Donor Age and Non-Relapse Mortality: Study of Their Association After HLA-Matched Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Overview

Journal Curr Oncol

Publisher MDPI

Specialty Oncology

Date 2022 Aug 25

PMID 36005208

Authors

Yasmine Kadri

Michelle Phan

Nadia Bambace

Lea Bernard

Sandra Cohen

Jean-Sebastien Delisle

Thomas Kiss

Sylvie Lachance

Denis-Claude Roy

Guy Sauvageau

Olivier Veilleux

Jean Roy

Imran Ahmad

Affiliations

Soon will be listed here.

Abstract

The purpose of this retrospective study was to study the correlation between donor age (DA) and non-relapse mortality (NRM) and relapse incidence (RI) among patients treated with allogeneic hematopoietic cell transplantation (aHCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in a single Canadian center. Data from 125 consecutive patients transplanted with a matched related or unrelated donor between 2015 and 2020 were analyzed using multivariable models. After a median follow-up of 2.8 years, the cumulative incidences of NRM and relapse were 19% and 35% at 5 years. Despite being independently associated with NRM and relapse-free survival (RFS), DA was not associated with RI. The independent determinants of NRM in addition to DA were patient age and hematopoietic cell transplantation comorbidity index (HCT-CI), independently of donor kinship. The effect of DA on NRM was found to be significantly increased over the age of 50 years. DA was not associated with incidence of acute graft-versus-host disease (aGVHD) but showed an association with the occurrence of chronic GVHD (cGVHD). In conclusion, younger donors should be favored to limit NRM and increase RFS in HLA-matched aHCT. The etiological mechanisms behind the association of DA with higher NRM remain to be elucidated.

References

Ciurea S, Al Malki M, Kongtim P, Fuchs E, Luznik L, Huang X . The European Society for Blood and Marrow Transplantation (EBMT) consensus recommendations for donor selection in haploidentical hematopoietic cell transplantation. Bone Marrow Transplant. 2019; 55(1):12-24. DOI: 10.1038/s41409-019-0499-z. View

Guru Murthy G, Kim S, Hu Z, Estrada-Merly N, Abid M, Aljurf M . Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors. JAMA Oncol. 2022; 8(3):404-411. PMC: 8759031. DOI: 10.1001/jamaoncol.2021.6846. View

Kollman C, HOWE C, Anasetti C, Antin J, Davies S, Filipovich A . Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood. 2001; 98(7):2043-51. DOI: 10.1182/blood.v98.7.2043. View

Atkinson K, Farrell C, Chapman G, Downs K, Penny R, Biggs J . Female marrow donors increase the risk of acute graft-versus-host disease: effect of donor age and parity and analysis of cell subpopulations in the donor marrow inoculum. Br J Haematol. 1986; 63(2):231-9. DOI: 10.1111/j.1365-2141.1986.tb05545.x. View

Mehta J, Gordon L, Tallman M, Winter J, Evens A, Evens A . Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially?. Bone Marrow Transplant. 2006; 38(2):95-100. DOI: 10.1038/sj.bmt.1705388. View

Flowers M, Inamoto Y, Carpenter P, Lee S, Kiem H, Petersdorf E . Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011; 117(11):3214-9. PMC: 3062319. DOI: 10.1182/blood-2010-08-302109. View

Carreras E, Jimenez M, Gomez-Garcia V, de la Camara R, Martin C, Martinez F . Donor age and degree of HLA matching have a major impact on the outcome of unrelated donor haematopoietic cell transplantation for chronic myeloid leukaemia. Bone Marrow Transplant. 2005; 37(1):33-40. DOI: 10.1038/sj.bmt.1705195. View

Richa E, Kunnavakkam R, Godley L, Kline J, Odenike O, Larson R . Influence of related donor age on outcomes after peripheral blood stem cell transplantation. Cytotherapy. 2012; 14(6):707-15. DOI: 10.3109/14653249.2012.681041. View

Penack O, Peczynski C, Mohty M, Yakoub-Agha I, Styczynski J, Montoto S . How much has allogeneic stem cell transplant-related mortality improved since the 1980s? A retrospective analysis from the EBMT. Blood Adv. 2020; 4(24):6283-6290. PMC: 7756984. DOI: 10.1182/bloodadvances.2020003418. View

10.

Shouval R, Fein J, Labopin M, Cho C, Bazarbachi A, Baron F . Development and validation of a disease risk stratification system for patients with haematological malignancies: a retrospective cohort study of the European Society for Blood and Marrow Transplantation registry. Lancet Haematol. 2021; 8(3):e205-e215. PMC: 9190021. DOI: 10.1016/S2352-3026(20)30394-X. View

11.

Azuma E, Hirayama M, Yamamoto H, Komada Y . The role of donor age in naive T-cell recovery following allogeneic hematopoietic stem cell transplantation: the younger the better. Leuk Lymphoma. 2002; 43(4):735-9. DOI: 10.1080/10428190290016827. View

12.

Passweg J, Baldomero H, Chabannon C, Basak G, de la Camara R, Corbacioglu S . Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years. Bone Marrow Transplant. 2021; 56(7):1651-1664. PMC: 8263343. DOI: 10.1038/s41409-021-01227-8. View

13.

Kroger N, Zabelina T, de Wreede L, Berger J, Alchalby H, van Biezen A . Allogeneic stem cell transplantation for older advanced MDS patients: improved survival with young unrelated donor in comparison with HLA-identical siblings. Leukemia. 2012; 27(3):604-9. DOI: 10.1038/leu.2012.210. View

14.

McDonald G, Sandmaier B, Mielcarek M, Sorror M, Pergam S, Cheng G . Survival, Nonrelapse Mortality, and Relapse-Related Mortality After Allogeneic Hematopoietic Cell Transplantation: Comparing 2003-2007 Versus 2013-2017 Cohorts. Ann Intern Med. 2020; 172(4):229-239. PMC: 7847247. DOI: 10.7326/M19-2936. View

15.

Bastida J, Cabrero M, Lopez-Godino O, Lopez-Parra M, Sanchez-Guijo F, Lopez-Corral L . Influence of donor age in allogeneic stem cell transplant outcome in acute myeloid leukemia and myelodisplastic syndrome. Leuk Res. 2015; 39(8):828-34. DOI: 10.1016/j.leukres.2015.05.003. View

16.

DSouza A, Fretham C, Lee S, Arora M, Brunner J, Chhabra S . Current Use of and Trends in Hematopoietic Cell Transplantation in the United States. Biol Blood Marrow Transplant. 2020; 26(8):e177-e182. PMC: 7404814. DOI: 10.1016/j.bbmt.2020.04.013. View

17.

Rezvani A, Storer B, Guthrie K, Schoch H, Maloney D, Sandmaier B . Impact of donor age on outcome after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014; 21(1):105-12. PMC: 4286386. DOI: 10.1016/j.bbmt.2014.09.021. View

18.

Kollman C, Spellman S, Zhang M, Hassebroek A, Anasetti C, Antin J . The effect of donor characteristics on survival after unrelated donor transplantation for hematologic malignancy. Blood. 2015; 127(2):260-7. PMC: 4713163. DOI: 10.1182/blood-2015-08-663823. View

19.

Lin R, Artz A . Allogeneic hematopoietic cell transplantation for older patients. Hematology Am Soc Hematol Educ Program. 2021; 2021(1):254-263. PMC: 8791130. DOI: 10.1182/hematology.2021000257. View

20.

Hirayama M, Azuma E, Jiang Q, Kobayashi M, Iwamoto S, Kumamoto T . The reconstitution of CD45RBhiCD4+ naive T cells is inversely correlated with donor age in murine allogeneic haematopoietic stem cell transplantation. Br J Haematol. 2000; 111(2):700-7. DOI: 10.1046/j.1365-2141.2000.02391.x. View