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Review
. 2022 Jan 21:9:758680.
doi: 10.3389/fped.2021.758680. eCollection 2021.

HLA-Haploidentical Family Donors: The New Promise for Childhood Acute Lymphoblastic Leukaemia?

Syaza Ab Rahman  1 , Toni Matic  2 , Maya Yordanova  3 , Hany Ariffin  1
Affiliations
Review

HLA-Haploidentical Family Donors: The New Promise for Childhood Acute Lymphoblastic Leukaemia?

Syaza Ab Rahman et al. Front Pediatr. .

Abstract

Allogeneic haematopoietic stem cell transplantation (HSCT) is indicated in children with high-risk, relapsed or refractory acute lymphoblastic leukaemia (ALL). HLA-matched grafts from cord blood and stem cell repositories have allowed patients without suitable sibling donors to undergo HSCT. However, challenges in procuring matched unrelated donor (MUD) grafts due to high cost, ethnic disparity and time constraints have led to the exponential rise in the use of stem cells from human leukocyte antigen (HLA)-haploidentical family donors. Whilst HLA-haploidentical HSCT (hHSCT) performed in adult patients with acute leukaemia has produced outcomes similar to MUD transplants, experience in children is limited. Over the last 5 years, more data have emerged on hHSCT in the childhood ALL setting, allowing comparisons with matched donor transplants. The feasibility of hHSCT using adult family donors in childhood ALL may also address the ethical issues related to selection of minor siblings in matched sibling donor transplants. Here, we review hHSCT in paediatric recipients with ALL and highlight the emergence of hHSCT as a promising therapeutic option for patients lacking a suitable matched donor. Recent issues related to conditioning regimens, donor selection and graft-vs.-host disease prophylaxis are discussed. We also identify areas for future research to address transplant-related complications and improve post-transplant disease-free survival.

Keywords: acute lymphoblastic leukaemia (ALL); haematopoietic stem cell transplantation; haploidentical; human leukocyte antigen; paediatric.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared consortium with several of the authors HA and TM at time of review.

Figures

Figure 1
Figure 1
Donor-recipient immunocellular therapy to mitigate risk of leukaemia relapse. (A) Donor-derived T cells are selected and undergo modification or engineering to produce clonally expanded T cells of a specified subset e.g., regulatory T cells, CAR-T cells or T cells with externally inducible safety switch (B) adoptive transfer of modified T cells to the recipient. Image created with BioRender.com. CAR, chimeric antigen receptor.
See this image and copyright information in PMC

References

    1. Dalle JH, Balduzzi A, Bader P, Pieczonka A, Yaniv I, Lankester A, et al. . The impact of donor type on the outcome of pediatric patients with very high risk acute lymphoblastic leukemia. A study of the ALL SCT 2003 BFM-SG and 2007-BFM-International SG. Bone Marrow Transplant. (2021) 56:257–66. 10.1038/s41409-020-01014-x - DOI - PMC - PubMed
    1. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A, et al. . Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet. (2007) 369:1947–54. 10.1016/S0140-6736(07)60915-5 - DOI - PubMed
    1. Rocha V, Locatelli F. Searching for alternative hematopoietic stem cell donors for pediatric patients. Bone Marrow Transplant. (2008) 41:207–14. 10.1038/sj.bmt.1705963 - DOI - PubMed
    1. Smith AR, Wagner JE. Alternative haematopoietic stem cell sources for transplantation: place of umbilical cord blood. Br J Haematol. (2009) 147:246–61. 10.1111/j.1365-2141.2009.07828.x - DOI - PMC - PubMed
    1. Passweg JR, Baldomero H, Chabannon C, Basak GW, Corbacioglu S, Duarte R, et al. . The EBMT activity survey on hematopoietic-cell transplantation and cellular therapy 2018: CAR-T's come into focus. Bone Marrow Transplant. (2020) 55:1604–13. 10.1038/s41409-020-0826-4 - DOI - PMC - PubMed