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Improved survival and graft function in ex vivo T-cell depleted haploidentical hematopoietic cell transplantation for primary immunodeficiency

Bone Marrow Transplantation volume 56, pages 1200–1204 (2021)Cite this article

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A Correction to this article was published on 11 March 2021

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Hematopoietic cell transplantation (HCT) is a successful curative treatment for an increasing number of primary immunodeficiencies (PID). Despite an increased availability of potential matched donors worldwide including the use of banked cord bloods, there are a large number of patients for whom no matched donor can be found. Various techniques for T-cell depleting (TCD) mismatched donors have been used over the years to minimize the risks of graft rejection and graft versus host disease (GvHD). This retrospective study compared the outcomes according to TCD methods in 115 children with PID from January 1987 to December 2019. Thirteen patients who received additional gene-modified add-back T-cells were excluded. Fourteen patients who received TCR αβ/CD19 depleted mismatched grafts were previously reported by Shah et al. [1]. Outcomes of interest were: overall survival (OS), event-free survival (EFS), GvHD, CD3+ lymphocyte count at 3 months post-HCT, and latest donor chimerism. OS was defined as survival from first HCT to last follow-up or death. An event was defined as death, graft failure or second procedure for slipping chimerism. Subgroup differences in OS and EFS were evaluated by log-rank test. The difference in CD3+ lymphocyte count and donor chimerism between TCD methods was assessed by the Kruskal Wallis test.

A detailed description of transplant characteristics and outcomes is summarized in Table 1. The indication for an ex-vivo T-cell depleted graft has changed from predominantly severe combined immunodeficiency (SCID) to non-SCID PID between 1987 and 2019. The majority of ex-vivo T-cell depletions were performed in haploidentical parental donors (n = 98/115, 85%). Parents (45/47, 96%) were the main donors for CD3/CD19 depletion and TCR αβ/CD19 depletion. Two patients received a TCR αβ/CD19 depleted mismatched unrelated donor (MMUD) due to unsuitability of their parents. Marrow was used for CAMPATH-1M depletion (n = 34) and CD34 selection (n = 34) while peripheral blood stem cells (PBSC) were used for CD3/CD19 (n = 7) and TCR αβ/CD19 (n = 40) depletions. Prior to 2009, various conditioning regimens were used with the majority (n = 59/63, 94%) undergoing conditioning with busulfan and cyclophosphamide. Serotherapy and GvHD prophylaxis were given according to the institutional guidelines at the time of HCT. From 2009, a myeloablative reduced toxicity conditioning (RTC) regimen of fludarabine, treosulfan, ATG (Grafalon®), and rituximab was used for SCID. Thiotepa was added for non-SCID PID. No GvHD prophylaxis was given since 2015 in patients who received grafts with a TCR αβ content of < 5 × 104/kg or unconditioned transplants for SCID (n = 4/12, 33%) due to severe co-morbidities.

Table 1 Patient and transplantation characteristics, and transplant outcomes according to ex vivo T-cell depletion methods (N = 115).
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Fig. 1: Transplant outcomes according to ex vivo T-cell depletion methods.

Change history

  • 27 November 2020

    In the original version of the Article the Y axis for Figure 1e was incorrectly labelled “CD15+ donor chimerism, %” instead of “T-lymphocyte donor chimerism, (%)”. This has now been corrected in both the PDF and HTML versions of the Article.

  • 11 March 2021

    A Correction to this paper has been published: https://doi.org/10.1038/s41409-020-01175-9

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Acknowledgements

We would like to thank all patients, their families, and the treating multidisciplinary team.

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Authors and Affiliations

  1. Children’s Haematopoietic Stem Cell Transplant Unit, Great North Children’s Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, UK

    Su Han Lum, Ali Sobh, Zohreh Nademi, Peter McNaughton, Sabeena Selvarajah, Angela Deyà-Martínez, Mario Abinun, Terry Flood, Andrew Cant, Sophie Hambleton, Andrew R. Gennery & Mary Slatter

  2. Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands

    Su Han Lum

  3. Newcastle Cellular Therapies Facility, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, UK

    Kay Carruthers

  4. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

    Zohreh Nademi, Mario Abinun, Andrew Cant, Sophie Hambleton, Andrew R. Gennery & Mary Slatter

  5. Blood Sciences, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, UK

    Helen Watson

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Contributions

SHL developed the concept of research, collected the data, performed the statistical analysis, interpreted the data and prepared the manuscript. MS contributed to the conceptualization of the research, interpretation of the data, manuscript writing, and critical review at every level of the research stages. AG, TF, KC, ZN, SH, AC, and MA critically reviewed the manuscript. AS, HW, PM, ADM, and SS collected the data and reviewed the manuscript.

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Correspondence to Su Han Lum.

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Lum, S.H., Sobh, A., Carruthers, K. et al. Improved survival and graft function in ex vivo T-cell depleted haploidentical hematopoietic cell transplantation for primary immunodeficiency. Bone Marrow Transplant 56, 1200–1204 (2021). https://doi.org/10.1038/s41409-020-01152-2

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