Author: Kathryn Ciccolini DNP, AGACNP-BC, OCN, Mount Sinai Hospital
Allogeneic hematopoietic stem cell transplantation (AlloSCT) is potentially a curative treatment for various hematologic malignancies. Patients referred for evaluation for an AlloSCT to the bone marrow transplant (BMT) program at Mount Sinai Hospital (MSH) are immediately evaluated for donor availability. The process of a donor search is multifaceted requiring a specialized and highly unique skillset. At MSH, our group of transplant nurse coordinators and administrative donor coordinators have extensive training and are one of the very few members in the hospital who perform this exceptionally rewarding patient care coordination. Although, identifying a donor is not so straightforward, let’s delve behind-the scenes to learn more.
Basics of HLA and Transplantation
There are many factors that can influence transplantation outcome, one of which is an absolute pre-requisite and a paramount criterion for an alloSCT, donor-recipient histocompatibility (matching of donor and recipient human leukocyte antigen [HLA] protein). In short, HLA proteins are cell-surface inherited proteins found on the major histocompatibility complex (MHC) and play a major role in the immune defense system’s ability to identify self from non-self (NMDP 2021). The most pertinent genes for transplantation belong to MHC Class I (HLA-A, HLA-B, and HLA-C), and MHC Class II (HLA-DR, HLA-DQ, and HLA-DP) (Furst et al, 2019). Detailed HLA typing is used to determine match grade between recipient and donor and donor eligibility. Matched HLA allows for engraftment and reduces the risk of graft-versus-host disease (GVHD) and graft rejection. It is also the most consistent, predictive factor for outcome post HSCT from unrelated donors (Petersdorf, 2016). Donors can be related or unrelated as the source of stem cells resulting in several possible approaches for transplantation. Related donors can either be full match or half match thus siblings, children, parents and even second degree relatives can be considered (NMDP 2022; Sugita, 2019). While an HLA-identical matched sibling donor remains the preferred stem cell source for allogeneic stem cell transplantation, only 30% of patients clinical situation meet this standard leaving the remaining 70% requiring further exploration in other donor sources emphasizing the importance of volunteer donor registries such as National Marrow Donor Program (NMDP) (Ayuk, & Balduzzi, 2019; Petersdorf, 2016; Sugita, 2019). Factors to consider for a successful transplant beyond HLA are donor age, CMV status, cell dose, donor sex, pregnancy history, ABO compatibility, and the presence of donor specific HLA antibodies (DSA) (Ayuk, & Balduzzi, 2019).
At the initial BMT clinic visit, the patient (recipient) is extensively educated on the donor search process for their transplant and is assessed for their initial HLA lab markers by blood test. The recipient completes a family information sheet which is used to arrange initial HLA related donor HLA blood testing. The selection of related donors per recipient can vary with sometimes having over ten options, all of which the interdisciplinary team manages simultaneously. The HLA results of both recipient and donor(s) are compared to assess their match degree. All potentially qualified donors are notified and assessed for willingness to voluntarily donate to share the results with the recipient. The prospective donors are screened for eligibility and suitability by a transplant physician (who is not primary physician of the recipient) and nurse coordinator which includes a comprehensive history and physical evaluation, infectious disease screening and educational session on modes of donation (bone marrow harvest and peripheral blood stem cell), collection process, and medical clearance. Once a donor is identified, and donation stem cell source preference is established by the clinical team and donor, they are brought to the apheresis center for a tour, the nurse coordinator arranges mobilization therapy, addresses central venous catheter requirements, and organizes their collection.
However, when a related donor search is not feasible or did not yield a potential donor, the nurse coordinators initiate a preliminary search through the NMDP, a national resource for facilitating unrelated donor and cord blood stem cell transplants. This is the only organization in the USA that matches unrelated volunteer donors, arranges collections and transportations of stem cells, manages collection and analysis of multi-center data on both donor and cord blood unit (CBU) process, stem cell donation side effects, patient transplant outcomes, and histocompatibility, and maintains a research sample repository (NMDP 2021). Preliminary searches are often proactively done in tandem of conducting related donor searches in the circumstance a suitable related donor is not found. This search identifies potential unrelated stem cell donors and CBU representing a “snap shot’ of potential matches at a given time which can help shape a recipient’s treatment plan. When potential donors are selected from this search after thorough collaborative clinical team discussion, the search is formalized by requesting confirmatory HLA testing on identified potential unrelated donors. The coordinators work closely with NMDP case manager on unrelated donor workup, eligibility and clearance domestically, nationally, and internationally requiring consistent follow up and assurance of donor medical clearance. Once the donor is identified and cleared, the team works with the NMDP case manager on the donor collection, delivery of cells to MSH requiring tremendous logistical coordinator with NMDP, recipient, family, our Cell Therapy Lab, and other members of the BMT program.
Challenges with Donation Coordination
Besides the inherently complex process from donor identification to recipient transfusion, there are many donor-related challenges the coordinators address including physical symptoms and often moral distress. Donors may experience feelings of ambivalence, grief, anguish, fear, pressure in being responsible for the recipient’s outcomes, feeling pressured (Gutierrez-Aguirre et al. 2021). The coordinators are heavily relied upon to demystify the process of what it means to be a donor, address psychosocial concerns, dispel misconceptions of donation, educate on expected adverse events associated with donation, and could be faced with donors with religious conviction or occupational barriers (Garcia et al, 2013; NMDP 2022). Further, the coordinators face challenges with donors living in remote areas with limited access to medical care, communicating with donors who are in different time zones and in different languages, governmental import and export restrictions for international donors, and travel limitations for donors with visa issues. A large majority of the donors registered in the database are of Western European ancestry impeding HLA match access for certain ethnic origins (Tiercy, 2016). Our geographic location and the diversity of New York City complicates finding a well-matched related or unrelated donor resulting in exploration of alternative donors allowing for greater degree of mismatch.
It takes up to an estimated ten hours per recipient to perform preliminary searches, formalize donor searches to clear and collect a donor, and coordinate cell delivery to MSH and recipient admission given exquisite and meticulous logistical coordination and attention. Between 2020 and 2021, 469 related donors were typed requiring coordination of HLA testing and counseling on donor matches and process. I hope this article sheds light on the value of a strong donor search coordination program and the highly unique skills needed to provide quality care within our bone marrow transplant and cellular therapy program at Mount Sinai Hospital.
Ayuk, F. & Balduzzi, A. (2019). The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th edition. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK554000/
Furst, D., Neuchel, C., Tsamadou, C., Schrezenmeier, H., & Mytilineos, J. (2019). HLA Matching in Unrelated Stem Cell Transplantation up to Date. Transfusion Medicine and Hemotherapy, 46(5), 326-336.
Garcia, M.C, Chapman, J.R., Shaw, P.J., Gottlieb, D.J, Ralph, A., Craig, J.C., & Tong, A. (2013). Motivations, Experiences, and Perspectives of Bone Marrow and Peripheral Blood Stem Cell Donors: Thematic Synthesis of Qualitative Studies. Biology of Blood and Marrow Transplantation, 19(7), 1046-1058.
Gutierrez-Aguirre, C.H., Jaime-Perez, J.C., de la Garza-Salazar, F., Guerrero-Gonzalez, G., Guzman-Lopez, A., Ruiza-Arguelles, G.J., Gomez-Almaguer, D., & Cantu-Rodriguez, O.G. (2021). Moral Distress: Its Manifestations in Healthy Donors during Peripheral Blood Hematopoietic Stem Cell Harvesting. Transplantation and Cellular Therapy, 27(10), 853-858.
National Marrow Donor Program (2021). Manual of Operations Chapter 2: NMDP Search and Matching Process. Retrieved from https://network.bethematchclinical.org/transplant-centers/policies-and-protocols/tc-manual-of-operations/
National Marrow Donor Program (2022). HLA Matching. Retrieved from: https://bethematch.org/
Petersdorf, E.W. (2016). Mismatched Unrelated Donor Transplantation. Semin Hematol, 53(4), 230–236.
Sugita, 2019. Allogeneic hematopoietic stem cell transplantation for hematological malignancies: an algorithm for donor selection. Rinsho Ketsueki, 60(6), 626-634.Tiercy, J. (2016). How to select the best available related or unrelated donor of hematopoietic stem cells? Haematologica, 101(6), 680-687.