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A low thymic function is associated with leukemia relapse in children given T-cell-depleted HLA-haploidentical stem cell transplantation

Leukemia volume 26, pages 1886–1888 (2012)Cite this article

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Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) provides an effective treatment for many malignant and non-malignant diseases in children. Unfortunately, <30% of patients who could benefit from an allograft have an HLA-identical related donor and the availability of an HLA-matched unrelated donor is markedly dependent on the ethnic origin of the patient. Thus, alternative sources of donors/stem cells, such as HLA-haploidentical (Haplo) family donors, are increasingly used.1 Although protocols of profound T-cell depletion and infusion of high doses of CD34+ cells permit to reach engraftment without graft-versus-host disease in the vast majority of Haplo-HSCT recipients,2 these patients experience a significant delay in immune reconstitution, leading to a high incidence of opportunistic infections.3 The absence of the T-cell-mediated graft-versus-leukemia (GVL) effect has also been thought to render the recipients of a T-cell-depleted allograft from an HLA-Haplo relative more susceptible to leukemia relapse. However, fundamental studies on Haplo-HSCT showed that a potent GVL effect could be mediated by natural killer (NK) cells when an HLA-disparate, NK-alloreactive relative was employed as a donor.4 Although some reports indicated an association between poor clinical outcome and low lymphocyte counts early after Haplo-HSCT,5 there is no study directly addressing the impact of T-cell reconstitution on relapse in longitudinal cohorts of pediatric patients having received this type of allograft. This issue is particularly relevant as the development of a potent immunity towards newly encountered antigens, including many of the known tumor antigens, requires thymic generation of naïve T cells with a broad specificity.6 In view of these considerations, we decided to investigate the recovery of thymic function in 33 patients given Haplo-HSCT, including 27 treated for hematological malignancies, using signal joint (sj) and beta T-cell receptor excision circles (TRECs).7, 8 These tools have already shown to be able to provide useful information in studies addressing the issues of aging, HIV infection and HSCT9 but not yet in the context of the risk of leukemia relapse after HSCT.

All patients had been transplanted with CD34+-selected cells after having received a fully myeloablative conditioning regimen between October 2004 and February 2007 at the Fondazione IRCCS Policlinico San Matteo in Pavia, Italy. Details on patient and donor characteristics, as well as on transplantation outcome, are reported in Table 1. No patient received post-transplantation pharmacological immune suppression. The study was approved by the Ethical Committee of Fondazione IRCCS Policlinico San Matteo (approval number 446/DG).

Table 1 Patient, donor characteristics and transplant outcomes
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Acknowledgements

This work was supported by research grants from AIRC (Associazione Italiana Ricerca sul Cancro, special grant 5 per 1000) to FL, Cancéropôle Ile-de-France and AP-HP ‘contrat de recherche translationelle en biologie 2010’ no. RTB1002. We would like to thank Rita Maccario for her helpful contribution.

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Author notes

  1. A Toubert and F Locatelli: These two authors contributed equally to this work.

Authors and Affiliations

  1. Departement d,

    E Clave, C Douay, M Busson, D Charron & A Toubert

  2. ′,

    E Clave, C Douay, M Busson, D Charron & A Toubert

  3. Immunologie, Université Paris Diderot, INSERM UMRS-940, AP-HP, Paris, France

    E Clave, C Douay, M Busson, D Charron & A Toubert

  4. Université Paris Diderot, Sorbonne Paris Cité, Paris, France

    E Clave, C Douay, M Busson, D Charron & A Toubert

  5. Pediatric Hematology–Oncology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

    D Lisini, G Giorgiani & M Zecca

  6. Hôpital Saint-Louis,

    D Charron & A Toubert

  7. , AP-HP, Paris, France

    D Charron & A Toubert

  8. Department of Pediatric Hematology and Oncology, University of Pavia, IRCCS Ospedale Bambino Gesù, Rome, Italy

    M E Bernardo & F Locatelli

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  1. E Clave
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  10. F Locatelli
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Correspondence to E Clave.

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Clave, E., Lisini, D., Douay, C. et al. A low thymic function is associated with leukemia relapse in children given T-cell-depleted HLA-haploidentical stem cell transplantation. Leukemia 26, 1886–1888 (2012). https://doi.org/10.1038/leu.2012.59

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