Evaluation of the hematopoietic cell transplantation donor
- Joseph H Antin, MD
Joseph H Antin, MD
- Professor of Medicine, Harvard Medical School
- Chief, Stem Cell Transplantation Program, Dana-Farber/Brigham and Women’s Cancer Center
- Christine N Duncan, MD
Christine N Duncan, MD
- Assistant Professor of Pediatrics
- Harvard Medical School
Allogeneic hematopoietic cell transplantation (HCT) 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 or peripheral blood of a related or unrelated donor. Both 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. 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). 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".)
In contrast to most organ transplantation, hematopoietic stem cells are a renewable resource that, with the exception of umbilical cord blood donation, requires the participation of a donor. 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.
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" and "Collection and storage of umbilical cord blood for hematopoietic cell transplantation" and "Selection of an umbilical cord blood graft for hematopoietic cell transplantation" and "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 American Association of Blood Banks (AABB), 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 the donor's physical health 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. Often, the stringent prohibition of donors at risk of transmitting communicable diseases is waived if use of the donor is determined to be in the best interest of the patient.
- http://factwebsite.org/Inner.aspx?id=163 (Accessed on February 17, 2015).
- Garcia MC, Chapman JR, Shaw PJ, et al. Motivations, experiences, and perspectives of bone marrow and peripheral blood stem cell donors: thematic synthesis of qualitative studies. Biol Blood Marrow Transplant 2013; 19:1046.
- Kennedy GA, Morton J, Western R, et al. Impact of stem cell donation modality on normal donor quality of life: a prospective randomized study. Bone Marrow Transplant 2003; 31:1033.
- Munzenberger N, Fortanier C, Macquart-Moulin G, et al. Psychosocial aspects of haematopoietic stem cell donation for allogeneic transplantation: how family donors cope with this experience. Psychooncology 1999; 8:55.
- Leitner GC, Baumgartner K, Kalhs P, et al. Regeneration, health status and quality of life after rhG-CSF-stimulated stem cell collection in healthy donors: a cross-sectional study. Bone Marrow Transplant 2009; 43:357.
- Miller JP, Perry EH, Price TH, et al. Recovery and safety profiles of marrow and PBSC donors: experience of the National Marrow Donor Program. Biol Blood Marrow Transplant 2008; 14:29.
- Pulsipher MA, Chitphakdithai P, Logan BR, et al. Lower risk for serious adverse events and no increased risk for cancer after PBSC vs BM donation. Blood 2014; 123:3655.
- Buckner CD, Clift RA, Sanders JE, et al. Marrow harvesting from normal donors. Blood 1984; 64:630.
- Sanders J, Buckner CD, Bensinger WI, et al. Experience with marrow harvesting from donors less than two years of age. Bone Marrow Transplant 1987; 2:45.
- Styczynski J, Balduzzi A, Gil L, et al. Risk of complications during hematopoietic stem cell collection in pediatric sibling donors: a prospective European Group for Blood and Marrow Transplantation Pediatric Diseases Working Party study. Blood 2012; 119:2935.
- Halter J, Kodera Y, Ispizua AU, et al. Severe events in donors after allogeneic hematopoietic stem cell donation. Haematologica 2009; 94:94.
- Pulsipher MA, Chitphakdithai P, Logan BR, et al. Acute toxicities of unrelated bone marrow versus peripheral blood stem cell donation: results of a prospective trial from the National Marrow Donor Program. Blood 2013; 121:197.
- Pulsipher MA, Chitphakdithai P, Miller JP, et al. Adverse events among 2408 unrelated donors of peripheral blood stem cells: results of a prospective trial from the National Marrow Donor Program. Blood 2009; 113:3604.
- Shaw BE, Confer DL, Hwang W, Pulsipher MA. A review of the genetic and long-term effects of G-CSF injections in healthy donors: a reassuring lack of evidence for the development of haematological malignancies. Bone Marrow Transplant 2015; 50:334.
- Stiff PJ, Bensinger W, Abidi MH, et al. Clinical and ultrasonic evaluation of spleen size during peripheral blood progenitor cell mobilization by filgrastim: results of an open-label trial in normal donors. Biol Blood Marrow Transplant 2009; 15:827.
- Kang EM, Areman EM, David-Ocampo V, et al. Mobilization, collection, and processing of peripheral blood stem cells in individuals with sickle cell trait. Blood 2002; 99:850.
- Hasenclever D, Sextro M. Safety of AlloPBPCT donors: biometrical considerations on monitoring long term risks. Bone Marrow Transplant 1996; 17 Suppl 2:S28.
- Anderlini P, Chan FA, Champlin RE, et al. Long-term follow-up of normal peripheral blood progenitor cell donors treated with filgrastim: no evidence of increased risk of leukemia development. Bone Marrow Transplant 2002; 30:661.
- Anasetti C, Logan BR, Lee SJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med 2012; 367:1487.
- Switzer GE, Bruce JG, Harrington D, et al. Health-related quality of life of bone marrow versus peripheral blood stem cell donors: a prespecified subgroup analysis from a phase III RCT-BMTCTN protocol 0201. Biol Blood Marrow Transplant 2014; 20:118.
- Bredeson C, Leger C, Couban S, et al. An evaluation of the donor experience in the canadian multicenter randomized trial of bone marrow versus peripheral blood allografting. Biol Blood Marrow Transplant 2004; 10:405.
- Siddiq S, Pamphilon D, Brunskill S, et al. Bone marrow harvest versus peripheral stem cell collection for haemopoietic stem cell donation in healthy donors. Cochrane Database Syst Rev 2009; :CD006406.
- Grupp SA, Frangoul H, Wall D, et al. Use of G-CSF in matched sibling donor pediatric allogeneic transplantation: a consensus statement from the Children's Oncology Group (COG) Transplant Discipline Committee and Pediatric Blood and Marrow Transplant Consortium (PBMTC) Executive Committee. Pediatr Blood Cancer 2006; 46:414.
- Chan KW, Gajewski JL, Supkis D Jr, et al. Use of minors as bone marrow donors: current attitude and management. A survey of 56 pediatric transplantation centers. J Pediatr 1996; 128:644.
- American Academy of Pediatrics. Committee on Bioethics. Children as hematopoietic stem cell donors. Pediatrics 2010; 125:392.
- Pulsipher MA, Levine JE, Hayashi RJ, et al. Safety and efficacy of allogeneic PBSC collection in normal pediatric donors: the pediatric blood and marrow transplant consortium experience (PBMTC) 1996-2003. Bone Marrow Transplant 2005; 35:361.
- Wiener LS, Steffen-Smith E, Fry T, Wayne AS. Hematopoietic stem cell donation in children: a review of the sibling donor experience. J Psychosoc Oncol 2007; 25:45.
- Packman WL, Crittenden MR, Schaeffer E, et al. Psychosocial consequences of bone marrow transplantation in donor and nondonor siblings. J Dev Behav Pediatr 1997; 18:244.
- Williams S, Green R, Morrison A, et al. The psychosocial aspects of donating blood stem cells: the sibling donor perspective. J Clin Apher 2003; 18:1.
- Weisz V, Robbennolt JK. Risks and benefits of pediatric bone marrow donation: a critical need for research. Behav Sci Law 1996; 14:375.
- Leen AM, Bollard CM, Mendizabal AM, et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood 2013; 121:5113.
- Leen AM, Heslop HE, Brenner MK. Antiviral T-cell therapy. Immunol Rev 2014; 258:12.
- Papadopoulou A, Gerdemann U, Katari UL, et al. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med 2014; 6:242ra83.
- Kochenderfer JN, Dudley ME, Carpenter RO, et al. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood 2013; 122:4129.
- CANDIDACY FOR DONATION
- Donor guidelines
- Assessing for risks to the recipient
- Informed consent
- Assessing for risks to the donor
- - Psychological effects
- - Bone marrow donation
- Preoperative assessment
- Bone marrow collection
- - Peripheral blood progenitor cell (PBPC) collection
- Toxicity of PBPC donation
- Safety of filgrastim in normal healthy donors
- WHICH PRODUCT IS PREFERRED?
- CHILDREN AS DONORS
- Potential risks and benefit to minor donors
- Selection of a minor donor
- SECOND DONATIONS
- Graft failure
- Immune therapy
- INFORMATION FOR PATIENTS