Evaluation of the hematopoietic cell transplantation donor

INTRODUCTION — 

Allogeneic hematopoietic cell transplantation (HCT) is an important and potentially curative treatment option for a wide variety of malignant and nonmalignant disorders. The graft, a mixture of very primitive hematopoietic stem cells and more mature committed progenitor cells, can be obtained from bone marrow, peripheral blood, or umbilical cord blood. Grafts may be from a related donor or from an unrelated donor.

Risks of donation of bone marrow or peripheral blood stem and progenitor cells are small, but it is critical that the donor evaluation determine that the collection procedure is safe for both the donor and the recipient. Advances in transplantation techniques have increased the age of transplant-eligible patients into the seventh and eighth decades, which increases the likelihood that potential sibling donors will be older and have comorbid conditions that could affect the health of either donor or recipient. Children and adolescents may also serve as donors for their relatives, but they require detailed plans for their safety.

This topic reviews the evaluation of a potential donor that has been identified as an appropriate match for an HCT recipient.

Related topics include:

●(See "Donor selection for hematopoietic cell transplantation".)

●(See "Collection and storage of umbilical cord blood for hematopoietic cell transplantation".)

●(See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation".)

●(See "HLA-haploidentical hematopoietic cell transplantation", section on 'Donor selection for haploidentical HCT'.)

GRAFT SOURCES — 

Bone marrow or mobilized peripheral blood stem and progenitor cells (PBSPCs) can be used as graft sources for allogeneic HCT.

The use of umbilical cord blood as a graft source is discussed separately. (See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation".)

Bone marrow is harvested by repeated needle aspirations of the posterior iliac crests. PBSPC grafts are collected by mobilizing hematopoietic stem and progenitor cells from the marrow into peripheral blood, where they can be collected via apheresis. Approximately 5 percent of the donor's stem cells are collected, but because stem and progenitor cells can self-renew, they replace themselves in weeks to months, leaving the donor with a full complement of hematopoietic stem cells. Details of bone marrow harvest and PBSPC mobilization are discussed separately. (See "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells".)

The age of the transplant recipient (ie, child versus adult) and/or the underlying condition (ie, malignant versus nonmalignant diseases) may influence the choice of graft source. Patient or donor preference may also influence the choice of graft source. Selection of a graft source for HCT is discussed separately. (See "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells", section on 'Preferred graft sources'.)

Both procedures are safe and are associated with moderate adverse effects (AEs) that require similar amounts of time to resolve. Bone marrow donors generally have localized pain at aspiration sites after donation, while PBSPC donors have discomfort in their bones before the harvest (caused by filgrastim used for mobilization).

●In a trial that randomly assigned donors to bone marrow donation versus PBSPC donation, bone marrow donors experienced more physical morbidity and negative impact on quality of life up to one month after donation, but most were willing to donate again [1]. Median time to return to full activity was four days for bone marrow donors and two days for PBSPC donors.

●A trial that randomly assigned graft source for unrelated patient-donor pairs reported that bone marrow donors experienced fewer concerns or confusion, more pain and limitation of social activities immediately after donation, more hospitalizations, a greater decrease in hemoglobin, and a greater sense of meaning from the donation [2-4]. PBSPC donors experienced more pain prior to donation due to bone pain from filgrastim.

●A Cochrane meta-analysis of six randomized trials of graft donation (807 donors) confirmed that both types of donors experienced pain and psychologic morbidity, but the timing of AEs differed [5]. There were trends toward more pain at the donation site, overall AEs, days of restricted activity, and hospitalization for bone marrow donors, while PBSPC donors experienced more pain prior to donation.

DONOR ASSESSMENT — 

Evaluation of a potential transplant donor includes physical examination, directed medical history, review of available medical records, infectious disease testing, and other studies, as clinically warranted.

Suitability and eligibility — Potential donors should be assessed for medical suitability and donor eligibility.

●Medical suitability – Medical suitability pertains to potential risks to the donor from the donation process and the possibility of transmitting an inherited or acquired condition.

Guidelines for donor health are available online from NMDP (National Marrow Donor Program).

Medical suitability may differ according to whether the donor is related or unrelated to the transplant recipient. Guidelines for unrelated donors are more restrictive than standard requirements for related donor transplantation. As an example, donors >60 years may be acceptable for related donor transplantation, but they are excluded as unrelated donors. Autoimmune diseases, diabetes-related complications, and other medical issues may be acceptable for a related donor, but such conditions are not considered acceptable for unrelated donors.

●Donor eligibility – Donor eligibility refers to assessment of risk for transmission of communicable diseases.

Risk of transmission of infectious or other diseases does not necessarily disqualify a donor. Prohibition of donors at risk of transmitting certain communicable diseases may be waived if there is an urgent medical need and the donor and recipient consent.

In the United States, unrelated donors are evaluated to comply with the guidelines and regulations from the US Food and Drug Administration (FDA), The Joint Commission (TJC), the Association for the Advancement of Blood and Biotherapies (AABB; formerly the American Association of Blood Banks), NMDP, and the Foundation for the Accreditation of Cellular Therapy (FACT).

Donor evaluation — Donor evaluation includes physical examination and a comprehensive health assessment to determine suitability and eligibility to serve as a transplant donor. (See 'Suitability and eligibility' above.)

A standardized questionnaire (Donor History Questionnaires [DHQ] and medication lists from the AABB website) is used as a checklist to avoid missing critical information related to donor eligibility; the questionnaire was developed by a task force to comply with United States regulatory agencies' requirements. (See 'Donor assessment' above.)

●History – Specific aspects of the history include:

•Screening for intravenous (IV) drug use, high-risk sexual activity, history of blood transfusions, pregnancies, tattoos, piercings, immunizations, and travel history.

•Travel history and residence to evaluate for exposure to malaria and other infections.

There is no specific testing for Creutzfeldt-Jakob disease (CJD). However, individuals with a history of CJD (or another transmissible spongiform encephalopathy), blood relatives of an individual with a familial prion disease, and potential donors who received cadaveric pituitary human growth hormone treatment or a cadaveric dura mater transplant are ineligible as donors in the United States. Further discussion of CJD is presented separately. (See "Blood donor screening: Medical history", section on 'Prion disorders'.)

•Autoimmune diseases – Conditions such as multiple sclerosis or ulcerative colitis may be transmitted to the recipient.

•Hemoglobinopathies – Neither sickle cell trait nor thalassemia minor is a risk for the recipient, but hemoglobin electrophoresis may be performed to evaluate these conditions in a potential donor.

●Laboratory studies

•Hematology – Complete blood count with white cell differential.

•Chemistries – Comprehensive metabolic panel, including electrolytes and liver and kidney function tests.

•Infectious disease – A standard panel of infectious disease markers includes human immunodeficiency virus (HIV) serology and nucleic acid testing, human T-lymphotropic virus (HTLV)-1 and HTLV-2 serology, West Nile virus nucleic acid testing, hepatitis B and C serology and nucleic acid testing. Testing for syphilis, West Nile Virus, and cytomegalovirus (CMV) serology are required, mirroring the FDA requirements for normal blood donors (table 1).

-Donors with confirmed HIV infection are ineligible to donate.

-Donors with antibodies to hepatitis B or C are considered ineligible, but they can donate if the need is urgent and the donor and recipient provide consent. If nucleic acid testing demonstrates viremia, donors may be acceptable for related donors, depending on the serology of the recipient and the ability to receive effective antiviral therapy. Viremic donors are not acceptable donors for unrelated recipients.

-If the donor has had high-risk behavior associated with HIV infection, human herpesvirus 8 (HHV8) testing should be considered. (See "Acute and early HIV infection: Pathogenesis and epidemiology", section on 'Risk factors'.)

•Fertility – Serum pregnancy testing is required for all female donors <55 years unless the donor is postmenopausal or is surgically infertile.

A pregnant individual may serve as a donor for a related recipient if the transplantation is considered urgent. Bone marrow donation in the second trimester of pregnancy is thought to be safe, but pregnant donors should not receive filgrastim because the risk to the fetus is uncertain.

Pregnant donors are disqualified from donating to unrelated recipients until fully recovered after delivery (usually six weeks postpartum).

●Other clinical testing – Chest radiography, electrocardiogram (ECG), urinalysis, or other testing is performed, as clinically warranted. Examples include ECG for an individual with a history of coronary disease, arrhythmias, or heavy smoking.

Occasionally, a donor may be found to have abnormal hematologic parameters that warrant bone marrow examination to determine eligibility. Such abnormalities are not absolute contraindications to eligibility, but they must be assessed in the context of the indication for transplantation, donor availability, and risk to the recipient.

Psychologic effects — Psychologic testing has determined that donation is considered altruistic and desirable for most donors. Both related donors and unrelated donors feel a satisfaction and pride in their role, but there are potential risks.

Some family member donors feel compelled to donate by pressure from relatives, and some may feel neglected because the relatives' energy and attention are directed towards the patient. The satisfaction and pride associated with donation may be tempered by guilt and/or a sense of personal responsibility complicating their grief if the recipient relapses or dies [6-10].

INFORMED CONSENT — 

All donors must be fully informed of the risks and benefits of donation and sign consent forms indicating that they understand the risks and have been informed of alternative procedures. Donors can refuse either bone marrow donation, peripheral blood stem and progenitor cell donation, or both procedures.

Donor evaluators are separate from the transplantation team to avoid a conflict of interest and potential coercion.

Subtle coercion on the part of family members is difficult to prevent. This requires a private evaluation with the donor and provision of a safe mechanism to refuse donation. For donors <18 years old, private evaluation may not be advised or possible; in such circumstances, evaluation with a pediatric social worker or other professional may be useful and required in some instances. Other aspects of grant donation by minors are discussed below. (See 'Children as donors' below.)

BONE MARROW DONATION — 

Bone marrow collection requires general or regional anesthesia, which subjects the donor to anesthesia-related risks.

Obese donors may have an increased risk of pain, hematoma formation, venous thromboembolism, and anesthesia-related risks. Donors with body mass index (BMI) >40 are deferred from bone marrow donation.

Preoperative assessment — Preoperative evaluation should include:

●Assessment of underlying health issues, such as coronary artery disease, diabetes, sleep apnea, or hypertension, to evaluate risk and provide appropriate management during and after the collection. (See "Evaluation of cardiac risk prior to noncardiac surgery" and "Preoperative evaluation for noncardiac surgery in adults".)

●Evaluation of the posterior iliac crests (figure 1) to determine their accessibility, especially in obese donors. Donors with a history of low back problems should have an assessment of this area to be sure the marrow collection does not exacerbate a pre-existing condition. (See "Evaluation of low back pain in adults", section on 'Physical examination'.)

●Airway assessment to predict the degree of difficulty with mask ventilation and endotracheal intubation using standard devices. (See "Airway management for general anesthesia in adults", section on 'Airway assessment'.)

Donors should not ingest potential bone marrow suppressive agents (eg, alcohol, clopidogrel) for ≥14 days before donation, and they should avoid nonsteroidal anti-inflammatory medications (eg, aspirin, ibuprofen, naproxen sodium) for 24 hours prior to donation.

Iron supplements should be considered in donors with hemoglobin level <13 g/dL (especially menstruating females) for one month prior to and after marrow donation. (See "Treatment of iron deficiency anemia in adults", section on 'Oral iron'.)

Bone marrow collection — Bone marrow collection is performed in the operating room under sterile conditions.

Multiple aspirates of the posterior iliac crests are performed using a large bore needle under general or regional anesthesia. Additional bone marrow can be obtained from the anterior iliac crest, but this site is rarely used because the amounts available are relatively limited.

The volume of collection is determined by the size of the recipient and may also be influenced by the nature of subsequent processing prior to infusion. For grafts that will not be T cell-depleted, this typically amounts to 10 mL/kg of recipient weight, but for T cell-depletion protocols, 15 to 20 mL/kg of recipient weight may be needed. A maximum of 1500 mL is typically collected, but that is dependent on the donor's size. Some centers target collection of ≥2 x 10⁸ nucleated cells or ≥2 x 10⁶ CD34+ cells/kg recipient body weight.

Donors should refrain from heavy lifting and high-impact exercises (eg, jogging, aerobic dancing) for approximately six weeks after bone marrow donation to allow the iliac crest to heal. Because of the heightened risk of bleeding, aspirin should be avoided for ≥14 days, and other nonsteroidal anti-inflammatory drugs should be avoided for 48 hours after donation if there is no bleeding.

Complications — Bone marrow harvest frequently causes mild to moderate back or hip pain, fatigue, and transient changes in peripheral blood cell counts. Donors typically require iron replacement and analgesics after the collection. Serious complications of bone marrow harvest are extremely rare and involve mechanical injury, complications of anesthesia, infection, or bleeding [11].

NMDP (National Marrow Donor Program) reported that among 9245 bone marrow harvests from volunteer donors, 1.35 percent experienced a serious medical complication [10]. Complications thought to be directly related to the procedure resulted in mechanical injury to tissue, bone, or nerve (69 individuals); complications of anesthesia (45); infection (1); and a grand mal seizure (1). Median time to recovery for those donors who experienced a serious medical complication was 10 months, but 67 experienced prolonged recovery time. Subsequent studies have reported a similarly low risk of complications, with faster recovery in peripheral blood stem cell donors than in bone marrow donors [2,11]. (See 'Peripheral blood progenitor cell collection' below.)

NMDP also reported less serious but common symptoms in 2505 bone marrow harvests [10]:

●Symptoms

•Pain was the most common acute symptom. On day 2 after donation, patients reported back and/or hip pain (82 percent), throat pain (33 percent), or headache (17 percent). Pain was generally mild (grade 1), and it resolved in >80 percent of donors by one month; by one year, the percent of patients with pain (<10 percent) was like that seen prior to the procedure.

•Fatigue was the second most common symptom. On day 2, mild to moderate fatigue was reported in 59 percent of donors, but it resolved in 95 percent by one month after donation.

•Other less common side effects were site reaction, insomnia, nausea, dizziness, and anorexia.

●Blood counts

•Anemia – Most donors experienced approximately 3 g/dL decrease in hemoglobin (Hb) immediately after donation; Hb remained slightly decreased one month postdonation, but it returned to baseline by one year.

Some experts encourage autologous blood donation prior to bone marrow harvest, but there is controversy about its value [12].

•Others – There was an immediate slight increase in white blood cell count (median 9.7 x 10⁹/L) and decrease in platelet count (median 214 x 10⁹/L) that returned to baseline by one month postdonation.

Median time to full recovery of blood counts was approximately three weeks. Full recovery was reported by 70 and 95 percent of bone marrow donors by one and three months after donation, respectively.

Bone marrow harvest is safe for pediatric bone marrow donors [13-15]. As an example, no serious complications were reported among 313 pediatric bone marrow donors [15]. However, the risk of requiring a red blood cell transfusion following bone marrow harvest was highest among patients <4 years and for those requiring a bone marrow harvest volume >20 mL/kg. Such donors may be considered for autologous blood donation prior to bone marrow harvest, and harvest volumes should not exceed 20 mL/kg. (See 'Child bone marrow donors' below.)

PERIPHERAL BLOOD PROGENITOR CELL COLLECTION

Procedure — Hematopoietic stem and progenitor cells are stimulated to enter the circulation ("mobilized") to provide an adequate quantity for harvesting from peripheral blood by apheresis.

Briefly, peripheral blood stem and progenitor cell (PBSPC) harvesting involves the following steps:

●Mobilization – Administration of granulocyte colony-stimulating factor (G-CSF, filgrastim) over four to six consecutive days is usually adequate for mobilizing sufficient PBSPCs.

If G-CSF does not yield adequate PBSPC mobilization, plerixafor or motixafortide can be administered to enhance PBSPC collection. Details of PBSPC mobilization are presented separately. (See "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells", section on 'Peripheral blood grafts'.)

●Apheresis – The apheresis procedure typically processes two to four blood volumes and takes three to six hours, depending on donor size, donor stem/progenitor cell count, and the quantity needed for the recipient. Approximately two-thirds of donors provide adequate progenitor/stem cells in a single session; the remainder require a second or, rarely, a third session [16,17].

●Venous access – Many donors undergo the apheresis procedure using peripheral intravenous access. Smaller donors and others may require the placement of a temporary central apheresis catheter that, if needed, is typically done under sedation. (See 'Apheresis-related' below.)

Further details of cell doses and PBSPC mobilization, graft collection, and infusion are presented separately. (See "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells", section on 'Peripheral blood grafts'.)

Adverse effects — The complication rate for PBSPC donation is low, but there are potential risks for the donor related to the administration of filgrastim and to the apheresis procedure.

Cytokine-related — In healthy donors, filgrastim is associated with a very low rate of severe complications (eg, case reports of splenic rupture). However, nearly all donors experience mild to moderate generalized musculoskeletal pain, and some donors experience flu-like symptoms. Filgrastim should not be administered to pregnant donors because potential risks to the fetus have not been determined.

Adverse effects (AEs) associated with G-CSF in this setting include:

●Pain – Most donors experience mild to moderate (grade 1 or 2) generalized musculoskeletal pain within 24 hours of G-CSF administration. This pain peaks around day 5 and usually returns to baseline within one week.

Some donors require acetaminophen or narcotic analgesics for several days prior to donation. Daily loratadine (starting three days prior to first injection of G-CSF) may minimize bone/muscle/joint pain and body aches; the dose can be increased to twice daily and continued or stopped after the last injection, as guided by symptoms. Aspirin should be avoided for ≥14 days before and after donation due to the heightened risk of bleeding during the procedure and because thrombocytopenia may follow PBSPC donation. Nonsteroidal anti-inflammatory drugs can be used if acetaminophen and loratadine are insufficient.

AEs following G-CSF administration to donors with sickle cell trait were similar to those in the general population [18]. (See "Sickle cell trait", section on 'Hematopoietic stem cell donation'.)

●Leukocytosis – The total white blood cell (WBC) count rises during filgrastim administration, often achieving levels of 50 to 80 x 10⁹/L, but leukocytosis, per se, does not entail any direct risk. Some donor centers limit the use of filgrastim to keep the total WBC within local guidelines.

An NMDP (National Marrow Donor Program) study of 6768 PBSPC donors reported mean WBC count 40 x 10⁹/L on day 5 (just before apheresis); 20 percent of donors had >50 x 10⁹ WBC/L and one donor had >100 x 10⁹ WBC/L [17].

●Spleen size – Spleen volume increased by ultrasound in a prospective study in 309 donors who received filgrastim, but there were no splenic ruptures [19]. Median spleen volume increased nearly 1.5-fold on the first day of apheresis, but it declined to near pretreatment levels seven days after last apheresis.

●Hematologic malignancies – There is no evidence of increased hematologic malignancies in donors.

A study of 51,024 transplants from the European Group for Blood and Marrow Transplantation (EBMT) reported 20 hematologic malignancies among donors (12 among PBSPC donors and 8 in bone marrow donors) [16]. The observed incidence rate of hematologic malignancies did not exceed the expected incidence in an age- and sex-adjusted general population. Other reports also showed no increased incidence of leukemia in PBSPC donors [16,20-22].

A longitudinal investigation found no evidence that older age (ie, >60 years) was associated with worse donation-related outcomes or health-related quality of life (HRQoL) [23].

Apheresis-related — Apheresis is a well-tolerated procedure. Peripheral venous access is adequate for most apheresis collections, but some donors may require a temporary central venous catheter.

The most common apheresis-related AE was numbness or tingling that was transient (33 to 45 percent), persistent and moderate (2 to 8 percent), or severe (<1 percent); tetany occurred in <1 percent [17]. Other AEs included nausea and/or vomiting (<2 percent) and mild to moderate local intravenous site infections (<1 percent).

Occasional donors with small veins require a temporary central venous catheter to enable an adequate collection. Central line complications include pain on insertion, pneumothorax, hemorrhage, or infection. Management of donors with coronary artery disease, hypertension, or diabetes requires special attention on the part of the apheresis staff since the changes in blood volume and administration of glucose-containing fluids can result in angina, hypotension, and hyperglycemia in susceptible donors. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Complications", section on 'Evaluation for suspected complications'.)

●Central venous access was required for 21 percent of females and in 5 percent of males in a report from NMDP; hospitalization was required in <3 percent of donors [17]. In our experience, this rate of central venous catheter insertion is high, and most can be avoided by well-trained personnel.

●There were four fatalities (incidence 0.98 per 10,000 donations) and 25 severe AEs (10.76 per 10,000 donations) among 23,254 PBSPC donations in a report from the EBMT [17].

A prospective longitudinal investigation found no evidence that older age (ie, >60 years) was associated with worse donation-related outcomes or HRQoL [23].

Blood counts — Thrombocytopenia and anemia may be seen for days or weeks after apheresis, but they are generally not clinically significant, and most cases resolve within one month of donation. Leukocytosis with G-CSF administration is described above. (See 'Cytokine-related' above.)

Decreases in blood counts are generally mild and transient. In an NMDP study, no donor had platelets <20 x 10⁹/L, and no platelet transfusions were required [17]. Platelets decreased to <100 x 10⁹/L in 26 percent of donors after a single apheresis session and to <50 x 10⁹/L in <1 percent. After two days of apheresis, platelets were <100 x 10⁹/L in 50 percent and <50 x 10⁹/L in 1 percent. Hemoglobin was <8 g/dL in 0.1 percent of males and in 0.2 percent of females. More than one-half of donors reported resolution of toxicities one week after collection. Complete recovery was experienced by >90 percent of donors at one month and by 100 percent at six months.

CHILDREN AS DONORS — 

Children and adolescents <18 years are not allowed to serve as donors for unrelated transplant recipients, but they may be asked to donate for a relative, most often a sibling.

Compared with unrelated adult donors, grafts collected from a minor sibling are associated with fewer transplant-related complications and greater overall survival (OS) for the recipient [4]. Most pediatric transplant clinicians felt that it is acceptable to expose minor siblings to the risks of donation when it offers the relative the potential of benefit [24].

Guidelines for minor donors — The American Academy of Pediatrics (AAP) released a policy statement that outlined five conditions that should be met for a minor to serve as a donor [25]:

●No medically equivalent histocompatible adult relative is willing and able to donate.

●A strong personal and positive relationship exists between the donor and recipient.

●There is some likelihood that the recipient will benefit from transplantation.

●The clinical, emotional, and psychosocial risks to the donor must be minimized and reasonable in relation to the benefits expected to accrue to the donor and the recipient.

●Parental permission and donor assent (when developmentally appropriate) must be obtained.

The AAP also recommended that all potential minor donors should have a donor advocate or a similar individual, who is educated in pediatric development and independent from the team, directly responsible for the recipient's care.

Selection of a minor donor — The most important factor when selecting a minor donor is the degree of immunocompatibility. There is no direct medical benefit to minor donors, and any potential benefits are expected to be psychosocial.

If the recipient is undergoing transplantation for an inherited condition, the potential donor must be adequately screened for the same disease or for genetic carrier status. In some situations, it is acceptable to use a donor who is a genetic carrier of the condition for which the transplant is being performed.

There are no widely accepted guidelines for choosing a donor among equally immunocompatible siblings who are unaffected by the recipient's underlying disease [25]. The AAP favors the potential donor who is closest to the age of consent and avoidance of donors who are developmentally unable to provide assent, when possible.

Selection of a donor for allogeneic HCT is discussed in more detail separately. (See "Donor selection for hematopoietic cell transplantation".)

Child bone marrow donors — Bone marrow is the most common graft source in pediatric transplantation, and the risks to minor bone marrow donors are similar to those experienced by adult donors. (See 'Complications' above.)

●A multicenter prospective study of 294 pediatric donors reported that 71 percent of children reported pain and 59 percent reported other symptoms in the peri-donation period, which declined to 14 and 12 percent, respectively, one month after donation [26]. Higher levels of pain were experienced by females and older donors (13 to 17 years).

●A study of 313 minor bone marrow donors found that 50 percent required medication to control pain [15]. The most frequent anesthesia-related adverse effects (AEs) were vomiting (12 percent), sore throat (7 percent), hypotension (6 percent), tachycardia (4 percent), and bradycardia (0.6 percent).

Child peripheral blood stem and progenitor cell donors — Peripheral blood stem and progenitor cell (PBSPC) donation presents distinct challenges to minor donors.

●AEs related to granulocyte colony-stimulating factor (G-CSF) are similar to those experienced by adult donors, though pain is less frequently reported by minor donors [15,25].

●Most donors <12 years require central venous access, with the attendant risks of conscious sedation or general anesthesia [27]. Serious complications of central line placement in donors were reported in <2 percent of minor donors [4,15].

●Discordance between weight of the donor and recipient may increase the number of days needed for collection. More than one-half of the children required more than one day of collection in a study of 140 minor PBSPC donors [15].

●Younger, smaller donors are at greater risk for exposure to blood products due to the need to prime the apheresis circuit with blood products in children who weigh <20 kg [27].

There is a broad range of response to donation in minors, but there are few studies of the psychosocial effects of donation. Donors may be impacted by clinical, family, and psychosocial variables, but both donor and nondonor siblings experience stress related to their sibling's transplant [28-30].

A longitudinal study of the health-related quality of life (HRQoL) of pediatric sibling donors found that approximately 20 percent of child donors for a sibling reported poor HRQoL [31]. Younger donors experienced more prominent impacts on HRQoL predonation, four weeks after donation, and one year after donation; the minor's report of donor HRQoL was generally higher than that from the parents [31].

SECOND DONATIONS — 

A marrow or peripheral blood stem and progenitor cell (PBSPC) donor may be contacted again if the graft is rejected, the patient relapses, or there is an infection that requires additional immune cells.

Relapse — Recruiting the donor for another blood product involves the timing and tempo of the relapse and the clinical condition of the recipient.

●Donor lymphocyte infusion – Donor lymphocyte infusion (DLI; donation of peripheral blood lymphocytes from the original donor) can generate a remission via the graft-versus-leukemia effect. DLI does not require filgrastim administration, so it is generally easier than PBSPC donation. DLI can also provide immunologically competent cells to a patient who cannot clear an opportunistic infection [32-34]. (See "Immunotherapy for the prevention and treatment of relapse following allogeneic hematopoietic cell transplantation".)

●Second donation – If donor lymphocyte infusion is considered inadequate and a second transplantation is planned, either PBSPC or bone marrow may be requested. If the initial product was marrow, transplant clinicians typically request a PBSPC graft for the second donation, in case the iliac crest has not completely recovered hematopoiesis.

Graft failure — Graft rejection is an uncommon complication of allogeneic HCT.

The incidence of graft rejection varies with the type of transplantation. Graft rejection is seen in 0.01 to 10 or 15 percent of cases and is influenced by the type of transplantation, human leukocyte antigen (HLA) compatibility, intensity of the conditioning regimen, and other factors.

Graft rejection can occur early with no evidence of hematologic recovery in the first month after transplantation, or it can occur months later.

Graft insufficiency or graft exhaustion describes situations in which it appears that too few stem/progenitor cells were administered with the initial transplantation. Depending on the timing, clinical circumstances, and the cause of graft failure, the transplant team may request either marrow or PBSPC for a second procedure.

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Donating bone marrow or blood stem cells (The Basics)")

SUMMARY

●Description – Bone marrow or mobilized peripheral blood stem and progenitor cells (PBSPCs) can be used as graft sources for allogeneic hematopoietic cell transplantation (HCT). Grafts can be obtained from related (eg, sibling) or unrelated donors. (See 'Graft sources' above.)

●Graft selection – The choice of graft source may be influenced by the age of the transplant recipient (ie, child versus adult) and/or the underlying condition (ie, malignant versus nonmalignant diseases), as discussed separately. (See "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells", section on 'Preferred graft sources'.)

Umbilical cord blood as a graft source is discussed separately. (See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation".)

●Donor assessment – The donor must be evaluated for (see 'Donor assessment' above):

•Medical suitability – Risks to the donor from the donation process and the possibility of transmitting an inherited or acquired condition.

•Donor eligibility – Assessment of risk for transmission of communicable diseases.

●Evaluation – Risks for transmission of communicable diseases are evaluated by physical examination and comprehensive health assessment. A standardized questionnaire (Donor History Questionnaires [DHQ] and medication lists from the Association for the Advancement of Blood and Biotherapies [AABB] website) can help to avoid missing critical information. (See 'Donor evaluation' above.)

●Psychologic effects – Donation for HCT is an altruistic and rewarding act of generosity. However, some related donors may feel coerced to donate by relatives, neglected from attention directed towards the patient, and/or guilt or personal responsibility if the recipient relapses or dies. (See 'Psychologic effects' above.)

●Informed consent – Donors must be informed of risks and benefits of donation and sign appropriate consent forms. Evaluators of donors are separate from the transplantation team to avoid conflicts of interest and/or coercion. (See 'Informed consent' above.)

●Bone marrow donation

•Assessment – The bone marrow donor is assessed for comorbid conditions and the status of the iliac crests and airway. (See 'Preoperative assessment' above.)

•Collection – Bone marrow is collected in an operating room under general or regional anesthesia by multiple aspirates from the posterior iliac crests using a large bore needle. (See 'Bone marrow collection' above.)

•Complications – Pain, fatigue, and transient changes in blood counts are common, but major risks primarily relate to anesthesia. (See 'Complications' above.)

●PBSPC donation

•Procedure – Filgrastim (granulocyte colony-stimulating factor [G-CSF]) is given for five days before collection to mobilize PBSPCs, and most specimens are harvested by apheresis in a single procedure lasting three to six hours. (See 'Procedure' above.)

•Complications – Pain related to filgrastim, transient declines in blood counts, and need for central venous access in some small or younger donors. (See 'Adverse effects' above.)

●Minors – Children <18 years can safely donate bone marrow or PBSPCs, but only for a related recipient. Guidelines by the American Academy of Pediatrics for graft donation by minors are presented above. (See 'Children as donors' above.)

●Second donations – The donor may later be asked to provide a donor lymphocyte infusion for treatment of disease relapse, or a second graft may be used for graft failure. (See 'Second donations' above.)