Development and operation of a program to obtain volunteer bone marrow donors unrelated to the patient

Because of recent increases in bone marrow transplantation, the lack of available matched sibling donors has become a problem. This study investigated the feasibility of obtaining volunteer bone marrow donors unrelated to the patient. A program was developed to inform potential donors and obtain their consent for listing in a bone marrow donor registry. Sixty-six percent of whole blood or apheresis donors agreed to participate in the program. There were no demographic differences between those who accepted or declined to participate. Religion, experiences with medical practices, and the attitude of the potential donor's spouse were important factors in the decision to participate. A search for donors was initiated for 127 patients. Thirty searches were not completed, primarily because of patient-related problems. A total of 713 HLA-A and -B antigen-identical donors was located for 63 of the 97 (65%) patients. A total of 40 HLA-A, -B, and -DR antigen-identical donors was located for 18 of these 63 patients. Six of these 18 patients then had one or more donors (total, 9) whose lymphocytes did not react in mixed lymphocyte culture. Thus, using the file of 2147 donors, an HLA-identical donor was located for 6 percent of the 97 patients. None of these patients has yet received a transplant; in four cases this was due to patient-related and in two cases donor-related reasons. The cost to establish the donor program averaged $33.46 (1984) per donor for donors already typed for HLA-A and -B antigens. This experience indicated that, given thorough information about bone marrow donation and transplantation, a majority of blood and apheresis donors will volunteer to donate bone marrow, without feeling pressure to do so. A relatively small donor file provided donors for 6 percent of patients. The long-term value of bone marrow transplantation using unrelated donors and the optimum size of the donor file remain to be established.     

Attitudes and physical condition of unrelated bone marrow donors immediately after donation

Annually, over 3000 bone marrow transplants are performed worldwide involving HLA-identical sibling donors. However, only 30 percent of those patients who need a bone marrow transplant have a matched sibling donor. Programs have been developed to provide volunteer unrelated bone marrow donors for patients without sibling donors. Because bone marrow donation requires a high level of altruism, especially on the part of a donor unrelated to the patient, it is important to determine the effect of donation on the donor. Serious medical complications during the collection of marrow from related donors have been reported only rarely, but there have been no reports on the psychosocial and physical effects of the bone marrow donation process on volunteer unrelated bone marrow donors. The first 20 unrelated volunteers who donated bone marrow through the authors' volunteer bone marrow donor program were surveyed. They suffered no serious emotional or physical aftereffects. Seventeen of 20 donors reported that making the decision to donate was easy, and 16 reported making the decision to donate right away. Nine of 20 donors, however, stated that a friend or family member discouraged them from donating. All 20 donors thought that they were well prepared for the donation process. Four donors thought that the donation process required more time than they expected, but four donors thought the reverse. One person thought the process was more painful than they expected; however, 12 found the process to be less painful than expected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recruiting blood donors into a local bone marrow donor registry

To date, most persons joining bone marrow donor registries have been recruited from platelet-pheresis panels. The potential of recruiting regular blood donors into bone marrow donor registry (BMDR) was explored. It was found that, with minimal effort, 6.2 percent of the age-eligible blood donors were recruited. A distinguishing feature of those who joined the BMDR was a history of frequent blood donations. Although local media attention had a major impact on recruitment, even those joining as a result of the publicity usually were regular blood donors. This program has the potential to recruit nearly 8000 volunteers from 120,000 regular blood donors over an 18-month period.     

The changing activities of a regional marrow donor program

BACKGROUND: A regional marrow donor program was established in 1982. Following the establishment of the National Marrow Donor Program (NMDP) in 1987, the activities of this regional program changed. STUDY DESIGN AND METHODS: To better understand the changes that occurred in the regional marrow donor program, its donor recruitment and marrow collection activities through 1991 were studied retrospectively. Data analyzed included the total number of potential donors, the number and types of potential donors recruited each year, the number of searches performed, the number of samples collected for HLA-DR typing and mixed lymphocyte culture testing, and the number of transplants in both programs from 1987 through 1991. Statistical analysis was performed by using chi-square. RESULTS: Initially, only persons who donated platelets by apheresis were enrolled into the program. In 1986, the regional program's first drive to recruit people who were not apheresis donors occurred. The number of such drives increased each year, and in 1991, 12 drives occurred, which resulted in the recruitment of 1313 potential marrow donors. From 1987 to 1991, the number of potential donors in the regional program grew from 3252 to 9146, but the proportion of apheresis donors in the program decreased. In 1987, 91.9 percent of marrow donors at the regional center had been apheresis donors, but in 1991, 41.7 percent had been apheresis donors. The number of marrows donated at the regional center increased from 11 in 1987 to 29 in 1989, but then fell to 24 per year in 1990 and 1991. The decrease in the number of donations at the regional program was due to the rapid growth in the NMDP file of potential marrow donors and the selection of donors whose HLA antigens were more compatible with those of the transplant recipients. In 1989, the regional program contained 4.6 percent of all HLA-A,B-typed and 11.2 percent of all HLA-A,B,DR-typed potential donors in the NMDP and collected 15.3 percent of all marrows. However, in 1991, the regional program contained 2.0 percent of HLA-A,B- typed donors and 4.1 percent of HLA-A,B,DR-typed donors and collected 5.3 percent of marrows. In 1987, 18 percent of the people who donated marrow at the regional center were phenotypically HLA-A,B,DR identical with the recipient, but in 1991, 92 percent of donor-recipient pairs were phenotypically HLA-A,B,DR identical. CONCLUSION: Recruitment activities became an increasingly larger part of the Regional Marrow Donor Program's activities. Increasing the size of the file of potential donors was necessary to maintain a constant number of donations. Persons who were not regular blood donors were an important part of the marrow donor program.     

Recruitment of unrelated persons as bone marrow donors. A preliminary experience

Seven hundred and sixty-three blood donors previously typed for HLA-A and B antigens were asked to consider donating bone marrow to unrelated patients for whom no HLA-matched sibling was available. Eighty-eight percent (668) indicated willingness to donate marrow, and of these, 615 (81%) participated in testing and 53 (7%) were unable to participate at the time of the request. Donors matched for HLA-A, B, C, and DR antigens and compatible in the mixed-leukocyte culture reaction were identified for 12 patients and eight transplants were performed. Engraftment was successful in all eight patients. In this article the factors considered in planning the program, the protocol eventually developed, the problems encountered, and critical issues of informed consent and donor confidentiality are reviewed.     

Effect of HLA incompatibility in marrow transplantation from unrelated and HLA-mismatched related donors

Transplants from related donors who share one HLA haplotype and are variably matched with the recipient for HLA-A, B, or DRB1 loci on the unshared haplotype are associated with increased risks of graft failure and graft-versus-host disease (GVHD) that correlate with the degree of HLA mismatch. Survival, however, is not necessarily inferior if recipient incompatibility is limited to one HLA locus. Available methods for post-transplant immunosuppression have not allowed similar success with transplants incompatible for two or three HLA loci. GVHD incidence and severity can be decreased by depletion of donor T cells from the marrow inoculum. However, the potential benefit is offset by increased graft failure and leukemia relapse with no improvement in survival. Since fewer than 30% of the patients in North America or Europe have an HLA-matched sibling and less than 5% have a one HLA-locus mismatched relative, most candidates for an allogeneic marrow transplant are in need of an unrelated donor. As of October 1993, the National Marrow Donor Program (NMDP) has accrued more than 1 million volunteers typed for HLA-A and B, including 200,000 typed for HLA-DR, and has provided donors for more than 2000 transplants. The probability of finding an HLA-A, B, DR match at the initial search has increased from 10-15% in 1987, to 50-55% in 1992. An additional 12% of patients will find a match when available HLA-A and B matched donors are typed for DR, and 20% of patients have a one HLA-locus incompatible unrelated donor. Through an international network of regional registries a search for an unrelated donor can now be conducted among 1.7 million volunteers worldwide. Unrelated donor transplants have allowed long-term disease-free survival of patients with a variety of hematological disorders. When compared to HLA-matched sibling transplants, unrelated donor transplants are associated with an increase in the incidence of graft failure and GVHD. Such an increase may be due to undetected HLA disparities or to non-HLA-linked histocompatibility genes. At our center patients with CML in chronic phase, the most common indication for unrelated donor transplantation, have a 50-55% probability of survival 2-6 years after an unrelated donor transplant, whereas patients with aplastic or refractory anemia have a 25-35% probability of survival.(ABSTRACT TRUNCATED AT 400 WORDS)     

Strategies to recruit plateletpheresis donors from a registry of HLA- typed, unrelated, bone marrow donors

Rising demand for single-donor platelet components–from random donors, to maintain platelet inventories, or from HLA-compatible donors, to support alloimmune platelet-refractory patients–necessitated increasing the size of a community plateletpheresis donor registry. This study compares two strategies for recruiting whole-blood donors into a plateletpheresis program. The whole-blood donors who were asked to participate in this study had recently joined an unrelated bone marrow donor registry and had been HLA-typed as part of that process. An in-person recruitment strategy, which was time-intensive for the apheresis donor coordinator, served as the standard. A by-mail strategy involved the mailing of recruitment materials to marrow-donor registry participants. Marrow-donor registry participants were approached about apheresis participation after they had indicated an interest in the plateletpheresis program by returning a tear-off section of an informational brochure that was sent to them along with their marrow- donor registry materials. A total of 852 marrow-donor registry participants were randomly assigned to one of two recruitment strategies, and the recruitment rates were the same (46%) for both methods. In addition, levels of apheresis participation and attrition rates of donors recruited by either strategy were comparable. Thus, the simple strategy of mailing information about a plateletpheresis program is a very cost-effective method of recruiting donors.     

Evaluation and eligibility of HLA-identical sibling donors for stem cell/bone marrow donation

Overall, the number of allogeneic transplants performed world-wide has not increased dramatically over the past 5 years. However, the proportion of allogeneic transplants undertaken using peripheral blood progenitor cells (PBPCs) has risen significantly. Currently, as part of an ethically approved trial, potential donors are seen, assessed and consented by physicians not caring directly for the recipients. Thirty-five potential sibling donors were seen and assessed for their willingness and fitness to donate for 28 patients. One donor opted to give bone marrow and the rest selected PBPC donation. Seven of these donors were found to have concurrent medical conditions. Due to poor venous access, one donor was advised to donate bone marrow and two others donated bone marrow due to an underlying condition. Four others were deemed unfit for donation. Donation of stem cells from bone marrow or peripheral blood is not a risk-free procedure; careful preassessment and counselling is mandatory especially when the age of prospective patients and therefore donors is increasing.     

On willingness to be a bone marrow donor

The authors studied factors that may influence the willingness of apheresis donors to consider bone marrow donation to an unrelated recipient. Donors were sent questionnaires describing bone marrow transplantation and the role of the donor. The information about degree of risk to the donor was varied from low to high risk. Two other factors that might influence donor motivation also were presented: probability of actually being asked to participate (high or low), and "salience of responsibility," which defines the stress to donate based on the number of persons being asked (large or small group). The degree of risk presented strongly affected willingness to volunteer, but the two motivation factors had no effect. The factor of risk negatively affected women more than men, and negatively affected those with family responsibilities more than single donors. Other findings were: men were more willing then women to donate marrow; those with few donations were among the most willing; and those who knew others who had either needed or provided blood products were also among the most willing.     

Immune system changes in cytapheresis donors

In vitro measurements of several variables of the immune system were made in 21 healthy donors who had been subjected to frequent cytapheresis an a group of whole blood donor controls matched for age and sex. Significant changes noted in the apheresis donors compared to controls included a 23 percent lower mean absolute lymphocyte count (p less than .01), a 25 percent lower mean T cell count (p less than .01), and a 46 percent lower mean B cell count (p less than .001). Serum protein changes included a 27 percent lower mean gamma globulin level (p less than .01), and 14 percent lower mean IgG level (p less than .05) in the apheresis donors when compared to the control group. The possible implications of these findings are discussed, and we suggest that donors undergoing multiple cytapheresis procedures be closely monitored to determine the safe donation frequency.     

Return of autologous blood donors as homologous blood donors

Autologous blood donors (ABDs) have been reported to have favorable attitudes toward returning as homologous blood donors (HBDs), but the frequency of return has not been well documented. ABDs eligible by history to be HBDs were followed at one blood center: 255 donating for elective surgery and 234 donating during pregnancy were followed for an average of 18 months and 20 months, respectively, from time of eligibility after surgery or postpartum. Male ABDs had a higher rate of return as HBDs, as 34 percent (21/62) returned to donate an average of 3 units, whereas 13 percent (56/427) of female ABDs returned as HBDs to donate an average of 2 units. Although a history of donation was associated with a higher rate of return (30%, 34/113), 11 percent (43/376) of ABDs with no history as HBDs returned to donate homologous units, despite having been recruited less frequently than prior HBDs. Overall, all male ABDs and female ABDs with an HBD history returned most frequently. The extra effort required for an autologous donor program may result in the recruitment of new donors into the HBD pool.     

The use of granulocyte-colony-stimulating factor in volunteer unrelated hemopoietic stem cell donors.

Granulocyte-colony-stimulating factor (G-CSF) is used for the mobilization of hemopoietic stem cells in healthy donors. It has a number of common side effects such as bone pain, which resolve rapidly after administration is discontinued. Recent publications have raised concern that it might act as a trigger for the development of hematologic malignancy in susceptible individuals, possibly by causing genomic instability, but to date there is no evidence that healthy volunteer donors who receive G-CSF are at any increased risk. Ongoing studies aim to confirm whether or not G-CSF can cause chromosomal abnormalities in healthy donors. In the UK, the British Bone Marrow Registry and Anthony Nolan Trust give G-CSF to donors who have agreed to donate peripheral blood stem cells. It is recommended by the UK Registries at present that all stem cell donors are given updated information explaining the current uncertainties with regard to the use of G-CSF before they give informed consent to its administration. This information is based on a statement agreed by the World Marrow Donor Association for use by individual donor registries. Further, it is our current practice that all donors who have received G-CSF, as well as marrow donors who do not, should be under regular review for at least 10 years to allow the occurrence of any long-term adverse events to be documented.     

The use of granulocyte–colony-stimulating factor in volunteer unrelated hemopoietic stem cell donors

Granulocyte–colony-stimulating factor (G-CSF) is used for the mobilization of hemopoietic stem cells in healthy donors. It has a number of common side effects such as bone pain, which resolve rapidly after administration is discontinued. Recent publications have raised concern that it might act as a trigger for the development of hematologic malignancy in susceptible individuals, possibly by causing genomic instability, but to date there is no evidence that healthy volunteer donors who receive G-CSF are at any increased risk. Ongoing studies aim to confirm whether or not G-CSF can cause chromosomal abnormalities in healthy donors. In the UK, the British Bone Marrow Registry and Anthony Nolan Trust give G-CSF to donors who have agreed to donate peripheral blood stem cells. It is recommended by the UK Registries at present that all stem cell donors are given updated information explaining the current uncertainties with regard to the use of G-CSF before they give informed consent to its administration. This information is based on a statement agreed by the World Marrow Donor Association for use by individual donor registries. Further, it is our current practice that all donors who have received G-CSF, as well as marrow donors who do not, should be under regular review for at least 10 years to allow the occurrence of any long-term adverse events to be documented.     

Demographic characteristics and risks for transfusion-transmissible infection among blood donors in Xinjiang autonomous region, People's Republic of China

BACKGROUND: The recruitment and retention of voluntary, nonremunerated blood donors continues to be a challenge in China. Understanding donor demographics and donor characteristics is crucial for any blood center in developing strategies to recruit potential donors. STUDY DESIGN and METHODS: The study population included all 29,784 whole blood donors from January 1 to December 31, 2003, at the Urumqi City Blood Center or one of its mobile blood collection buses. Demographic data, location, and frequency of donation and results of testing for transfusion-transmissible infection (TTI) were evaluated. RESULTS: The typical blood donor in Urumqi is male, less than 36 years of age, and Han Chinese; has at least a high school education; is a first-time donor; and donated at a mobile blood collection bus. The majority, 71 percent, were first-time donors. Among all donors, the seroprevalence rate of TTI was 3.5 percent for first-time donors, 2.7 percent for donors who donated twice, and 2.1 percent for donors who had donated three or more times. Han Chinese had lower seroprevalence rates of TTIs than ethnic minorities. Lower seroprevalence rates of TTIs were found among donors at mobile buses than at the blood centers. CONCLUSION: Similar to other donor populations, higher rates of TTIs were observed among first-time donors, and the prevalence decreased among repeated donors. One possible strategy for improving the safety of the blood supply might be for the blood center to recruit a cadre of donors who donate repeatedly, instead of relying on campaigns to recruit new donors from workplaces at each donation cycle.     

Vasovagal reactions in apheresis donors

BACKGROUND: The incidence rate of vasovagal reactions (VVRs) in apheresis is known to be higher in women than in men donors. VVRs in women apheresis donors were therefore analyzed to find out possible factors for their high incidence. STUDY DESIGN AND METHODS: VVR incidence was compared between whole blood (WB) and apheresis donation in relation mainly to age and circulatory blood volume (CBV). In addition, blood pressure and pulse rate were measured during apheresis. RESULTS: In WB donors, the VVR incidence was 0.83 and 1.25 percent, while in apheresis donors it was 0.99 and 4.17 percent in men and women, respectively. The VVR incidence decreased with age in WB donors, but age dependence was very weak in apheresis donors. In elderly women, the incidence increased with repeating cycle of apheresis. There were three different patterns of pulse fluctuation during apheresis, that is, stable (type A), increased rate during blood withdrawal (type B), and irregular pattern (type C). Elderly women donors and donors who suffered from VVRs mostly showed type B fluctuation. There was no particular fluctuation in blood pressure in relation to apheresis cycles. CONCLUSION: The VVR incidence rate was particularly high in women apheresis donors over 45 years old and increased with repeating cycles of apheresis. Smaller CBV, high sensitivity of low-pressure baroreceptors, and citrate effects on cardiovascular reflex might be major factors involved in the high incidence of VVRs.     

Technical and safety aspects of blood and marrow transplantation using G-CSF mobilized family donors

An allogeneic transplantation programme using immunoselected blood progenitor and bone marrow CD34+ cells has been established. Thirteen healthy HLA-matched, MLC negative sibling donors received two doses of 5 micrograms kg-1 G-CSF (s.c. daily) for 5 days. On days 4 and 5, large-volume mononuclear cell aphereses were performed (COBE Spectra) and on day 5 one unit of autologous blood was obtained. Mononuclear cells were pooled and cryopreserved after CD34+ cell-immunoselection on day 5. Bone marrow (BM) of the same donors was procured under routine conditions 10-45 days later (median: 27 days). The final graft consisted of blood CD34+ cells with either complete BM (n = 5) or immunoselected BM CD34+ cells (n = 8). The present paper describes the progenitor cell mobilization and apheresis protocol and analyzes the cell loss by BM and peripheral blood progenitor cell (PBPC) donation. Considerably larger amounts of mononuclear cells (CD45+), T-lymphocytes (CD3+) and platelets were lost by the apheresis as compared to bone marrow without apparent immediate clinical consequences for the donors. Owing to cross-cellular contamination of the apheresis concentrate, blood platelet count (PC) significantly decreased (mean PC after the second apheresis 116 x 10 microL-1); furthermore on average 3.04 x 10(10) CD3+ cells were removed by two apheresis sessions. This loss did not lead to long-term total lymphocyte count changes (2370 microL-1 versus 1889 microL-1) as observed during the long-term follow-up of 7/13 donors (mean 290 days). Subjectively, the PBPC collections were better accepted than BM donations in all but one family donor.     

Clinical toxicity and laboratory effects of granulocyte-colony- stimulating factor (filgrastim) mobilization and blood stem cell apheresis from normal donors, and analysis of charges for the procedures

BACKGROUND: Apheresis of granulocyte-colony-stimulating factor (filgrastim)-mobilized blood stem cells from normal donors is now being used in place of a marrow harvest in transplantation. How the adverse effects of and charges for this procedure compare with those of the standard marrow harvest is not known. STUDY DESIGN AND METHODS: Forty consecutive normal subjects who received filgrastim 96 micrograms/kg) subcutaneously twice daily for 4 to 6 days in preparation for apheresis were monitored prospectively by clinical and laboratory evaluation. RESULTS: Sixty-two percent of the subjects required oral analgesics. None discontinued filgrastim prematurely. Bone pain (82%), headache (70%), fatigue (20%), and nausea (10%) were reported. Filgrastim caused a mean eightfold increase in neutrophil counts, a mean twofold increase in lymphocyte counts, a mean twofold rise in alkaline phosphatase and lactate dehydrogenase levels, and minor changes in serum potassium, magnesium, and uric acid. Adverse events and laboratory effects resolved within 7 days after apheresis. No apheresis stem cell donor required transfusion or hospitalization, and only one required an additional clinic visit after completion of apheresis. By comparison, a retrospective analysis of 33 normal marrow donors demonstrated that all received transfusion(s), 3 were hospitalized, 3 required additional clinic visits after the marrow harvest. The median total charges related to the two procedures were comparable (p = 0.43), although the charges were significantly lower for donors requiring only one apheresis procedure (p = 0.002). CONCLUSION: Filgrastim mobilization and apheresis of blood stem cells constitute a safe, well-tolerated, and comparable or less expensive alternative to the traditional marrow harvest.     

Racial and ethnic composition of volunteer cord blood donors: comparison with volunteer unrelated marrow donors

BACKGROUND: Umbilical cord blood is an alternative peripheral blood progenitor cell source for patients who need transplantation. A presumed advantage of cord blood is the ability to increase minority recruitment. STUDY DESIGN AND METHODS: The racial composition of five member cord blood banks of the National Marrow Donor Program (NMDP) was compared, representing 9020 cord blood donors with NMDP marrow donors from comparable geographic areas, representing 417,676 donors. Cord blood and marrow donors self-reported racial designations on questionnaires. Donor statistics were compared with baseline racial data of deliveries from participating hospitals for cord blood donors and with geographic census data for marrow donors. RESULTS: The California, Florida, and Massachusetts cord blood banks recruited a lower percentage of minorities than the corresponding marrow donor centers. In New York and Colorado, minority recruitment was equivalent. In California, Florida, Massachusetts, and New York, the cord blood banks recruited a lower percentage of minorities than those delivering at the respective hospitals. The cord blood banks in California, Colorado, Florida, and Massachusetts recruited a lower percentage of minorities compared with delivery data than the corresponding marrow donor centers compared with census population (p < 0.001). In New York, the percentages were similar. CONCLUSION: The problem of insufficient minority recruitment of cord blood has not yet been solved. Better strategies are needed to recruit minority donors.     

The first-year costs of establishing an unrelated bone marrow donor registry

The cost of therapies like bone marrow transplantation has been an important consideration for several decades. Bone marrow transplantation is becoming increasingly accepted as an effective treatment for hematologic disorders, including acute nonlymphocytic leukemia. To find suitable donors, bone marrow donor registries are being developed. The first-year costs of establishing an unrelated bone marrow donor registry are reported here. First-year costs are largely due to personnel costs and HLA typing charges. The cost per registrant decreases over time, but further decreases due to economies of scale are limited by the continued fixed requirement for HLA typing. Data are presented by separating costs into six unique categories, thereby allowing other blood centers to estimate start-up costs based on our experience.     

Red cell collection by apheresis technology

To determine the feasibility of collecting 2 units (450 mL) of red cells per donation by apheresis technology, apheresis red cell collections were compared to whole-blood donations. Forty blood donors were equally divided between the two study arms on the basis of gender and iron supplementation (650 mg ferrous gluconate/day vs. no supplementation). During the 1-year study period, the apheresis participants donated 450 mL of red cells three times, and the whole- blood donors gave 225 mL of red cells (1 unit of blood) on six occasions. There were no reported side effects during the 102 whole- blood donations, whereas symptoms were noted in 83 percent of the 59 apheresis procedures. The most common symptoms were numbness and tingling, which were relieved by a decrease in the plasma-return rate or by the administration of oral calcium supplements. Seven donors dropped out or were deferred during the study. Two whole-blood donors left with medical problems unrelated to the study, one apheresis donor and one whole-blood donor dropped out of the study because of excessive fatigue, and three non-iron-supplemented whole-blood donors had unacceptably low hematocrit levels. By the end of the study, 70 percent of the apheresis donors considered the procedure acceptable, 15 percent were undecided, and 15 percent thought it was not acceptable. As measures of iron balance, the serum ferritin and the red cell zinc protoporphyrin:heme ratios were significantly more abnormal in the non- iron-supplemented donors than in the iron-supplemented donors. However, there were no differences in iron balance according to the donation method.