one treatment-related death secondary to severe VOD. CONCLUSION: A comprehensive supportive care approach was associated with a low treatment-related mortality rate of less than 1%. With the observed reduction in treatment-related mortality, it is reasonable to evaluate the efficacy of HDC in women with less than 10 positive nodes and stage II disease in well-designed clinical trials.

Peripheral blood stem cell acquisition by large-volume leukapheresis in growth factor-stimulated and unstimulated rhesus monkeys: development of an animal model.

Twelve (eight unstimulated [UNS], four growth factor-stimulated [ST]) anesthetized adult male rhesus monkeys underwent a single large-volume leukapheresis (> 3 blood volumes processed) in an attempt to define an animal model for use in future peripheral blood stem cell (PBSC) transplantation studies. The cell separator was primed with autologous blood and saline and set according to the manufacturer's mononuclear cell (MNC) protocol using the granulocyte separation and small volume collection chambers with additional modifications. Stimulated animals received 5 micrograms/kg recombinant human interleukin-3 (rhIL-3) on days -12 to -5, 5 micrograms/kg granulocyte-macrophage colony-stimulating factor (GM-CSF) on days -4 to -1, and large-volume leukapheresis on day 0. UNS animals did not receive growth factors. Vascular access was via a triple lumen intra-aortic catheter; blood pressure was monitored via the third lumen. Pre- and post-apheresis blood counts were determined and product hematocrit (Hct), MNC, colony-forming units-granulocyte/macrophage (CFU-GM), CD34+, and lymphocyte subsets were studied. During the 100-minute large-volume leukapheresis with mean flow rate 26.4 +/- 3.9 mL/min, the pre- and post-Hct were 36.6 +/- 2.6 and 32.3 +/- 7.0%, platelets 447 +/- 305 and 154 +/- 77 x 10(9)/L, and MNC 2.7 +/- 0.9 and 1.9 +/- 1.4 x 10(9)/L (all p < .05) in UNS animals. In ST animals, the pre- and post-Hct were 39.0 +/- 5.6 and 34.9 +/- 3.7%, platelets 507 +/- 100 and 150 +/- 9 x 10(9)/L (p < .05), and MNC 4.9 +/- 1.6 and 2.8 +/- 0.7 x 10(9)/L (p < .05). The product contained 98.5 +/- 1.4% MNC, 4.1 +/- 4.1% Hct, 1.9 +/- 0.6 x 10(9) MNC, 9.2 +/- 7.3 x 10(4) CFU-GM, and 3.5 +/- 2.1 x 10(6) CD34+ cells in UNS animals. In ST monkeys, the product contained 49.5 +/- 32% MNC, 6.4 +/- 4.4% Hct, 3.6 +/- 1.8 x 10(9) MNC, 49.3 +/- 39 x 10(4) CFU-GM, and 9.1 +/- 5.5 x 10(6) CD34+ cells. Greater than 75% of the product MNC were CD2+ T cells in ST and UNS animals. Large-volume leukapheresis in rhesus monkeys was tolerated well. Herein we characterize an animal model for large-volume leukapheresis in UNS monkeys that is similar to that of human PBSC leukapheresis. In ST animals there is more than a five-fold increase in CFU-GM collected and an increase in circulating CFU-GM/MNC.(ABSTRACT TRUNCATED AT 400 WORDS)

In vitro and in vivo responses to interleukin 12 are maintained until the late SIV infection stage but lost during AIDS.

The in vitro proliferative responses of macaque peripheral blood mononuclear cells (PBMCs) to IL-12 appeared similar before and early after SIV infection, whereas macaque PBMCs sampled during symptomatic stages of SIV infection showed markedly decreased responses. IL-12 was administered to SIVmac239-infected rhesus macaques either during the asymptomatic or the AIDS stage of infection in efforts to evaluate the effect of this cytokine on immune responses, viral loads, and hematopoietic functions in vivo. IFN-gamma secretion levels induced during the asymptomatic or early symptomatic phase were similar to preinfection induced levels, whereas in later AIDS stages this response was lost. The constitutive levels of other measured cytokines were not affected by IL-12 administration in vivo. The frequency and activity of circulating NK cells were markedly enhanced at early stages but not at symptomatic stages of SIV infection. pCTL frequencies were enhanced at early symptomatic stages but not at late AIDS stages. Despite its immunomodulatory effect, IL-12 did not seem to exacerbate or inhibit the replication of SIV in vivo, or the frequency of circulating infected lymphocytes. IL-12 administration was associated with a significant yet subclinical and transient decrease in hematocrit and hemoglobin levels without evidence of hemolysis, hemodilution, or reduction in the frequency of colony-forming unit potential of bone marrow CD34+ cells. This phenomenon may be explained by a functional inhibition of differentiation rather than an altered generation of bone marrow precursors. Thus, these results suggest that IL-12 may benefit HIV-1-infected patients only as long as their immune system retains its capability to respond to cytokine stimulation.

Molecular cloning and expression of rhesus macaque and sooty mangabey interleukin 16: biologic activity and effect on simian immunodeficiency virus infection and/or replication.

Interleukin 16 (IL-16) has been shown to diminish HIV and SIV replication through inhibition of HIV and SIV mRNA transcription. To evaluate its role further, we compared IL-16 cloned from disease-susceptible rhesus macaques and disease-resistant sooty mangabeys. Recombinant rhesus macaque (rr) IL-16 was compared with recombinant sooty mangabey (rm), human, and other nonhuman primate IL-16 sequences and evaluated for its ability to induce chemotaxis and inhibit the mixed lymphocyte response (MLR). Also, rrIL-16 and rmIL-16 were evaluated for suppression of SIVmac251, which replicates efficiently in T cells and monocyte/macrophages (dual tropic), and cloned SIVmac239, which replicates efficiently in T cells (T tropic). Sequence comparison of rrIL-16 and rmIL-16 with human IL-16 showed >97% amino acid identity. Biocharacterization of rrIL-16 revealed potent induction of chemotaxis (p < 0.05) and marked inhibition of MLR (73 +/- 0.6%,p < 0.05) in rhesus and human cell systems. Using rrIL-16 and rmIL-16, p27 antigen production from PBMCs infected with SIVmac251 was decreased up to 70% (p < 0.05 and p < 0.01, respectively). In similar cultures infected with SIVmac239, rrIL-16 and rmIL-16 reduced p27 levels by 96 and 100%, respectively. These data demonstrate the biologic and antiviral functionality of rrIL-16 and rmIL-16.

Hematologic and virologic effects of lineage-specific and non-lineage-specific recombinant human and rhesus cytokines in a cohort of SIVmac239-infected macaques.

The hematologic abnormalities of SIV and HIV are well described, although the mechanisms that lead to hematopoietic dysfunction are yet to be fully defined. A number of growth factors and cytokines have been used to induce the differentiation, maturation, and proliferation of appropriate lineages, with the aim that such therapy will lead to functional hematopoietic reconstitution. Within this context, some cytokines have been shown to influence HIV and SIV replication in vitro and, in selected cases, in vivo. However, few studies detail the effects of hematopoietic cytokines such as IL-3, Flt-3 ligand, G-CSF, Tpo, and Epo or correlate the effects on virus replication. In an effort to address this issue, we infected 12 rhesus macaques with 500 TCID50 of SIVmac239 and intensively evaluated hematologic, virologic, and immunologic parameters during administration of cytokines. When all animals had lymphadenopathy, hepatosplenomegaly, and CD4+ cell counts > or =1000/microl, subgroups of three rhesus macaques were administered either rhFlt-3; rrIL-3a; combination of rhG-CSF, rhTpo, and rhEpo (rhGET); or rrIL-12. Fourteen days of rhFlt-3 administration induced expansion of the bone marrow CD34+ cells and granulocyte-macrophage colony-forming units (GM-CFUs) and increased absolute peripheral blood CD34+ cells and total CFUs. Following rrIL-3 and rhGET administration absolute peripheral blood CD34+ cells and total CFUs increased. rhGET also increased granulocyte, platelet, and reticulocyte counts by day 14 of administration. Branched DNA and coculture assays did not demonstrate any significant change in viral load with any of the cytokines administered. These data suggest that SIV-infected rhesus macaques have the hematopoietic capability to expand and mobilize CD34+ and GM-CFU progenitors and formed elements at 6-8 months postinfection in response to various cytokines, without increasing viral load.

Allogeneic bone marrow transplantation with matched unrelated donors for patients with hematologic malignancies using a preparative regimen of high-dose cyclophosphamide and fractionated total body irradiation.

Allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling donor is effective therapy for patients with bone marrow failure states and those with hematologic malignancies. However, only a minority of them will have an HLA-identical sibling donor; unrelated donors, matched or partially mismatched, have been used successfully for patients lacking a related donor. Even though results with allogeneic transplants using unrelated donors are encouraging, the incidence of complications including graft-versus-host disease (GVHD) and graft rejection or late graft failure is increased compared to identical sibling transplants. The combination of cyclophosphamide and total body irradiation (TBI) has been used as an effective preparative regimen for allogeneic transplants, however, the total dosage and dosing schedule of both the cyclophosphamide and TBI has varied significantly among studies. To decrease the rate of graft rejection and late graft failure with volunteer donors, we evaluated a preparative regimen of high-dose cyclophosphamide (200 mg/kg over 4 consecutive days, days -8, -7, -6, -5) followed by fractionated TBI (1400 cGy administered in eight fractions over 4 days, days -4, -3, -2, -1). GVHD prophylaxis included FK506 and methotrexate. From July 1993 to January 1996, 43 adult patients, median age 38 years (range 18-58 years), were treated with this preparative regimen. Seventeen patients had low-risk disease and 26 had high-risk disease. Thirty-one donor/recipient pairs were matched for HLA-A, -B, and -DR by serology and molecular typing. Seven additional pairs were minor mismatched at the HLA-A or HLA-B loci. Four other donor/recipient pairs were HLA-A,-B, and -DR identical by serology but allele mismatched at either DRB1 or DQB. Forty patients were evaluable for myeloid engraftment. Engraftment occurred in all 40 patients at a median of 19 days. There were no cases of graft rejection or late graft failure. Nephrotoxicity was the primary adverse event with 26 patients (60%) experiencing a doubling of their creatinine. Hepatic veno-occlusive disease occurred in seven patients, six of whom had high-risk disease. All patients who had relapsed or refractory disease prior to BMT achieved a complete remission following BMT. Six patients transplanted for high-risk disease relapsed a median of 377 days post-BMT. None of the patients with low-risk disease have relapsed following transplant; the Kaplan-Meier survival for those patients with low-risk disease is 62% and 37% for those patients transplanted with high-risk disease (P = 0.0129). The median Karnofsky performance status is 100% (range 70-100%). Therefore, a preparative regimen of high-dose cyclophosphamide and fractionated TBI is an acceptable regimen for patients receiving an allograft from unrelated donors.

Association of busulfan area under the curve with veno-occlusive disease following BMT.

Busulfan pharmacokinetics, specifically area under the concentration curve (AUC), have been correlated with the occurrence of veno-occlusive disease (VOD) following BMT. To evaluate the risk of VOD, we studied 66 patients who received pharmacotherapeutically monitored busulfan regimens in combination with CY, etoposide (VP16) and/or Ara-C in preparation for BMT. These patients received a total of 16 doses of busulfan dosed as 1 mg/kg/dose q 6 h beginning at 09.00 (n = 39), 18.00 (n = 2), 21.00 (n = 1) or 24.00 (n = 24) h. With the first dose, blood samples were obtained at baseline, every 15-30 min for 2 h, then every 1-2 h for 4 h. Blood was analyzed for busulfan concentration by high performance liquid chromatography and AUC calculated by the trapezoidal rule. Seventeen patients (25.8%) were not evaluable for AUC calculation due to slow absorption and/or elimination: 13 of 27 (48.1%) received the first dose between 18.00-24.00 vs four of 39 (10.2%) patients who received the first dose at 09.00 (P < 0.001). Eighteen of 51 (35.3%) evaluable patients had an AUC > 1500 mumol x min/l; 10 of whom received doses reduced proportionally to achieve an AUC = 1200 mumol x min/l starting with the 10th to 15th dose. Six of 18 (33.3%) patients with an initial AUC > 1500 mumol x min/l developed VOD vs one of 33 (3.0%) patients with an initial AUC < 1500 mumol x min/l (relative risk = 11.1; P = 0.0056). Other pharmacokinetic parameters, age, gender, type of BMT, previous therapy or pre-transplant liver function tests were not predictive of VOD. A higher incidence of VOD occurred in patients receiving BUCY (4 of 10) compared to those receiving BUCYAra-C (1 of 18) or BUCYVP16 (7 of 38), which could not be attributed to increased busulfan exposure in the BUCY patients. Routine pharmacotherapeutic monitoring of busulfan is recommended with further study to evaluate the impact of earlier and greater overall dose reduction in patients with high initial busulfan exposures.

EDTA-dependent leukoagglutination.

Leukopenia (WBC 1.9 x 10(9)/L) was reported from an automated cell counter (TOA E-5,000, Symex) on a patient blood sample collected in ethylene diamine tetracetic acid (EDTA). Leukocyte aggregates of 30-50 cells were seen on the peripheral blood smear. Blood samples collected in heparin, citrate, and EDTA had white blood counts (WBC) of 8.1, 8.1, and 2.5 x 10(9)/L. A 0.3-mL aliquot of patient EDTA-plasma mixed with 0.3 mL normal packed cells (NPC) resulted in a WBC of 2.7 x 10(9)/L, a reduction of 58% from the control value. Increasing concentrations of EDTA (0.35-2.16 mg/mL), patient serum, and NPC resulted in a greater than 60% WBC reduction at EDTA concentrations greater than 0.96 mg/mL. Serial dilutions of patient serum in phosphate buffered saline (PBS) showed greater than 50% WBC reduction at a dilution of 1:4. Incubation (0, 1, and 2 hours) (0 degrees C, room temperature [RT], and 37 degrees C) of samples containing patient serum, EDTA, and NPC resulted in the greatest WBC reduction at 2 hours and at RT (60%). Incubation with 0.01 M dithiothreitol (DTT) abolished the ability of patient serum to decrease the WBC. These data suggest an EDTA-dependent, low titer IgM leukoagglutinin.

Comparable safety of blood collection in "high-risk" autologous donors versus non-high-risk autologous and directed donors in a hospital setting.

The safety of autologous blood donation by "high-risk" patients (those with some preexisting medical conditions) has been questioned. The authors reviewed 1393 consecutive blood donation records (207 high-risk autologous [HRA], 665 non-high-risk autologous [NHRA], and 521 directed donors [DD]) to determine the safety and outcome of blood donation by HRA patients as compared with other donors at their center. The HRA group included patients with a history of significant coronary artery on cerebral vascular disease, recent seizures, cardiac arrhythmia, chronic heart failure, valvular or congenital heart disease, symptomatic dyspnea, insulin-dependent diabetes and/or current therapy with two or more antihypertensive medications. Those designated NHRA were all other autologous donors; DD met all criteria for homologous donation. Donor characteristics including predonation hematocrit, pre- and postdonation mean arterial pressure and heart rates were similar in all groups. Eight HRA donors (3.9%) had reactions, compared with 21 NHRA (3.2%) and 23 DD (4.4%), a difference that was without statistical significance. The reaction rate in all autologous donors (HRA and NHRA) was 3.4%. No differences in symptoms reported, hemodynamics or reaction severity were observed among the three groups (P > .05). A multiple logistic regression was performed within and among the groups with the risk factor categories listed above and medication classes including beta blockers, cardiac glycosides, calcium-channel blockers, antihypertensive agents, nitrates, and antiarrhythmic agents (chi 2 = 14.9; P = .0006). Only first-time donation (P = .0001) and cardiac glycoside usage (P = .04) were positively associated with an untoward reaction. The authors conclude that donation by HRA donors is at least as safe as that by donors who meet homologous donation criteria in their population and setting.

Donor origin Rh antibodies as a cause of significant hemolysis following ABO-identical orthotopic liver transplantation.

A group A, D-positive patient underwent orthotopic liver transplantation from a group A, D-negative (cde/cde) donor. Anti-D and -E were eluted from the recipient's red cells and were found in the recipient's serum 13 days later, at which time significant hemolysis developed. These Rh antibodies appear to he secondary to passive transfer of sensitized donor lymphocytes, a rare finding following liver transplantation.

Case report and review: alloimmunization, delayed hemolytic transfusion reaction, and clinically significant anti-Yt(a) in a patient with Beta-thalassemia/sickle cell anemia.

A 26-year-old female with Beta-thalassemia/sickle cell anemia was admitted to the hospital with symptoms of a painful crisis. During the next 4 days her hematocrit decreased to 13 percent, and there was reticulocytopenia. She was transfused with four units of red blood cells that were microscopically incompatible, and the hematocrit increased to 29 percent. Eight days later the patient was readmitted with back pain, hemoglobinuria, and a hematocrit of 27 percent. Anti-E, -c, -Jka, and -Yta were identified. The direct antiglobulin test was positive, and the eluate contained anti-c and -Jka. The patient's hematocrit continued to decrease to 14 percent. Transfusions were withheld and the patient recovered uneventfully. Separate 51Cr red blood cell survival studies showed significantly shortened survival of both autologous and R(1)R(1), Jk(a-), Yt(a+) erythrocytes. This case illustrates the complexity of transfusion management in hemoglobinopathy patients.