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B-cell reconstitution recapitulates B-cell lymphopoiesis following haploidentical BM transplantation and post-transplant CY

Bone Marrow Transplantation volume 50, pages 317–319 (2015)Cite this article

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The treatment of many hematological diseases benefits from myeloablative or non-myeloablative conditioning regimens followed by SCT or BMT. HLA-matched donors are preferred but not always available. Instead, haploidentical donors can be rapidly identified. Unmanipulated haploidentical BMT (haploBMT) with non-myeloablative conditioning and post-transplant Cy has been developed to provide a universal source of BM donors.1 Cy, which depletes proliferating/allogeneic cells, prevents GVHD.1 Importantly, the infection-related mortality was remarkably low, suggesting effective immune reconstitution.1, 2 However, a detailed analysis in this regard is missing. Here we show the dynamics of the B-cell compartment.

Ten consecutive patients were treated with the haploBMT protocol established by Luznik et al.1 (see Supplementary Methods for details; Supplementary Figure 1A). Patient characteristics are listed in Supplementary Table 1. Blood and BM were obtained from Humanitas Cancer Center. Peripheral blood (PB) and BM were processed and frozen in liquid nitrogen according to the standard procedures and prepared for flow cytometry, as described.3 Non-parametric Wilcoxon rank test was used to compare distributions. Differences in the pie chart distributions were calculated with SPICE software (National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA) by using a permutation test. P-values are two sided and were considered significant when ⩽0.05.

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Figure 2

References

  1. Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 2008; 14: 641–650.

    Article  CAS  Google Scholar 

  2. Raiola A, Dominietto A, Varaldo R, Ghiso A, Galaverna F, Bramanti S et al. Unmanipulated haploidentical BMT following non-myeloablative conditioning and post-transplantation CY for advanced Hodgkin's lymphoma. Bone Marrow Transplant 2014; 49: 190–194.

    Article  CAS  Google Scholar 

  3. Lugli E, Mueller YM, Lewis MG, Villinger F, Katsikis PD, Roederer M . IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques. Blood 2011; 118: 2520–2529.

    Article  CAS  Google Scholar 

  4. Cabatingan MS, Schmidt MR, Sen R, Woodland RT . Naive B lymphocytes undergo homeostatic proliferation in response to B cell deficit. J Immunol 2002; 169: 6795–6805.

    Article  CAS  Google Scholar 

  5. Lee J, Kuchen S, Fischer R, Chang S, Lipsky PE . Identification and characterization of a human CD5+ pre-naive B cell population. J Immunol 2009; 182: 4116–4126.

    Article  CAS  Google Scholar 

  6. Suryani S, Fulcher DA, Santner-Nanan B, Nanan R, Wong M, Shaw PJ et al. Differential expression of CD21 identifies developmentally and functionally distinct subsets of human transitional B cells. Blood 2010; 115: 519–529.

    Article  CAS  Google Scholar 

  7. Suryani S, Tangye SG . Therapeutic implications of advances in our understanding of transitional B-cell development in humans. Expert Rev Clin Immunol 2010; 6: 765–775.

    Article  Google Scholar 

  8. Sims GP, Ettinger R, Shirota Y, Yarboro CH, Illei GG, Lipsky PE . Identification and characterization of circulating human transitional B cells. Blood 2005; 105: 4390–4398.

    Article  CAS  Google Scholar 

  9. Palanichamy A, Barnard J, Zheng B, Owen T, Quach T, Wei C et al. Novel human transitional B cell populations revealed by B cell depletion therapy. J Immunol 2009; 182: 5982–5993.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank the patients for their participation to this study and the nurse team of the Hematology and Bone Marrow Transplant Unit (Humanitas Research Hospital, Rozzano, Milan, Italy) who performed blood draws and samples collection, Margaret Beddall and Pratip Chattopadhyay (Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA) for Ab conjugation and validation, Achille Anselmo and Chiara Buracchi (Flow Cytometric facility, Humanitas Clinical and Research Center) for help with cell sorting, Barbara Cassani and Gaetano Bulfamante (Unit of Pathology of San Paolo Hospital, Milan, Italy) for the chimerism analyses and Anna Villa (CNR, Milan, Italy) and the members of the Mavilio laboratory for critical discussion. This work has been supported by grants from the Fondazione Cariplo (Grant Ricerca Biomedica 2012/0683 to EL), by European Union (Marie Curie Career Integration Grant 322093 to EL), by Associazione Italiana per la Ricerca sul Cancro (AIRC) (MFAG 10607 to EL), by the intramural program of the National Institutes of Allergy and Infectious Diseases to MR and by intramural research and clinical funding programs assigned to DM and LC. Alessandra Roberto is a recipient of the ‘Guglielmina Lucatello e Gino Mazzega’ fellowship from the Fondazione Italiana per la Ricerca sul Cancro (FIRC). ClinicalTrials.gov identifier No. NCT02049424.

Author Contributions

AR planned and performed experiments, analyzed data and wrote the manuscript; LC, SG, SB, BS RC, ET, CCS and AS performed the clinical procedures and enrolled patients for this research proposal; VZ, performed experiments; PT and IT provided technical support with sample processing, SDB contributed to data analysis and manuscript writing; MR provided reagents and technical support and revised the manuscript; DM and EL conceived the study, interpreted data and wrote the manuscript.

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Author notes

  1. D Mavilio and E Lugli: These authors contributed equally to this work.

Authors and Affiliations

  1. Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Italy

    A Roberto, V Zanon, P Tentorio, S Della Bella, D Mavilio & E Lugli

  2. Hematology and Bone Marrow Transplant Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Italy

    L Castagna, S Gandolfi, S Bramanti, B Sarina, R Crocchiolo, E Todisco, C Carlo-Stella, I Timofeeva & A Santoro

  3. Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan, Milan, Italy

    S Della Bella & D Mavilio

  4. ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    M Roederer

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Corresponding authors

Correspondence to D Mavilio or E Lugli.

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Roberto, A., Castagna, L., Gandolfi, S. et al. B-cell reconstitution recapitulates B-cell lymphopoiesis following haploidentical BM transplantation and post-transplant CY. Bone Marrow Transplant 50, 317–319 (2015). https://doi.org/10.1038/bmt.2014.266

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