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Evaluation of the hematopoietic cell transplantation donor

Evaluation of the hematopoietic cell transplantation donor
Literature review current through: Sep 2023.
This topic last updated: Jan 14, 2022.

INTRODUCTION — Allogeneic hematopoietic cell transplantation is an important and potentially curative treatment option for a wide variety of malignant and nonmalignant disorders. The multipotent hematopoietic stem cells required for this procedure are usually obtained from the bone marrow, peripheral blood, or umbilical cord blood of a related or unrelated donor. The hematopoietic products used for transplantation have a mixture of very primitive stem cells and more mature committed progenitor cells; these two levels of maturation of hematopoietic cells cannot be distinguished morphologically.

The term "hematopoietic cell transplantation" (HCT) will be used throughout this review as a general term to cover transplantation of hematopoietic progenitor/stem cells from any source (eg, bone marrow, peripheral blood, umbilical cord blood). Otherwise, the source of such cells will be specified (eg, autologous peripheral blood stem/progenitor cell transplantation). The peripheral blood hematopoietic product will be termed PBPC (peripheral blood progenitor cells) recognizing that stem cells must be present for long-term hematopoietic engraftment. (See "Sources of hematopoietic stem cells".)

Given there is the potential for harm, it is critical that the donor evaluation determine both that the collection procedure is safe for the donor and the recipient. This is particularly important as advances in transplantation have resulted in an increase in allowable patient age into the seventh decade, which increases the likelihood that potential sibling donors will be older and have co-morbidities that could affect the health of either the donor or the recipient. Infants may also serve as donors for their siblings, but require detailed plans for their safety.

This topic will review the evaluation of a potential donor that has been identified as an appropriate match for a transplant recipient. The general issues involved in donor selection for allogeneic HCT and the use of umbilical cord blood for transplantation are discussed separately.

(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'.)

CANDIDACY FOR DONATION

Donor guidelines — In the United States, unrelated donors are evaluated to comply with 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), the National Marrow Donor Program (NMDP), and the Foundation for the Accreditation of Cellular Therapy (FACT) guidelines and regulations. Guidelines for donor health are available on the BeTheMatch website. This set of guidelines is somewhat more restrictive than standard requirements for related donor transplantation. For instance, donors older than 60 years may be acceptable for related donor transplantation but are excluded by the NMDP. At times, if the risk is considered acceptable, related donors with autoimmune diseases, diabetes related complications, and other medical issues may be used within families but are excluded for unrelated donors.

Donors are assessed for medical suitability and donor eligibility. Medical suitability pertains specifically to assessing potential risks to the donor from the donation process and the possibility of transmitting an inherited or acquired condition. Donor eligibility refers specifically to an FDA required assessment for the increased risk for transmission of relevant communicable diseases. The evaluation for medical suitability and donor eligibility includes a physical examination, directed medical history, a review of available medical records, infectious disease testing, and additional testing that may be warranted by virtue of any underlying pre-existent conditions. Risk of transmission of infectious or other diseases does not necessarily disqualify a donor; however, the recipient must be informed of the potential risk. The stringent prohibition of donors at risk of transmitting certain communicable diseases may be waived if use of the donor is determined to be in the best interest of the patient.

Assessing for risks to the recipient — The donor evaluation process includes a physical exam and comprehensive health assessment including screening for intravenous (IV) drug use, history of blood transfusions, pregnancies, abortions, tattoos, immunizations, and travel history. A standardized questionnaire (Donor History Questionnaires [DHQ] and medications lists from the AABB website) is used as a checklist to avoid missing critical information related to donor eligibility [1]. This questionnaire was developed by an AABB task force to comply with requirements of the FDA, FACT, and the NMDP. We also perform the following tests:

Complete blood count with white cell differential, chemistries with liver and renal function and electrolytes are included in the screening of all donors.

A standard panel of infectious disease markers includes HIV, HTLV-1 and HTLV-II, West Nile virus, hepatitis A and B serologies, as well as hepatitis B and C viral load. Chagas disease, syphilis, and CMV serology are required, mirroring the FDA requirements for normal blood donors (table 1).

Donors who have antibodies to hepatitis B or C are eligible to donate. If polymerase chain reaction (PCR) testing demonstrates viremia, donors may be acceptable for family member donation 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, HHV8 testing should be conducted. Donors with confirmed HIV are unable to donate. (See "Acute and early HIV infection: Pathogenesis and epidemiology", section on 'Risk factors'.)

Serum pregnancy testing is required for all female donors less than 55 years unless the donor is postmenopausal or is surgically infertile. Marrow donation in the second trimester is thought to be safe; however, it is limited to donation for related donors if the transplantation is considered to be urgent. Pregnant donors cannot receive filgrastim, because the risk to the fetus has not been determined. Pregnant donors are disqualified from donating to unrelated recipients until after delivery.

Testing with chest radiography, urinalysis, or electrocardiogram (ECG) is performed if there are underlying problems that may warrant evaluation, for instance a history of coronary disease, arrhythmias, or heavy smoking.

Hemoglobin electrophoresis may be performed in potential donors who have relatives with a hemoglobinopathy (eg, thalassemia, sickle cell) or if there is suspicion that the donor is a carrier. Neither sickle cell trait nor thalassemia minor is a risk for the recipient.

We inquire about travel history and residence to assess for exposure to malaria, Zika virus, and other infections. There is no specific testing for vCJD (variant Creutzfeldt-Jakob disease), but donors meeting residence requirements in Europe are still considered ineligible (although rarely disqualified). (See "Blood donor screening: Medical history", section on 'CJD and vCJD deferral criteria'.)

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

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

Informed consent — All donors must be fully informed of the risks and benefits of donation and sign appropriate consent forms indicating that they understand the risks and that they have been informed of alternative procedures. In order to avoid a conflict of interest and potential coercion, the donor evaluators are separate from the transplantation team. More subtle coercion on the part of family members is difficult to prevent and requires a private evaluation with the donor and the provision of a safe mechanism to refuse donation. For donors <18 years old, private evaluation may not be advised or possible; in those instances, evaluation with a pediatric social worker or other professional may be useful. The transplant clinicians may request either peripheral blood progenitor cells or bone marrow, and the donor must be aware they can refuse either one or both of the procedures.

Additional information regarding informed decision making and effective communication is presented separately. (See "Informed procedural consent".)

Assessing for risks to the donor from the collection process — Hematopoietic stem/progenitor cells can be obtained from the donor either via direct needle aspiration of the posterior iliac crests (bone marrow donation) or by mobilizing cells from the marrow into the blood where they can be collected via leukapheresis (peripheral blood progenitor cell [PBPC] donation). Approximately 5 percent of the donor's stem cells are collected. These cells have the capacity for self-renewal and replace themselves in weeks to months, leaving the donor with a full complement of hematopoietic stem cells. There is often a period of discomfort that either precedes donation, as in the case of PBPC, or follows donation if marrow is collected. In both cases, donors return to fully normal performance over the course of days to weeks after the donation.

Details regarding bone marrow harvest and PBPC mobilization are discussed separately. (See "Sources of hematopoietic stem cells".)

Psychological effects — Psychological testing has determined that donation is considered altruistic and desirable for most donors; however, some family member donors feel compelled to donate by pressure from relatives. They at times feel neglected since the family's energy is directed towards the patient. But both related and unrelated donors feel a satisfaction and pride in their role, although it may be tempered by guilt and a particular sense of personal responsibility complicating their grief if the recipient relapses or dies [2-6].

Bone marrow donation — Bone marrow donation is performed under general or regional anesthesia and is therefore subject to risks associated with these forms of anesthesia. Obese donors may have an increased risk of pain, hematoma formation, venous thromboembolism, and anesthesia risk.

Preoperative assessment — Preoperative evaluation should specifically include:

An assessment 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'.)

An assessment of underlying health issues such as coronary artery disease, diabetes, sleep apnea, or hypertension to evaluate the risk and provide appropriate management during and after the collection. (See "Preoperative medical evaluation of the healthy adult patient" and "Evaluation of cardiac risk prior to noncardiac surgery".)

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

All donors are informed not to ingest potential bone marrow suppressive agents, such as alcohol or clopidogrel, for at least 14 days before donation and to avoid non-steroidal anti-inflammatory medications such as ibuprofen or naproxen sodium for 24 hours prior to donation. Any donor with a hemoglobin of <13 g/dL should take iron supplements for one month prior to and after marrow donation, if feasible. (See "Treatment of iron deficiency anemia in adults", section on 'Oral iron'.)

In the past, autologous blood was sometimes collected prior to donation in case transfusion was needed, but several studies have demonstrated that transfusion is rarely required [7-9]. Other reasons for avoiding autologous blood donation are discussed separately. (See "Surgical blood conservation: Preoperative autologous blood donation", section on 'Reasons for declining use'.)

Bone marrow collection — Bone marrow collection is performed in the operating room under sterile conditions. Multiple aspirates of the posterior iliac crests are performed under general or regional anesthesia using a large bore needle. Additional bone marrow can be obtained from the anterior iliac crest; however, the amounts available are relatively limited and this site is rarely used.

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 non T cell depleted transplants, this typically amounts to 10 mL/kg of recipient weight. For T cell depletion protocols, 15 to 20 mL/kg of recipient weight may be utilized. A maximum of 1500 mL is typically collected, but that is dependent on the donor's size.

Donors are asked to refrain from heavy lifting and high impact exercises (eg, jogging, aerobic dancing) for approximately six weeks to allow the iliac crest to heal. The use of aspirin and nonsteroidal anti-inflammatory drugs is avoided because of the heightened risk of bleeding.

Complications — Bone marrow harvest is frequently complicated by mild to moderate back or hip pain, fatigue, and transient changes in peripheral blood cell counts. Donors typically require iron replacement and analgesia after the collection. Serious complications of bone marrow harvest are extremely rare and involve mechanical injury, complications of anesthesia, infection, and bleeding [10].

The National Marrow Donor Program (NMDP) has kept careful records of the volunteer donors who have undergone bone marrow collection. In the first 9245 harvests, 125 donors (1.35 percent) experienced a serious medical complication [6]. Of these, complications thought to be directly related to the procedure resulted in mechanical injury to tissue, bone, or nerve (n = 69), anesthetic complications (n = 45), infection (n = 1), and a grand mal seizure (n = 1). The median time to recovery following donation for this population that experienced a serious medical complication was 10 months, but 67 experienced prolonged recovery time. Subsequent studies have shown similarly low risks of complications, with faster recovery in peripheral blood stem cell donors than in bone marrow donors [10,11]. (See 'Peripheral blood progenitor cell (PBPC) collection' below.)

Data regarding less serious, but common, symptoms associated with donation were collected by the NMDP regarding 2505 harvests with the following results [6]:

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). The pain was mild (grade 1) in the majority and resolved in over 80 percent by one month, and by one year the percent of patients with pain (<10 percent) was similar to 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 resolved by one month in the majority (95 percent).

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

Immediately after donation, most donors experienced an approximately 3 g/dL decrease in hemoglobin. Hemoglobin remained slightly decreased at one month post-donation, but returned to baseline by one year. In addition, there was an immediate slight increase in white blood cell count (median 9.7 x 109/L, interquartile range 7.6 to 12.7) and decrease in platelet count (median 214 x 109/L, interquartile range 179 to 252) that returned to baseline by one month post-donation. For donors where there is adequate time, collection of one to two autologous red blood cell units can be accomplished. Other blood products, including red blood cell infusions, are rarely required and should be avoided unless absolutely indicated.

Median time to full recovery was approximately three weeks. Full recovery was reported by approximately 70 and 95 percent by one and three months after donation, respectively.

Studies of pediatric donors have also demonstrated that bone marrow harvest is safe in children [12-14]. As an example, the European Group for Blood and Marrow Transplantation Pediatrics Diseases Working Party reported no serious complications among 313 pediatric bone marrow donors [14]. However, the risk of requiring an allogeneic transfusion following bone marrow harvest was highest among patients less than four years old and those requiring a bone marrow harvest volume >20 mL/kg. Such donors should be considered for autologous blood donation prior to bone marrow harvest, and harvest volumes should not exceed 20 mL/kg.

Peripheral blood progenitor cell (PBPC) collection

Procedure — Progenitors and stem cells normally circulate in small numbers that are insufficient to collect for clinical use. Sufficient numbers of cells can usually be collected after the administration of granulocyte colony-stimulating factor (G-CSF, filgrastim) over four to six consecutive days. The leukapheresis procedure typically processes two to four blood volumes and takes three to six hours, depending on the donor size, donor progenitor/stem cell count, and how many stem cells are needed for the recipient. Approximately two-thirds of donors provide adequate progenitor/stem cells in a single session. The remainder requires a second session or, rarely, two more sessions [15]. (See "Sources of hematopoietic stem cells", section on 'Peripheral blood'.)

Toxicity of PBPC donation — The complication rate following mobilization and collection of PBPCs appears to be very low. Potential risks for the donor include those related to the administration of filgrastim (G-CSF) and to apheresis. Adequate venous access is required and, while most apheresis collections can be performed through peripheral access, occasional donors with small veins will require a temporary central venous catheter. 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'.)

Filgrastim is associated with mild to moderate generalized musculoskeletal pain in the vast majority of donors and with flu-like symptoms in a minority. Since the filgrastim is administered for five to six days, some donors may require acetaminophen or narcotic analgesics for several days prior to donation. The use of aspirin and nonsteroidal anti-inflammatory drugs is avoided because of the heightened risk of bleeding during the procedure and due to the thrombocytopenia, which may follow PBPC donation.

Donors may be thrombocytopenic for days or weeks after leukapheresis, but this is generally not clinically significant. The total white blood cell (WBC) count rises substantially during filgrastim administration, often achieving levels of 50 to 80 x 109/L, but elevation of the WBC count in and of itself does not entail any direct risk. However, some donor centers limit the use of filgrastim to keep the total WBC within local guidelines.

The following studies have evaluated the toxicity of PBPC donation:

In a prospective study of first-time unrelated donors from 2004 to 2009 by the NMDP, 6768 of 9494 (71 percent) donations were PBPCs collected over one (73 percent) or two days of apheresis [16]. Central venous access was required for 21 percent of women and 5 percent of men; however, in our experience, this rate of central venous catheter insertion is high and can be avoided by well trained personnel. Less than 3 percent of donors were hospitalized. The following complications were noted:

The majority of donors experienced mild to moderate (grade 1/2) generalized musculoskeletal pain within 24 hours of G-CSF administration. This pain peaked around day 5 and usually returned to baseline within one week.

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

Changes in peripheral blood counts were common. Most recovered to near-normal levels within one month. Leukocytosis occurred following G-CSF administration, while thrombocytopenia and anemia occurred following apheresis. On day 5 after G-CSF administration, the mean white blood cell count was approximately 40 x 109/L with 20 percent above 50 x 109/L and one donor above 100 x 109/L. Following a single day of apheresis, platelets decreased to <100 x 109/L in 26 percent and <50 x 109/L in <1 percent. After two days of apheresis, platelets were <100 x 109/L and <50 x 109/L in 50 and 1 percent, respectively. Platelets did not decrease to <20 x 109/L in any cases, and no platelet transfusions were required. Significant anemia (hemoglobin <8 g/dL) occurred in 0.1 and 0.2 percent of men and women, respectively.

More than half of donors reported resolution of toxicities by one week post-collection. Rates of complete recovery at one and six months were >90 and 100 percent, respectively.

In a separate analysis by the European Group for Blood and Marrow Transplantation (EBMT), a total of 51,024 donations were assessed: 27,770 were bone marrow and 23,254 were PBPC [15]. There were five donor deaths reported: one after a bone marrow donation and four after PBPC donation (incidence 0.98 per 10,000 donations). There were 37 severe adverse events (7.25/10,000): 12 in bone marrow donors (4.32/10,000) and 25 in PBPC donors (10.76/10,000). Thus, as in any medical procedure, there is a small but measurable risk of death or a severe adverse event.

A prospective 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) [17].

Safety of filgrastim in normal healthy donors — Filgrastim (G-CSF) use is associated with a very low rate of severe complications when administered to healthy donors. While mild splenic enlargement is common, cases of splenic rupture have been largely limited to case reports. Pregnant donors cannot receive filgrastim because the risk to the fetus has not been determined.

The following observations are illustrative of these potential complications:

A prospective study of spleen volume change in 309 donors who received filgrastim was evaluated by ultrasound [18]. Median spleen volume increased 1.47-fold (range: 0.63 to 2.60) on the first leukapheresis day and declined to near pretreatment levels at seven days after last leukapheresis, but no splenic ruptures in this cohort.

Adverse events following administration of filgrastim to donors with sickle cell trait are similar to those seen in the general population [19]. (See "Sickle cell trait", section on 'Hematopoietic stem cell donation'.)

In an analysis performed by the EBMT, 20 hematologic malignancies (3.92/10,000) were observed: eight after donating bone marrow and 12 after donating PBPC [15]. The observed incidence rate of hematologic malignancies did not exceed the expected incidence in an age- and sex-adjusted general population. Additional limited analyses have shown no increased incidence of leukemia in PBPC donors [15,20-22]. While reassuring, these studies do not completely rule out the possibility of an increased risk. Given the rarity of acute and chronic leukemias in the general population, it would be difficult to observe any increased risk unless the magnitude was very large. If an increased risk were found, it could be confounded by the use of related donors with a familial predisposition to leukemia.

WHICH PRODUCT IS PREFERRED? — Both peripheral blood progenitor cells (PBPCs) and bone marrow (BM) are acceptable hematopoietic cell sources for allogeneic transplantation. A choice between these must be made depending upon patient and donor preference. A discussion of the relative efficacy of PBPCs versus BM is presented separately. (See "Sources of hematopoietic stem cells", section on 'Allogeneic transplantation'.)

An opportunity to compare the physical and psychological consequences of BM and PBPC donation was provided by a Blood and Marrow Transplantation Clinical Trial Network (BMT-CTN) study in which unrelated patient-donor pairs were randomly assigned to BM or PBPC in the management of hematologic malignancies [23]. While the primary goals of the study were clinical outcomes of the recipients, comparisons of the effects on the 332 donors were also undertaken. Donors were evaluated both before and after donation with the following results:

BM donors – When compared with PBPC donors, BM donors experienced:

Less confusion, fewer concerns, and were better prepared before donation.

More pain, physical side effects, and limitation of social activities immediately after donation, and were more likely to require hospitalization.

A greater decrease in hemoglobin at one week following donation, but less of a decrease in white blood cell, neutrophils, mononuclear cell, and platelet counts [11].

Better psychological status and were more likely to indicate that the donation made their lives more meaningful [24].

PBPC donors – PBPC donors experienced more pain prior to donation, which was related to bone pain from the administration of filgrastim. They had less pain, physical side effects, and limitation of social activities immediately after donation.

In these and other studies and meta-analyses, there were no long-term differences in the experiences of the BM and PBPC donors including time to recovery [2,25,26].

CHILDREN AS DONORS — Children and adolescents under the age of 18 years are not allowed to serve as donors for nonfamily members. However, they may be asked to donate for a relative, most often a sibling. The use of cells collected from a minor sibling is associated with fewer transplant-related complications and greater overall survival for the recipient compared with the use of cells obtained from adult unrelated donors [27]. A survey of pediatric transplant clinicians demonstrated that the majority feels that it is acceptable to expose minor siblings to the risks of donation when it offers the family member the potential of benefit [28].

In 2010, the American Academy of Pediatrics (AAP) released a policy statement on the use of children as donors [29]. The statement outlined five conditions that the AAP recommends should be met for the use of a minor to serve as a donor.

There is no medically equivalent histocompatible adult relative who 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 further recommends that a donor advocate or similar individual who is educated in pediatric development and independent from the team directly responsible for the recipient's care is appointed for all potential minor donors.

Potential risks and benefit to minor donors — Bone marrow is the most common source of hematopoietic cells in pediatric transplantation [30]. The expected risks to minor bone marrow donors are similar to those experienced by adult donors. (See 'Complications' above.)

A study of 313 minor bone marrow donors identified pain requiring the use of medication as the most common complication of donation occurring in 50 percent of donors [14]. Older age was the only factor associated with greater risk of pain. Children aged four to eight years had a 3.3 times greater risk of pain compared with those less than four years, and those aged greater than eight years had a fivefold higher risk. The most frequent complications of anesthesia were vomiting (12 percent), sore throat (7 percent), hypotension (6 percent), tachycardia (4 percent), and bradycardia (0.6 percent). In a multivariate logistic regression model, only donor/recipient weight ratio <0.75 was associated with increased risk of cardiac complications, presumably due to the volume of marrow collected relative to donor size. Donor/recipient weight ratio <0.75 was also associated with greater risk of post-donation anemia.

Peripheral blood progenitor cell (PBPC) donation presents unique challenges to minor donors. The expected complications of granulocyte colony-stimulating factor (G-CSF) in children are similar to those experienced by adult donors, though pain is less frequently reported by minor donors [14,29]. Central venous access is required by most donors younger than 12 years of age, and the donor is placed under conscious sedation or general anesthesia [31]. Serious complications of central line placement in donors appear to be uncommon, occurring in less than 2 percent of donors in some series [14,27]. 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 less than 20 kg [31]. The larger the weight discrepancy between the donor and recipient, the greater the expected number of days of collection. More than half of the children required greater than one day of collection in a European Group for Blood and Marrow Transplantation (EBMT) study of 140 minor PBPC donors [14]. (See 'Toxicity of PBPC donation' above.)

There is no direct medical benefit to minor donors. The potential benefits are all expected to be psychosocial. There are few studies of the psychosocial effects of donation on minor donors. The literature suggests that a broad range of response to donation exists and they are impacted by many clinical, family, and psychosocial variables [32-34]. There is evidence to support that both donor and non-donor siblings experience stress related to their sibling's transplant.

A prospective longitudinal study of the health-related quality of life (HRQoL) of pediatric sibling donors found that approximately 20 percent of children who served as a stem cell donor for their sibling reported poor HRQoL at each of the time points assessed (pre-donation, four weeks following, and one year after donation); this was more prominent in the younger donors and differed from the parental report of the donor's HRQoL (which was likely to be higher) [35]. The study could not determine causality and other factors (eg, having a sick sibling) may have contributed to the reported HRQoL measures. The literature does not consistently indicate more adverse or positive impacts in minor donor siblings than non-donor siblings. There is a need for greater investigation in this area.

Selection of a minor donor — HLA-compatibility is the most important factor when selecting a minor donor. If the recipient is undergoing transplantation for an inherited condition, the potential donor must be adequately screened for the same disease or genetic carrier status in certain conditions. In some situations it is acceptable to use a donor who is a genetic carrier of the disease for which the transplant is being performed. There are no widely accepted guidelines for choosing a donor among equally HLA-compatible siblings who are unaffected by the recipient's underlying disease. The AAP recommends selecting the potential donor who is closest to the age of consent and avoiding donors who are developmentally unable to provide assent, when possible [29]. The selection of a donor for hematopoietic cell transplantation is discussed in more detail separately. (See "Donor selection for hematopoietic cell transplantation".)

SECOND DONATIONS — A marrow or peripheral blood progenitor cell (PBPC) donor may be contacted again if the recipient rejects the graft, relapses, or has an infection requiring additional immune cells.

Relapse — Much of the decision process involved in 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 – The original donor may be asked to donate peripheral blood lymphocytes in an effort to provide an enhanced immunologic recognition of the graft and generate a remission via the graft-versus-leukemia effect. This is known as a donor lymphocyte infusion. It does not require the administration of filgrastim, so it is generally easier than PBPC donation. (See "Immunotherapy for the prevention and treatment of relapse following allogeneic hematopoietic cell transplantation".)

Second hematopoietic cell donation – There are times when it is felt by the transplant clinician that a donor lymphocyte infusion would be inadequate and a second transplantation is planned. In that case, either PBPC or bone marrow may be requested. If the initial product was marrow, the transplant clinicians typically request PBPC for the second donation in case the iliac crest has not completely recovered hematopoiesis.

Graft failure — Graft rejection is uncommon, ranging from approximately 0.01 percent to as high as 10 to 15 percent depending on the type of transplant, 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. There is also an entity referred to as graft insufficiency or graft exhaustion in which it appears that too few stem cells were administered with the initial transplantation. Depending on the timing, clinical circumstances, and the purported etiology of the graft failure, the transplant team may request either marrow or PBPC for a second procedure.

Immune therapy — Providing immunologically competent cells to a patient who cannot clear an opportunistic infection may be life-saving [36-38]. Moreover, there are data that leukemic relapse can be treated with genetically engineered T cells to re-establish remission (eg, chimeric antigen receptor T cells) [39]. Both of these problems may be addressed with a second donation of peripheral blood lymphocytes. (See "Immunotherapy for the prevention and treatment of relapse following allogeneic hematopoietic cell transplantation".)

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 5th to 6th 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 10th to 12th 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

Donation for hematopoietic cell transplantation (HCT) is an altruistic and rewarding act of generosity. The evaluation of a potential donor must determine that the collection procedure is safe for the donor and the recipient.

The donor evaluation process includes a physical exam and comprehensive health assessment including screening for intravenous drug use, history of blood transfusions, pregnancies, abortions, tattoos, immunizations, and travel history. A standardized questionnaire (Donor History Questionnaires [DHQ] and medications lists from the AABB website) is used as a checklist to avoid missing critical information. (See 'Assessing for risks to the recipient' above.)

All donors must be fully informed of the risks and benefits of donation and sign appropriate consent forms indicating that they understand the risks and that they have been informed of alternative procedures. In order to avoid a conflict of interest and potential coercion, the stem cell collection evaluators are separate from the transplantation team. (See 'Informed consent' above.)

The transplant clinicians request either mobilized peripheral blood progenitor cells (PBPCs) or bone marrow. The donor can refuse either one or both of the procedures. With either procedure, approximately 5 percent of the donor's stem cells are collected. These cells will replace themselves in weeks to months, leaving the donor with a full complement of hematopoietic stem cells. There is often a period of discomfort that either precedes donation, as in the case of PBPC, or follows donation if marrow is collected. In both cases, donors return to fully normal performance over the course of days to weeks after the donation.

Bone marrow or PBPC donors should avoid potential bone marrow suppressive agents, such as alcohol or clopidogrel, for at least 14 days before donation and avoid nonsteroidal anti-inflammatory medications such as ibuprofen or naproxen sodium for 24 hours prior to donation. For bone marrow donors with a hemoglobin of <13 g/dL, we suggest iron supplementation for one month prior to and after donation (Grade 2C). (See 'Preoperative assessment' above.)

Bone marrow donation is performed under general or regional anesthesia and is therefore subject to risks associated with these forms of anesthesia. Following collection, donors typically experience mild to moderate back or hip pain, fatigue, and transient changes in peripheral blood cell counts. Donors are asked to refrain from heavy lifting and high impact exercises for approximately six weeks to allow the iliac crest to heal. Donors often require iron replacement and analgesia after the collection. Serious complications of bone marrow harvest are extremely rare. (See 'Complications' above.)

Potential risks associated with mobilization and collection of PBPCs include those related to the administration of filgrastim and to apheresis. Some donors may require acetaminophen or narcotic analgesics for several days prior to donation to control the generalized musculoskeletal pain associated with filgrastim. Most apheresis collections can be performed through peripheral access. Approximately two-thirds of donors provide adequate stem/progenitor cells in a single three- to six-hour session. The remainder requires two or more collections. (See 'Peripheral blood progenitor cell (PBPC) collection' above.)

Filgrastim use is associated with a very low rate of severe complications when administered to normal healthy donors. While mild splenic enlargement is common, cases of splenic rupture have been largely limited to case reports. There is no measurable association with the development of leukemia. Pregnant donors cannot receive filgrastim. (See 'Safety of filgrastim in normal healthy donors' above.)

Children and adolescents under the age of 18 years are not allowed to serve as donors for nonfamily members. However, they may be asked to donate for a relative, most often a sibling. (See 'Children as donors' above.)

A donor may be contacted again if the recipient rejects the graft, relapses, or has an infection requiring additional immune cells. (See 'Second donations' above.)

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Topic 96033 Version 19.0

References

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