Optimizing Access to Unrelated Donors in Canada: Re-Examining the Importance of Donor Factors on Outcomes Following Hematopoietic Cell Transplantation
Abstract
:1. Introduction
2. Evolving Trends in Allogeneic Transplantation: The Canadian Context
3. Selecting the Optimal Donor
Role of HLA Matching
4. Donor Factors to Consider beyond HLA
4.1. Donor Age
4.2. Donor Sex at Birth and Parity Status of Female Donors
4.3. Donor CMV Status
4.4. Donor ABO Status
4.5. Cytokine Profiles, KIR Matching, and Other Factors
4.6. Selection and Use of Domestic Donors
4.7. Availability of Donors
5. Discussion: How Can Registries Reflect the Changing Needs? A Closer Look at the CBS Stem Cell Registry
6. Conclusions and Future Directions: Considerations for Unrelated Donor Selection
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Snowden, J.A.; Sánchez-Ortega, I.; Corbacioglu, S.; Basak, G.W.; Chabannon, C.; de la Camara, R.; Dolstra, H.; Duarte, R.F.; Glass, B.; Greco, R.; et al. Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: Current practice in Europe, 2022. Bone Marrow Transplant. 2022, 57, 1217–1239. [Google Scholar] [CrossRef] [PubMed]
- Kanate, A.S.; Majhail, N.S.; Savani, B.N.; Bredeson, C.; Champlin, R.E.; Crawford, S.; Giralt, S.A.; LeMaistre, C.F.; Marks, D.I.; Omel, J.L.; et al. Indications for Hematopoietic Cell Transplantation and Immune Effector Cell Therapy: Guidelines from the American Society for Transplantation and Cellular Therapy. Biol. Blood Marrow Transplant. 2020, 26, 1247–1256. [Google Scholar] [CrossRef]
- Besse, K.; Maiers, M.; Confer, D.; Albrecht, M. On Modeling Human Leukocyte Antigen–Identical Sibling Match Probability for Allogeneic Hematopoietic Cell Transplantation: Estimating the Need for an Unrelated Donor Source. Biol. Blood Marrow Transplant. 2016, 22, 410–417. [Google Scholar] [CrossRef]
- Kollman, C.; Spellman, S.R.; Zhang, M.-J.; Hassebroek, A.; Anasetti, C.; Antin, J.H.; Champlin, R.E.; Confer, D.L.; DiPersio, J.F.; Fernandez- Viña, M.; et al. The effect of donor characteristics on survival after unrelated donor transplantation for hematologic malignancy. Blood 2016, 127, 260–267. [Google Scholar] [CrossRef] [PubMed]
- Shaw, B.E.; Logan, B.R.; Spellman, S.R.; Marsh, S.G.E.; Robinson, J.; Pidala, J.; Hurley, C.; Barker, J.; Maiers, M.; Dehn, J.; et al. Development of an Unrelated Donor Selection Score Predictive of Survival after HCT: Donor Age Matters Most. Biol. Blood Marrow Transplant. 2018, 24, 1049–1056. [Google Scholar] [CrossRef]
- Switzer, G.E.; Bruce, J.G.; Myaskovsky, L.; DiMartini, A.; Shellmer, D.; Confer, D.L.; Abress, L.K.; King, R.J.; Harnaha, A.G.; Ohngemach, S.; et al. Race and ethnicity in decisions about unrelated hematopoietic stem cell donation. Blood 2013, 121, 1469–1476. [Google Scholar] [CrossRef]
- Bacigalupo, A.; Lamparelli, T.; Bruzzi, P.; Guidi, S.; Alessandrino, P.E.; Di Bartolomeo, P.; Oneto, R.; Bruno, B.; Barbanti, M.; Sacchi, N.; et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood 2001, 98, 2942–2947. [Google Scholar] [CrossRef]
- Finke, J.; Bethge, W.A.; Schmoor, C.; Ottinger, H.D.; Stelljes, M.; Zander, A.R.; Volin, L.; Ruutu, T.; Heim, D.A.; Schwerdtfeger, R.; et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: A randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009, 10, 855–864. [Google Scholar] [CrossRef] [PubMed]
- Walker, I.; Panzarella, T.; Couban, S.; Couture, F.; Devins, G.; Elemary, M.; Gallagher, G.; Kerr, H.; Kuruvilla, J.; Lee, S.J.; et al. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: A randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016, 17, 164–173. [Google Scholar] [CrossRef]
- Shaw, B.E.; Jimenez-Jimenez, A.M.; Burns, L.J.; Logan, B.R.; Khimani, F.; Shaffer, B.C.; Shah, N.N.; Mussetter, A.; Tang, X.-Y.; McCarty, J.M.; et al. National Marrow Donor Program–sponsored multicenter, phase II trial of HLA-mismatched unrelated donor bone marrow transplantation using post-transplant cyclophosphamide. J. Clin. Oncol. 2021, 39, 1971–1982. [Google Scholar] [CrossRef]
- Mehta, R.S.; Saliba, R.M.; Rondon, G.; Al-Atrash, G.; Bashir, Q.; Hosing, C.M.; Kebriaei, P.; Khouri, I.; Nieto, Y.; Oran, B.; et al. Post-Transplantation Cyclophosphamide Versus Tacrolimus and Methotrexate Graft-Versus-Host Disease Prophylaxis for HLA-Matched Donor Transplantation. Transplant. Cell. Ther. 2022, 28, 695.e1–695.e10. [Google Scholar] [CrossRef] [PubMed]
- Seftel, M.D.; Pasic, I.; Parmar, G.; Bucher, O.; Allan, D.S.; Bhella, S.; Hay, K.A.; Ikuomola, O.; Musto, G.; Prica, A.; et al. Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-Based Cohort Study. Curr. Oncol. 2023, 30, 9953–9967. [Google Scholar] [CrossRef]
- Centre for International Blood and Marrow Transplant Research US Summary Slides. Available online: https://cibmtr.org/CIBMTR/Resources/Summary-Slides-Reports (accessed on 7 April 2024).
- Passweg, J.R.; Baldomero, H.; Ciceri, F.; de la Cámara, R.; Glass, B.; Greco, R.; Hazenberg, M.D.; Kalwak, K.; McLornan, D.P.; Neven, B.; et al. Hematopoietic cell transplantation and cellular therapies in Europe 2022. CAR-T activity continues to grow; transplant activity has slowed: A report from the EBMT. Bone Marrow Transplant. 2024. [Google Scholar] [CrossRef]
- Bolaños-Meade, J.; Hamadani, M.; Wu, J.; Al Malki, M.M.; Martens, M.J.; Runaas, L.; Elmariah, H.; Rezvani, A.R.; Gooptu, M.; Larkin, K.T.; et al. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. N. Engl. J. Med. 2023, 388, 2338–2348. [Google Scholar] [CrossRef] [PubMed]
- Yu, N.; Askar, M.; Wadsworth, K.; Gragert, L.; Fernández-Viña, M.A. Current HLA testing recommendations to support HCT. Hum. Immunol. 2022, 83, 665–673. [Google Scholar] [CrossRef] [PubMed]
- Pidala, J.; Lee, S.J.; Ahn, K.W.; Spellman, S.; Wang, H.-L.; Aljurf, M.; Askar, M.; Dehn, J.; Fernandez Viña, M.; Gratwohl, A.; et al. Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation. Blood 2014, 124, 2596–2606. [Google Scholar] [CrossRef] [PubMed]
- Kekre, N.; Antin, J.H. Hematopoietic stem cell transplantation donor sources in the 21st century: Choosing the ideal donor when a perfect match does not exist. Blood 2014, 124, 334–343. [Google Scholar] [CrossRef] [PubMed]
- Sideri, A.; Neokleous, N.; Brunet De La Grange, P.; Guerton, B.; Le Bousse Kerdilles, M.-C.; Uzan, G.; Peste-Tsilimidos, C.; Gluckman, E. An overview of the progress on double umbilical cord blood transplantation. Haematologica 2011, 96, 1213–1220. [Google Scholar] [CrossRef] [PubMed]
- Verneris, M.R.; Lee, S.J.; Ahn, K.W.; Wang, H.-L.; Battiwalla, M.; Inamoto, Y.; Fernandez-Vina, M.A.; Gajewski, J.; Pidala, J.; Munker, R.; et al. HLA Mismatch Is Associated with Worse Outcomes after Unrelated Donor Reduced-Intensity Conditioning Hematopoietic Cell Transplantation: An Analysis from the Center for International Blood and Marrow Transplant Research. Biol. Blood Marrow Transplant. 2015, 21, 1783–1789. [Google Scholar] [CrossRef]
- Gragert, L.; Eapen, M.; Williams, E.; Freeman, J.; Spellman, S.; Baitty, R.; Hartzman, R.; Rizzo, J.D.; Horowitz, M.; Confer, D.; et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N. Engl. J. Med. 2014, 371, 339–348. [Google Scholar] [CrossRef]
- Abid, M.B.; Estrada-Merly, N.; Zhang, M.-J.; Chen, K.; Allan, D.; Bredeson, C.; Sabloff, M.; Guru Murthy, G.S.; Badar, T.; Hashmi, S.; et al. Impact of Donor Age on Allogeneic Hematopoietic Cell Transplantation Outcomes in Older Adults with Acute Myeloid Leukemia. Transplant. Cell. Ther. 2023, 29, 578.e1–578.e9. [Google Scholar] [CrossRef]
- Abid, M.B.; Estrada-Merly, N.; Zhang, M.J.; Chen, K.; Bredeson, C.; Allan, D.; Sabloff, M.; Marks, D.I.; Litzow, M.; Hourigan, C.; et al. Younger Matched Unrelated Donors Confer Decreased Relapse Risk Compared to Older Sibling Donors in Older Patients with B Cell Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation. Transplant. Cell. Ther. 2023, 29, 611–618. [Google Scholar] [CrossRef]
- Little, A.; Green, A.; Harvey, J.; Hemmatpour, S.; Latham, K.; Marsh, S.G.E.; Poulton, K.; Sage, D. BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation. Int. J. Immunogenet. 2016, 43, 263–286. [Google Scholar] [CrossRef]
- Loren, A.W.; Bunin, G.R.; Boudreau, C.; Champlin, R.E.; Cnaan, A.; Horowitz, M.M.; Loberiza, F.R.; Porter, D.L. Impact of donor and recipient sex and parity on outcomes of HLA-identical sibling allogeneic hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. 2006, 12, 758–769. [Google Scholar] [CrossRef]
- Parmar, G.; Allan, D.S.; Morris, G.; Dibdin, N.; Ganz, K.; Mostert, K.; Paulson, K.; Petraszko, T.; Stevens, N.; Seftel, M.D. The effect of the COVID-19 pandemic on unrelated allogeneic hematopoietic donor collections and safety. Curr. Oncol. 2023, 30, 3549–3556. [Google Scholar] [CrossRef]
- Lindsay, J.; Othman, J.; Kerridge, I.; Fay, K.; Stevenson, W.; Arthur, C.; Chen, S.C.-A.; Kong, D.C.M.; Pergam, S.A.; Liu, C.; et al. Cytomegalovirus (CMV) management in allogeneic hematopoietic cell transplantation: Pre-transplant predictors of survival, reactivation, and spontaneous clearance. Transpl. Infect. Dis. 2021, 23, e13548. [Google Scholar] [CrossRef]
- Kalra, A.; Williamson, T.; Daly, A.; Savoie, M.L.; Stewart, D.A.; Khan, F.; Storek, J. Impact of Donor and Recipient Cytomegalovirus Serostatus on Outcomes of Antithymocyte Globulin–Conditioned Hematopoietic Cell Transplantation. Biol. Blood Marrow Transplant. 2016, 22, 1654–1663. [Google Scholar] [CrossRef] [PubMed]
- Sheppard, D.; Tay, J.; Bryant, A.; McDiarmid, S.; Huebsch, L.; Tokessy, M.; Hamelin, L.; Saidenberg, E.; Bredeson, C. Major ABO-incompatible BMT: Isohemagglutinin reduction with plasma exchange is safe and avoids graft manipulation. Bone Marrow Transplant. 2013, 48, 953–957. [Google Scholar] [CrossRef]
- Sorg, N.; Poppe, C.; Bunos, M.; Wingenfeld, E.; Hümmer, C.; Krämer, A.; Stock, B.; Seifried, E.; Bonig, H. Red blood cell depletion from bone marrow and peripheral blood buffy coat: A comparison of two new and three established technologies. Transfusion 2015, 55, 1275–1282. [Google Scholar] [CrossRef]
- Guru Murthy, G.S.; Logan, B.R.; Bo-Subait, S.; Beitinjaneh, A.; Devine, S.; Farhadfar, N.; Gowda, L.; Hashmi, S.; Lazarus, H.; Nathan, S.; et al. Association of ABO mismatch with the outcomes of allogeneic hematopoietic cell transplantation for acute leukemia. Am. J. Hematol. 2023, 98, 608–619. [Google Scholar] [CrossRef] [PubMed]
- Tripathi, G.; Khanolkar, R.A.; Faridi, R.M.; Kalra, A.; Dharmani-Khan, P.; Shabani-Rad, M.T.; Berka, N.; Daly, A.; Storek, J.; Khan, F.M. Donor Genetic Predisposition to High Interleukin-10 Production Appears Protective against Acute Graft-Versus-Host Disease. Int. J. Mol. Sci. 2022, 23, 15888. [Google Scholar] [CrossRef] [PubMed]
- McDermott, D.H.; Conway, S.E.; Wang, T.; Ricklefs, S.M.; Agovi, M.A.; Porcella, S.F.; Tran, H.T.B.; Milford, E.; Spellman, S.; Abdi, R. Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation. Blood 2010, 115, 2311–2318. [Google Scholar] [CrossRef]
- Baron, C.; Somogyi, R.; Greller, L.D.; Rineau, V.; Wilkinson, P.; Cho, C.R.; Cameron, M.J.; Kelvin, D.J.; Chagnon, P.; Roy, D.-C.; et al. Prediction of graft-versus-host disease in humans by donor gene-expression profiling. PLoS Med. 2007, 4, e23. [Google Scholar] [CrossRef]
- Faridi, R.M.; Kemp, T.J.; Dharmani-Khan, P.; Lewis, V.; Tripathi, G.; Rajalingam, R.; Daly, A.; Berka, N.; Storek, J.; Khan, F.M. Donor-Recipient Matching for KIR Genotypes Reduces Chronic GVHD and Missing Inhibitory KIR Ligands Protect against Relapse after Myeloablative, HLA Matched Hematopoietic Cell Transplantation. PLoS ONE 2016, 11, e0158242. [Google Scholar] [CrossRef]
- Gibson, C.J.; Kim, H.T.; Zhao, L.; Murdock, H.M.; Hambley, B.; Ogata, A.; Madero-Marroquin, R.; Wang, S.; Green, L.; Fleharty, M.; et al. Donor Clonal Hematopoiesis and Recipient Outcomes after Transplantation. J. Clin. Oncol. 2022, 40, 189–201. [Google Scholar] [CrossRef]
- Greco-Stewart, V.; Kiernan, J.; Killeen, D.; Haun, S.; Mercer, D.; Young, K.; Liwski, R.S.; Allan, D.S. Unrelated donor choices for allogeneic hematopoietic cell transplantation in Canada: An evaluation of factors influencing donor selection. Transfusion 2018, 58, 718–725. [Google Scholar] [CrossRef]
- Greco-Stewart, V.; Elmoazzen, H.; Morris, G.; Guo, Y.; Langdon, C.; Mercer, D.; Dibdin, N.; Allan, D.S. Improved access to better HLA-matched unrelated donors for hematopoietic cell transplantation for Canadian patients: Analysis of donor workups and selections in 2018. Transfusion 2020, 60, 1508–1518. [Google Scholar] [CrossRef]
- Allan, D.S.; Green, M.; Morris, G.; Weiss, J.T.; Dibdin, N.; Mercer, D.; Seftel, M. Demand and usage of unrelated donor products for allogeneic haematopoietic cell transplantation during the COVID-19 pandemic: A Canadian Blood Services Stem Cell Registry analysis. Vox Sang. 2022, 117, 1121–1125. [Google Scholar] [CrossRef] [PubMed]
- Nawas, M.T.; Shah, G.L.; Feldman, D.R.; Ruiz, J.D.; Robilotti, E.V.; Aslam, A.A.; Dundas, M.; Kamboj, M.; Barker, J.N.; Cho, C.; et al. Cellular therapy during COVID-19: Lessons learned and preparing for subsequent waves. Transplant. Cell. Ther. 2021, 27, 438.e1–438.e6. [Google Scholar] [CrossRef]
- Auletta, J.J.; Novakovich, J.L.; Stritesky, G.L.; Newman, J.; Fridy-Chesser, S.T.; Hailperin, K.; Devine, S.M. Meeting the demand for unrelated donors in the midst of the COVID-19 pandemic: Rapid adaptations by the National Marrow Donor Program and its network partners ensured a safe supply of donor products. Transplant. Cell. Ther. 2021, 27, 133–141. [Google Scholar] [CrossRef]
- Mengling, T.; Rall, G.; Bernas, S.N.; Astreou, N.; Bochert, S.; Boelk, T.; Buk, D.; Burkard, K.; Endert, D.; Gnant, K.; et al. Stem cell donor registry activities during the COVID-19 pandemic: A field report by DKMS. Bone Marrow Transplant. 2021, 56, 798–806. [Google Scholar] [CrossRef]
- Monaghan, M.; Yi, Q.-L.; Green, M.; Campbell, T.; Weiss, J.T.; Dibdin, N.; Mercer, D.; Elmoazzen, H.; Allan, D.S. Factors associated with registrant availability for unrelated adult donor hematopoietic stem cell donation: Analysis of the Stem Cell Registry at Canadian Blood Services. Transfusion 2021, 61, 24–48. [Google Scholar] [CrossRef] [PubMed]
- Total Number of Donors and Cord Blood Units. Available online: https://statistics.wmda.info/ (accessed on 8 November 2023).
- Bruce Denniston Bone Marrow Sociey. Available online: https://www.dennistonsociety.org/ (accessed on 8 November 2023).
- Statistics Canada Table 98-10-0351-01 Visible Minority by Gender and Age: Canada, Provinces and Territories. 2021. Available online: https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=9810035101 (accessed on 4 April 2024).
- The Canadian Census: A Rich Portrait of the Country’s Religious and Ethnocultural Diversity. 2023. Available online: https://www150.statcan.gc.ca/n1/daily-quotidien/221026/dq221026b-eng.htm (accessed on 4 April 2024).
- Parmar, G.; Green, M.; Mostert, K.; Lawless, T.; Dibdin, N.; Weiss, J.; Ganz, K.; Petraszko, T.; Seftel, M.D.; Allan, D.S. A Portrait of Cord Blood Units Distributed for Transplantation from Canadian Blood Services’ Cord Blood Bank: First Analysis. Curr. Oncol. 2022, 29, 9572–9581. [Google Scholar] [CrossRef] [PubMed]
Ethnicity (Self-Reported) | Stem Cell Registry (%) | Cord Blood Bank (%) |
---|---|---|
White | 65.9 | 36.6 |
South and Southeast Asian | 9.9 | 22.3 |
Chinese | 7.1 | 3.6 |
Multiple ethnicity | 4.1 | 26.0 |
Black * | 1.7 | 5.3 |
Arab | 1.6 | 3.6 |
First Nations, Metis, Inuit | 1.5 | 0.4 |
Hispanic | 1.1 | 1.2 |
Other/Unknown | 8.6 | 1.2 |
TOTAL | 100.0 | 100.0 |
Ethnicity (Self-Reported) | 2018 SCR Proportion (%) | 2023 SCR Proportion (%) | 5-Year Delta (% Change) | 2021 Census (%) | 2021 Patient Searches (%) |
---|---|---|---|---|---|
White | 68.3 | 65.9 | −2.4 (−3.5) | 70.0 | 76.1 |
Black | 1.46 | 1.66 | +0.2 (+13.7) | 3.5 | 3.4 |
Chinese | 7.18 | 7.14 | −0.04 (−0.6) | 4.7 | 6.6 |
South Asian | 6.14 | 7.04 | +0.90 (+14.7) | 7.1 | 10.0 |
Indigenous | 1.31 | 1.51 | +0.20 (+15.2) | 5.0 | 2.8 |
Donor Age, n (%) | Total Donors, n = 291 |
---|---|
18–25 | 117 (40.2) |
26–35 | 133 (45.7) |
36–45 | 33 (11.3) |
46–55 | 6 (2.1) |
55–65 | 2 (0.7) |
Median | 27 |
Mean ± SEM | 28.4 ± 0.4 |
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Parmar, G.; Seftel, M.D.; Ganz, K.; Blake, J.; Holovati, J.L.; Allan, D.S. Optimizing Access to Unrelated Donors in Canada: Re-Examining the Importance of Donor Factors on Outcomes Following Hematopoietic Cell Transplantation. Curr. Oncol. 2024, 31, 2542-2551. https://doi.org/10.3390/curroncol31050190
Parmar G, Seftel MD, Ganz K, Blake J, Holovati JL, Allan DS. Optimizing Access to Unrelated Donors in Canada: Re-Examining the Importance of Donor Factors on Outcomes Following Hematopoietic Cell Transplantation. Current Oncology. 2024; 31(5):2542-2551. https://doi.org/10.3390/curroncol31050190
Chicago/Turabian StyleParmar, Gaganvir, Matthew D. Seftel, Kathy Ganz, John Blake, Jelena L. Holovati, and David S. Allan. 2024. "Optimizing Access to Unrelated Donors in Canada: Re-Examining the Importance of Donor Factors on Outcomes Following Hematopoietic Cell Transplantation" Current Oncology 31, no. 5: 2542-2551. https://doi.org/10.3390/curroncol31050190
APA StyleParmar, G., Seftel, M. D., Ganz, K., Blake, J., Holovati, J. L., & Allan, D. S. (2024). Optimizing Access to Unrelated Donors in Canada: Re-Examining the Importance of Donor Factors on Outcomes Following Hematopoietic Cell Transplantation. Current Oncology, 31(5), 2542-2551. https://doi.org/10.3390/curroncol31050190