Evaluation of Hematopoietic Stem Cell Donors by blindlove200

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									Transfusion Medicine
(with AABB)
Session Chair: Carolyn F. Whitsett, MD
Speakers: Mary M. Horowitz, MD, MS; Walter H. Dzik, MD; and Ira A. Shulman, MD




                  Evaluation of Hematopoietic Stem Cell Donors
                  Mary M. Horowitz and Dennis L. Confer


Donation of hematopoietic stem cells, either through           these risks. Additionally, donors and graft products
bone marrow or peripheral blood collection, is a               must be evaluated for the potential to transmit infec-
generally safe procedure for healthy donors. Serious           tions and other diseases to the recipient and to satisfy
adverse events are uncommon and death is exceed-               an increasing number of national and international
ingly rare. Nevertheless, all donors must be carefully         regulatory requirements. Donors must be able to
evaluated and fully informed prior to donation. This           provide informed consent without coercion or pres-
should be done by clinicians having good understand-           sure. Special attention to the clinical, psychological
ing of the potential physical and psychological compli-        and social needs of pediatric donors is necessary.
cations of donation and the factors that may increase


Hematopoietic stem cell (HSC) donors provide grafts for        recipient. HSC can transmit the same infectious agents trans-
>15,000 allogeneic hematopoietic stem cell transplants         missible by blood transfusion including hepatitis B virus
(HCT) annually, about 70% for related and 30% for unre-        (HBV), hepatitis C virus (HCV) and human immunodefi-
lated recipients. Until recently, bone marrow was the most     ciency virus (HIV). Additionally, some congenital or ac-
common graft source, but the use of cells collected from       quired conditions, such as genetic defects or immune defi-
peripheral blood has increased dramatically. Data from the     ciencies, are potentially transmissible. Assessing the risk of
Center for International Blood and Marrow Transplant           disease transmission requires a targeted screening history, a
Research (CIBMTR) indicate that peripheral blood collec-       search for physical signs of disease and laboratory testing
tions accounted for 75% of related and 50% of unrelated        for specific pathogens or traits.2 HSC donors should com-
donor donations in North America in 2003. Prospective          plete a questionnaire to elicit medical history and to iden-
donors must be evaluated to ensure that: 1) their cells are    tify behaviors associated with risk of disease transmission.3,4
suitable for transplantation in the recipient, 2) the dona-    Topics should include sexual behaviors, non-prescription
tion process will be safe for them, and 3) they understand     drug use, skin-breaching procedures, e.g., tattooing, and
fully what they are being asked to do.1                        residence in regions where exposure to malaria or the agent
                                                               of bovine spongiform encephalopathy (BSE) may occur.
Assessing the Donor for Risks to the Recipient                 Standardized questionnaires for assessing a prospective
There are numerous infectious agents that, if present in the   donor’s health history are freely available. The National
donor, pose definite or theoretical risk to the transplant     Marrow Donor Program (NMDP) maintains such a ques-
                                                               tionnaire, which is based upon a uniform donor question-
                                                               naire utilized in the blood banking field. The NMDP ques-
MMH: Center for International Blood and Marrow Transplant      tionnaire, comprised of 57 relevant questions for prospec-
Research, Medical College of Wisconsin, Milwaukee, WI          tive donor, is available in English and Spanish. Compan-
DLC: National Marrow Donor Program, Minneapolis, MN
                                                               ion documents provide rationale for the questioning and
Correspondence: Mary M. Horowitz, MD, MS, Medical College      recommendations for evaluation of responses. Copies of
of Wisconsin, 8701 Watertown Plank Road, Milwaukee WI          the NMDP forms are available at no charge from the NMDP
53226; Phone: (414) 456-8325, Fax: (414) 456-6530,             (www.marrow.org or 1-800-marrow2 in the US and 1-612-
marymh@mcw.edu                                                 627-5800 outside the US). A Uniform Donor History Ques-

Hematology 2005                                                                                                          469
tionnaire for Hematopoietic Progenitor Cells, Apheresis or       tive for WNV weeks before donation has ample opportu-
Marrow was recently drafted by an inter-organizational task      nity to become infected by the day of donation; while at
force to include requirements of the US Food and Drug            the same time, a donor who tests positive weeks before
Administration (FDA), the Foundation for the Accredita-          donation will likely be recovered by the time of donation.
tion of Cellular Therapy (FACT) and the American Asso-           In recognition of this dilemma, the NMDP implemented
ciation of Blood Banks (AABB). It can be viewed by visit-        WNV testing under IND on the actual day of donation,
ing www.factwebsite.org.                                         reasoning that while it might not be possible to prevent the
      Testing the donor’s blood, while important, cannot sub-    infusion of an infected product, knowing that a product
stitute for questioning because tests may be falsely nega-       was infected with WNV would provide an opportunity to
tive and available tests do not detect all potentially trans-    develop a preemptive treatment strategy, such as infusions
missible diseases. Positive responses on a screening ques-       of immune plasma. Fortunately, after testing well over 1000
tionnaire may lead to donor disqualification or, at a mini-      products for WNV, the NMDP has not encountered a single
mum, careful donor evaluation and a thorough assessment          positive result. It may be worth noting that this result—no
of risk versus benefit.                                          infections after more than 1000 tests—is expected because
      The donor physical examination should detect behav-        the point prevalence of WNV viremia among asymptom-
ioral and experiential stigmata, such as recent tattoos,         atic persons, even in the midst of a community epidemic, is
piercings, or signs of intravenous drug use, as well as signs    far less than 1 in 10,000.
of significant illnesses. Blood must be tested for, at least,         Donors with a confirmed positive test for HIV must not
the following infectious disease agents: human immuno-           donate. Donors with prior exposure to HBV and HCV may
deficiency virus 1 and 2 (HIV 1/2), HBV, HCV, Treponema          be used when there are no suitable alternatives. Strategies
pallidum, human T-cell lymphotrophic virus I and II (HTLV        for managing hepatitis exposure in donors and recipients
I/II) and cytomegalovirus (CMV). Recent FDA regulations          have been reviewed.5 When antibodies to HCV are detected,
require that these tests be done in a Clinical Laboratory        polymerase chain reaction (PCR) testing may be performed
Improvement Amendments (CLIA)-certified laboratory.              to detect HCV RNA. Failure to detect RNA, however, does
Results must be reviewed prior to initiating preparative         not preclude HCV transmission. Pretreatment of the donor
conditioning therapy in the recipient. If the time between       with interferon-α may be beneficial.5 Donors who have re-
initial donor evaluation and collection is delayed, repeat       covered from HBV infection can safely donate; HCT re-
testing may be necessary. It is also desirable to perform        cipients with active HBV infections may even benefit from
testing for prior infections with varicella-zoster virus (VZV)   having a donor with hepatitis B immunity.6 Transplant re-
and Epstein-Barr virus (EBV) and possibly others, such as        cipients whose donors are positive for hepatitis B surface
toxoplasmosis. Positive tests for exposure to these agents       Ag, however, are at high risk for post-transplant hepatic
may not preclude donation but may modify the transplant          complications and transplant-related mortality.7 CMV se-
approach or posttransplant surveillance strategies.              ronegative recipients may benefit from having CMV se-
      Emerging infectious diseases present unique problems       ronegative donors, though this is controversial and donor
for donor screening and qualification. Recent examples           CMV status correlates less strongly with recipient outcome
include the severe acute respiratory syndrome (SARS) and         than other donor characteristics like HLA-match and age.8
West Nile virus (WNV). In both of these instances, addi-         It has been suggested that CMV seropositive patients may
tional screening questions were emergently added to the          benefit from CMV seropositive donors.
donor qualification process in the US, based upon recom-
mendations from the FDA. In the case of WNV, the FDA also        Regulatory issues
encouraged industry to develop valid blood screening tests,      On May 25, 2005, the FDA implemented new regulations
which could be used to test donors for evidence of active        governing the manufacture of human products for trans-
infection. Currently, two blood screening tests for WNV          plantation and immune modulation, as well as a variety of
are available for use, but these tests remain under Investi-     other cellular- and tissue-based human products. These regu-
gational New Drug (IND) applications.                            lations are similar in some respects, but quite different in
      The situation with WNV is further complicated and          others, to regulations emerging in the European Union,
illustrates the difficulties that can occur in addressing new    Canada, Australia and elsewhere. The US regulations are
diseases. The problem with WNV is that, unlike CMV, HCV          founded on the FDA’s responsibility to limit the transmis-
and other viruses, the donor’s blood—and by inference,           sion of infectious diseases through the administration of
the cellular product—is only infectious during the viremic       human or human-derived products. From the transplant
phase of the illness, which has a rapid onset in the few days    physician’s perspective, they apply to peripheral blood stem
following an infected-mosquito bite. Individuals who have        cells, cord blood and donor lymphocytes; responsibility
developed antibodies to WNV are, for all intents, no longer      for bone marrow regulations has been assigned by the US
infectious. What this all means is that, to be informative,      Congress to the Health Resources and Services Adminis-
the testing for WNV must be performed concomitantly with         tration. The FDA regulations are comprehensive in their
product collection. For example, a donor who tests nega-         scope. They require that all facilities engaged in the “manu-

470                                                                                     American Society of Hematology
facture” of regulated products file a registration with the     than regional anesthesia, while fever and fainting are less
FDA. In addition, the regulations set requirements for es-      likely to occur after general anesthesia. Sixty-three percent
tablishing donor eligibility, for product documentation and     of 493 NMDP donors interviewed reported complete re-
labeling, for manufacturing facilities, and for product col-    covery within 14 days, and 24% between 2 weeks and 1
lection, processing, handling and transport (called Good        month after donation. Thirteen percent took more than a
Tissue Practices or GTPs).                                      month to feel fully recovered. Observations in related do-
     The US regulations, like those of other nations, apply     nors are similar, though more severe pain symptoms are
not only to products manufactured within the country, but       reported.
also to those that are imported from outside. Given the              Minor complications occur in 6% to 20% of marrow
extensive international collaboration and exchange of graft     donations. These include transient hypotension, syncope,
products necessary to provide suitable donors for patients      severe post-spinal headache, excess pain, unexpected hos-
in need, these provisions have the potential to create a        pitalization, and minor infections resolving within a few
regulatory grid-lock that could effectively stymie efforts      days of onset. Serious complications occur in 0.1%-0.3%
to facilitate HLA-matched transplants across international      of donations. The NMDP classifies major complications
borders. Fortunately, most regulatory agencies are quite        into 5 risk categories: anesthesia, infection, mechanical
aware of this potential problem and are working closely         injury, transfusion and others. Anesthesia risks generally
with national registries, such as the NMDP, and with the        involve reactions to anesthetic agents, including hyper-
World Marrow Donor Association (WMDA) to develop and            sensitivity reactions, malignant hyperthermia and arrhyth-
establish appropriate solutions. In addition to the FDA, or-    mias. Rarely, there are problems with intubation, such as
ganizations that can provide additional insight into US         laryngospasm, or with intravenous catheter insertion. Hy-
regulations include the AABB, the American Society for          potension may develop from anesthetic-related vaso-
Blood and Marrow Transplant (ASBMT), the International          dilatation and/or from volume depletion. Infections may
Society for Cellular Therapy (ISCT), and the NMDP. An-          occur at sites of marrow collection or line insertions. Infec-
other good source of information related to international       tions at distant sites, e.g., pneumonia, are also reported.
regulations, and other aspects of donor identification, graft   Infection requires therapy with antibiotics, which may pro-
procurement and graft transport, particularly across inter-     duce adverse reactions. Mechanical injuries result from
national borders, can be found at the WMDA website,             direct damage of local tissues during the collection proce-
www.worldmarrow.org. The WMDA was founded in 1994               dure. These may include bone damage, nerve damage or
to address obstacles faced when transplantation involves        entry of a collection needle into a blood vessel, an organ or
donors and recipients in different countries. Today this        the spinal canal. Hemorrhage can create pain from com-
voluntary organization establishes international guidelines     pression of soft tissues. Visceral injuries are very rare. Many
for the collection and transfer of hematopoietic stem cells.    but not all marrow donors require post-donation blood
Members include donor registries, cord blood registries and
numerous individuals working together to advance hemato-
poietic stem cell transplantation.                              Table 1. Symptoms reported by National Marrow Donor
                                                                Program (NMDP) bone marrow donors. N = 9601
Adverse Events after HSC Donation
While HSC donation is a reasonably safe procedure, ad-                                   Women          Men
                                                                Symptom                 (n = 4106)   (n = 5495)
verse events do occur. It is essential that donors are as-
                                                                Tired*                    85%          76%
sessed to detect conditions that might increase risk of do-
                                                                Collection Site Pain*     78%          75%
nation to unacceptable levels. In order to perform an ad-
equate pre-donation assessment, and to adequately inform        Back Pain                 67%          68%
prospective donors about risks, it is necessary to under-       Nausea*                   63%          40%
stand the most common and the most serious potential ad-        Sore Throat*              62%          57%
verse events. These differ for marrow and peripheral blood      Pain Sitting*             62%          57%
collections.                                                    Lightheadedness*          53%          42%
                                                                Headache*                 40%          32%
Adverse events after marrow donation                            Vomiting*                 39%          17%
Almost all marrow donors report some symptoms after do-
                                                                IV Site Pain*             37%          23%
nation. Table 1 describes symptoms reported by 9601 in-
                                                                Fever                     22%          22%
dividuals donating marrow through the NMDP. Pain and
                                                                Bandage Pain*             19%          26%
fatigue are the most common. Among the first 493 NMDP
marrow donors, when surveyed 2 days after donation, 75%         Bleeding at Site*         10%           8%
reported fatigue, 68%, pain at the collection site and 52%,     Fainting*                  7%           5%
low back pain.9 Nausea, vomiting and sore throat are more
common following collections done with general rather           * P < 0.05 between men and women


Hematology 2005                                                                                                           471
transfusion and many donor complications reported in the         days after the last collection. Though serious hemorrhage
1980s related to infusion of allogeneic blood. These risks       secondary to thrombocytopenia has not been reported,
are now minimized as autologous blood has largely re-            avoiding aspirin during mobilization and collection, and
placed allogeneic blood for transfusion of both related and      non-steroidal anti-inflammatory drugs during collection,
unrelated marrow donors. Among 6277 NMDP marrow col-             is prudent.
lections, allogeneic blood was administered in only 16 in-            The most significant immediate problem encountered
stances (0.25%). In 7 of these, it was probably avoidable        by peripheral blood HSC donors is inadequate venous ac-
since the donor was asymptomatic and hemoglobin levels           cess. Central lines are required to perform apheresis in up to
were not prohibitively low. It is important to allow adequate    20% of collections.14 Central line complications are uncom-
time for autologous blood collection when planning the           mon but include pneumothorax, hemorrhage and infection.
pretransplant evaluation and the transplant procedure.                Filgrastim administration may precipitate severe sickle
                                                                 crisis in persons with sickle cell anemia or complex sickle
Adverse events after peripheral blood donation                   cell hemoglobinopathies.15,16 A 47-year-old woman with
Like marrow donors, most peripheral blood HSC donors             Hb SC disease, who had never had any symptoms from her
report symptoms.10-12 Most are related to hematopoietic          condition, suffered a fatal sickle crisis during filgrastim
growth factors, usually filgrastim (rhG-CSF, r-metHUG-           mobilization of HSC intended for her sister.15 It remains to
CSF), lenograstim (a glycosylated rhG-CSF formulation,           be clarified whether persons with sickle trait (Hb AS) are at
not marketed in the US) or sargramostim (rhGM-CSF), given        any increased risk from filgrastim. Kang et al safely mobi-
to increase the concentration of HSCs in the donor’s circu-      lized and collected cells from 9 donors with sickle trait.17
lation. Pegfilgrastim (PEG–G-CSF) has been used success-         These donors had higher symptom scores during mobiliza-
fully to mobilize cells for autologous transplantation in a      tion than did 8 simultaneous control donors, but there were
limited number of patients with malignancies, but there are      no symptoms suggestive of sickle crisis. Spontaneous
no data regarding its safety in healthy donors. Symptoms         splenic rupture is reported in 3 normal peripheral blood
among 1080 peripheral blood HSC donors surveyed by               HSC donors.18-20 In 2 cases the spleen was surgically re-
NMDP are shown in Table 2. Bone pain is the most com-            moved and disclosed extensive extramedullary hemato-
mon cytokine-associated symptom and likely results from          poiesis. Platzbecker et al performed ultrasound evaluations
altered bone metabolism, reflected by increased bone-de-         of spleen size before and after G-CSF mobilization in 91
rived alkaline phosphatase and decreased serum                   healthy donors.21 There were no adverse splenic events,
osteocalcin.12 It is typically diffuse but most prominent in     but increases in spleen length and width were routinely
the spine, hips or pelvis, and ribs and resolves promptly        seen. Growth factor may precipitate flares of autoimmune
when filgrastim is discontinued. Headache is also common.        disorders. Flares of rheumatoid arthritis and ankylosing
Pain is usually manageable with non-narcotic analgesics.         spondylitis are reported following therapy with filgrastim
Other symptoms include nausea and vomiting, myalgia,             or sargramostim in the non-donation setting. In patients
fatigue, insomnia and injection site reactions.                  with normal thyroid function, but pre-existing anti-thy-
     The apheresis procedure is also a source of adverse         roid antibodies, therapy with sargramostim has caused thy-
events. Securing peripheral venous access at antecubital         roid dysfunction. A variety of eye inflammatory responses
veins may produce bruising, hematoma or minor bleeding.          are reported in peripheral blood HSC donors, including
Anti-coagulation with acid-citrate-dextrose (ACD) solution       marginal keratitis, episcleritis and iritis during therapy with
may elicit symptoms of hypocalcemia—perioral numbness,
paresthesias and carpopedal spasms—requiring oral or pa-         Table 2. Symptoms reported by National Marrow Donor
rental calcium supplementation.                                  Program (NMDP) peripheral blood stem cell (PBSC)
     Important hematologic changes are expected with             donors, excluding reports of bone pain.
growth factors and apheresis. White blood cells, in particu-
lar neutrophils, increase dramatically. At daily filgrastim      Symptom          All Donors (N = 1080)
doses of 10 mg/kg or greater, the total white count may          Myalgia                     54%
reach 70–80 x 10 9/L. Although clinically significant            Headache                    52%
leukostasis is not reported, it is generally recommended         Malaise                     49%
that the filgrastim dose be reduced if the count exceeds 70-     Insomnia                    28%
75 x 109/L.13 Concomitant with leukocytosis, platelet counts     Nausea                      15%
decline, usually modestly. Peripheral leukocyte counts fall      Sweats                      14%
after apheresis. Mild neutropenia, lymphopenia and ane-
                                                                 Other flu-like Symptoms     12%
mia are common for a few weeks. Thrombocytopenia is the
                                                                 Anorexia                    11%
most significant finding post-apheresis. The platelet count
reproducibly declines between 20% and 30% with each              Fever                       6%
standard volume collection (i.e., 12 to 20 liters of processed   Chills                      6%
blood volume) and does not begin to recover until 3 to 4         Vomiting                    2%


472                                                                                        American Society of Hematology
filgrastim. Chest pain is occasionally encountered during      Assessing Risks to the Donor
peripheral blood donation and is generally non-cardiac in
origin, though one myocardial infarction has been reported.    Pre-donation history and physical
                                                               The medical history, which addresses risk to the donor, as
Death after HSC donation                                       opposed to the screening history described above, should
Death has occurred among normal marrow and peripheral          focus on matters relevant for the anticipated donation, in-
blood HSC donors. Nine deaths are documented, 6 in mar-        cluding psychological issues. For all donors, this includes
row donors and 3 in peripheral blood donors. Two of the        a review of known health problems, medications and aller-
reported deaths in marrow donors (both from cardiac arrest)    gies, and family history. Marrow donors should be ques-
actually occurred before the donation procedure could be       tioned about prior surgical procedures and types of anes-
done. The remaining 4 were from ventricular fibrillation,      thesia received. Marrow donors should also have a careful
respiratory arrest, myocardial infarction and pulmonary        review of systems directed toward neurological, respira-
embolism. The risk of death with marrow donation is esti-      tory, cardiovascular and musculoskeletal problems. Periph-
mated to be ~1 in 10,000. The 3 deaths after peripheral        eral blood donors should be questioned about prior whole
blood donation were from sickle crisis (described above),      blood or apheresis donations. The review of systems for
stroke and cardiac arrest. Given the relatively limited ex-    peripheral blood donors should include a careful cardio-
perience with allogeneic peripheral blood donations, the       vascular and neurological review as well as specific ques-
risk of death cannot currently be estimated but does not       tions about a history of venous access problems, autoim-
appear to be higher than with marrow donation.                 mune diseases, splenic disorders and hemoglobinopathies.
                                                               The donor’s physical examination should focus upon the
Infants and Children as Donors                                 neurological, respiratory and cardiovascular systems. Ad-
Children may safely donate marrow. They are probably more      ditionally, marrow donors need an assessment of the oral
likely than are adults to receive allogeneic blood transfu-    airway and an evaluation of access to the iliac crests. Among
sion, but serious complications among pediatric donors         obese donors, the ease of palpating the posterior, superior
are rare. Sanders et al reported on 23 marrow donors under     iliac spine varies widely. Donors with a history of musculo-
the age of 2.22 Harvested volumes were between 11.5 and        skeletal symptoms need a careful examination of the spine
19.3 mL/kg donor weight. One 14-month-old donor was            and lower extremities. Examination of peripheral blood HSC
discovered during predonation evaluation to have a stage       donors should additionally include evaluation of venous
1 neuroblastoma. The tumor was resected at the time of         access and an abdominal examination for splenomegaly.
marrow donation. Aside from this case, no serious compli-           The history and physical examination of donors is not
cations were encountered, but 22 of the 23 infants required    a comprehensive evaluation. Routine health care screen-
allogeneic blood. For children, recovery of autologous RBC     ing (e.g., fecal blood testing, Pap smears, mammograms) is
from the collected bone marrow product may be a useful         irrelevant for hematopoietic cell donations. However, the
strategy.23 Successful marrow collection from a 3.95 kg        evaluation for donation represents an opportunity to re-
donor is also reported.24 The collection volume represented    mind individuals of the importance of such screening. Do-
two-thirds of the donor’s total blood volume, essentially      nors who are delinquent with their general health care
necessitating exchange transfusion. Another case reported      should be advised to visit their personal physician or clinic.
collecting 335 mL of marrow from a 9.4 kg infant (total
blood volume 750 mL).25 In this instance, recovery of au-      Laboratory and procedural evaluations of donors
tologous red cells from the collected marrow avoided allo-     The laboratory evaluation of all donors should include the
geneic blood transfusion.                                      following: complete blood count with white blood cell
     In a survey of pediatric marrow transplant physicians,    differential, serum electrolytes, alanine aminotransferase
only 7 of 56 responders were unwilling to collect marrow       (ALT), bilirubin, creatinine or blood urea nitrogen (BUN),
from infant donors 0 to 6 months old.26 There was little       total serum protein and albumin.7 Peripheral blood HSC
agreement, however, on the management of large volume          donors should also have determinations of alkaline phos-
collections. Of 52 respondents, 6 would limit collections      phatase (AP) and lactate dehydrogenase (LDH). Additional
to 25% or less of the donor’s blood volume, whereas 24         evaluations, depending on findings of the history and physi-
placed the limit at 50% or higher. Twenty-two respondents      cal, may include urinalysis, chest X-ray, electrocardiogram
preferred to manage large volume collections in two stages.    and serum immunoglobulins.
     Children appear similar to adults with respect to their        Apparently normal HSC donors whose intended re-
response to filgrastim and collection by apheresis.27 How-     cipients suffer from inherited conditions, such as hemoglo-
ever, central venous access may be required more often for     binopathies or inborn errors of metabolism, may require
successful collection from children.                           specific testing to rule out carrier states that could affect
                                                               transplant outcome as well as donation complications.
                                                               Donors with sickle cell trait and thalassemia minor can
                                                               serve as donors in successful bone marrow transplants. As

Hematology 2005                                                                                                         473
discussed above, however, donors with S-beta thalassemia,       incumbent on the physician to recognize the potential for
SC or other complex sickle hemoglobinopathies should            conflict of interest, to seek expert ethical guidance when
not receive rhG-CSF. A pregnancy assessment must be per-        needed, and to ensure to the extent possible that the child
formed for female donors with childbearing potential. Preg-     donor is a willing and informed participant. Children who
nancy is considered an absolute contraindication to mar-        are able should provide assent for donation.
row donation for unrelated recipients but, in some circum-
stances, harvesting marrow from a pregnant relative may         Summary
be considered for patients with urgent clinical situations.     Allogeneic HSC donation is a safe procedure with very low
Safe and successful collection in the second trimester is       rates of serious adverse events. Nevertheless, all donors
reported. Pregnant women cannot be peripheral blood do-         must be carefully evaluated and fully informed prior to
nors as hematopoietic growth factor administration is con-      HSC donation by clinicians with good understanding of
traindicated.                                                   the potential physical and psychological complications
                                                                and factors that may increase risk. Donors must be able to
Psychological aspects of marrow donation                        provide informed consent without coercion or pressure.
The psychological condition of the donor should be as-          Special attention to the clinical and psychological needs
sessed. In particular, what are the donor’s motivations for     of pediatric donors is necessary.
considering the HSC donation? Is the donor acting out of a
genuine desire to help, or are there other motives involved;    References
perhaps an unrealistic expectation of reward or personal        1. Bakken R, van Walreaven A-M, Egeland T. Donor commit-
gain? Related donors may have different motivations from            ment and patient needs. Bone Marrow Transplant.
                                                                    2004;33:225-230.
unrelated donors and may be subject to increased emo-           2. Human cells, tissues, and cellular and tissue-based
tional and physical stress associated with donation.28,29 Oc-       products; donor screening and testing, and related labeling.
casionally donors may be subjected to coercion.30,31 Switzer        Fed Regist. 2005;70(100):29949-29952.
et al have reported that unrelated donors who feel they         3. Foundation for the Accreditation of Cellular Therapy.
                                                                    Standards for Hematopoietic Progenitor Cell Collection,
were pressured, either encouraged or discouraged about              Processing & Transplantation. (2nd ed.) Omaha: Foundation
donation, are less likely to have a positive donation expe-         for the Accreditation of Cellular Therapy (FACT); 2004.
rience.32 In an early report of unrelated donors, 9 of 20       4. National Marrow Donor Program. National Marrow Donor
reported being discouraged from donation by a relative or           Program Standards, 18th Edition. Minneapolis: National
                                                                    Marrow Donor Program; 2002.
a friend.33 To ensure unbiased evaluation and counseling        5. Strasser SI, McDonald GB. Hepatitis viruses and hemato-
of individuals intending to donate, whether it is to a re-          poietic cell transplantation: a guide to patient and donor
lated or an unrelated recipient, donor evaluation should be         management. Blood. 1999;93:1127-1136.
done by a clinician who is not involved in the care of the      6. Lau GKK, Liang R, Lee CK, et al. Clearance of persistent
                                                                    hepatitis B virus infection in Chinese bone marrow transplant
prospective recipient. Children who are being evaluated as          recipients whose donors were anti-hepatitis B core- and
potential marrow donors deserve special attention. Their            anti-hepatitis B surface antibody- positive. J Infect Dis.
fears and concerns may be complex and accompanied by                1998;178:1585-1591.
significant ambivalence.34,35                                   7. Lau GKK, Lie AKW, Kwong YL, et al. A case-controlled study
                                                                    on the use of HBsAg-positive donors for allogeneic
                                                                    hematopoietic cell transplantation. Blood. 2000;96:452-458.
Donor consent for HSC donation                                  8. Kollman C, Howe CWS, Anasetti C, et al. Donor characteris-
HSC donors must provide written consent prior to dona-              tics as risk factors in recipients after transplantation of bone
tion. Like a research subject, the HSC donor is a volunteer         marrow from unrelated donors: The effect of donor age.
                                                                    Blood. 2001;98:2043-2051.
who must receive full and complete information about his        9. Stroncek DF, Holland PV, Bartch G, et al. Experiences of the
or her donation. This means receiving a clear description           first 493 unrelated marrow donors in the National Marrow
of the procedure, its risks and potential alternatives. Do-         Donor Program. Blood. 1993;81:1940-1946.
nors must also have the opportunity to have questions sat-      10. Anderlini P, Przepiorka D, Seong D, et al. Clinical toxicity and
                                                                    laboratory effects of granulocyte-colony-stimulating factor
isfactorily addressed. Consent for children presents special        (filgrastim) mobilization and blood stem cell apheresis from
concerns. In general, children are only considered for HSC          normal donors, and analysis of charges for the procedures.
donation to a relative, usually a sibling. In most instances,       Transfusion. 1996;36:590-595.
parents are expected to consent for their children, which       11. Anderlini P, Donato M, Chan K-W, et al. Allogeneic blood
                                                                    progenitor cell collection in normal donors after mobilization
may create conflict of interest situations. A survey of pedi-       with filgrastim: The M.D. Anderson Cancer Center experi-
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