Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Haploidentical stem cell transplantation with post-transplant cyclophosphamide for osteopetrosis and other nonmalignant diseases

Bone Marrow Transplantation volume 56, pages 434–441 (2021)Cite this article

Subjects

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for a variety of nonmalignant disorders including osteopetrosis, bone marrow failures, and immune deficiencies. Haploidentical HSCT is a readily available option in the absence of a matched donor, but engraftment failure and other post-transplant complications are a concern. Post-transplant cyclophosphamide (PT-Cy) regimens are gaining popularity and recent reports show promising results. We report our experience with nine pediatric patients with nonmalignant diseases who were transplanted from a haploidentical donor with PT-Cy. From 2015 to 2019, nine children with nonmalignant diseases underwent haploidentical HSCT with PT-Cy, two as a second transplant and seven as primary grafts after upfront serotherapy and busulfan-based myeloablative conditioning. Patient’s diseases included osteopetrosis (n = 5), congenital amegakaryocytic thrombocytopenia (n = 2), hemophagocytic lymphohistiocytosis (n = 1), and Wiskott Aldrich syndrome (n = 1). Two patients failed to engraft following upfront PT-Cy transplants, one was salvaged with a second PT-Cy transplant, and the other with a CD34+ selected graft. None of the patients suffered from graft-versus-host disease. Three patients died from early posttransplant infectious complications and six patients are alive and well. In conclusion, haploidentical HSCT with PT-Cy is a feasible option for pediatric patients with nonmalignant diseases lacking a matched donor.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Steward CG. Hematopoietic stem cell transplantation for osteopetrosis. Pediatr Clin NAm. 2010;57:171–80.

    Article  Google Scholar 

  2. Alter BP. Inherited bone marrow failure syndromes: considerations pre- and posttransplant. Hematol Am Soc Hematol Educ Progr. 2017;2017:88–95.

    Article  Google Scholar 

  3. Gennery AR, Albert MH, Slatter MA, Lankester A. Hematopoietic stem cell transplantation for primary immunodeficiencies. Front Pediatr. 2019;7:445.

    Article  Google Scholar 

  4. Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371:339–48.

    Article  CAS  Google Scholar 

  5. Mussetti A, Greco R, Peccatori J, Corradini P. Post-transplant cyclophosphamide, a promising anti-graft versus host disease prophylaxis: where do we stand? Expert Rev Hematol. 2017;10:479–92.

    Article  CAS  Google Scholar 

  6. Neven B, Diana JS, Castelle M, Magnani A, Rosain J, Touzot F, et al. Haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide for primary immunodeficiencies and inherited disorders in children. Biol Blood Marrow Transplant. 2019;25:1363–73.

    Article  Google Scholar 

  7. Kurzay M, Hauck F, Schmid I, Wiebking V, Eichinger A, Jung E, et al. T-cell replete haploidentical bone marrow transplantation and post-transplant cyclophosphamide for patients with inborn errors. Haematologica. 2019;104:e478–82.

    Article  Google Scholar 

  8. Uppuluri R, Sivasankaran M, Patel S, Swaminathan VV, Ramanan KM, Ravichandran N, et al. Haploidentical stem cell transplantation with post-transplant cyclophosphamide for primary immune deficiency disorders in children: challenges and outcome from a Tertiary Care Center in South India. J Clin Immunol. 2019;39:182–7.

    Article  CAS  Google Scholar 

  9. Klein OR, Chen AR, Gamper C, Loeb D, Zambidis E, Llosa N, et al. Alternative-donor hematopoietic stem cell transplantation with post-transplantation cyclophosphamide for nonmalignant disorders. Biol Blood Marrow Transplant. 2016;22:895–901.

    Article  CAS  Google Scholar 

  10. Mallhi KK, Srikanthan MA, Baker KK, Frangoul HA, Torgerson TR, Petrovic A et al. HLA-haploidentical hematopoietic cell transplantation for treatment of non-malignant diseases using nonmyeloablative conditioning and post-transplant cyclophosphamide. Biol Blood Marrow Transplant. 2020. https://doi.org/10.1016/j.bbmt.2020.03.018.

  11. Adhikari J, Gyawali B, Sharma P, Bhatt VR. Outcomes of haploidentical transplant compared with matched donor allogeneic stem cell transplant. Future Oncol. 2017;13:935–44.

    Article  CAS  Google Scholar 

  12. Guilcher GMT, Shah R, Shenoy S. Principles of alemtuzumab immunoablation in hematopoietic cell transplantation for non-malignant diseases in children: a review. Pediatr Transplant. 2018; 22. https://doi.org/10.1111/petr.13142.

  13. Tolar J, Teitelbaum SL, Orchard PJ. Osteopetrosis. N Engl J Med. 2004;351:2839–49.

    Article  Google Scholar 

  14. Penna S, Capo V, Palagano E, Sobacchi C, Villa A. One disease, many genes: implications for the treatment of osteopetroses. Front Endocrinol. 2019;10:85.

    Article  Google Scholar 

  15. Shadur B, Zaidman I, NaserEddin A, Lokshin E, Hussein F, Oron HC, et al. Successful hematopoietic stem cell transplantation for osteopetrosis using reduced intensity conditioning. Pediatr Blood Cancer. 2018;65:e27010.

    Article  Google Scholar 

  16. Orchard PJ, Fasth AL, Le Rademacher J, He W, Boelens JJ, Horwitz EM, et al. Hematopoietic stem cell transplantation for infantile osteopetrosis. Blood. 2015;126:270–6.

    Article  CAS  Google Scholar 

  17. Schulz AS, Classen CF, Mihatsch WA, Sigl-Kraetzig M, Wiesneth M, Debatin K-M, et al. HLA-haploidentical blood progenitor cell transplantation in osteopetrosis. Blood. 2002;99:3458–60.

    Article  CAS  Google Scholar 

  18. Pronk CJ, Turkiewicz D, Vult von Steyern K, Ehinger M, Dykes J, Toporski J. Transplantation of haploidentical TcRab-depleted hematopoietic cells allows for optimal timing and sustained correction of the metabolic defect in children with infantile osteopetrosis. J Bone Min Res. 2017;32:82–5.

    Article  Google Scholar 

  19. Fernandes JF, Nichele S, Daudt LE, Tavares RB, Seber A, Kerbauy FR, et al. Transplantation of hematopoietic stem cells for primary immunodeficiencies in brazil: challenges in treating rare diseases in developing countries. J Clin Immunol. 2018;38:917–26.

    Article  Google Scholar 

  20. Bahr TL, Lund T, Sando NM, Orchard PJ, Miller WP. Haploidentical transplantation with post-transplant cyclophosphamide following reduced-intensity conditioning for osteopetrosis: outcomes in three children. Bone Marrow Transplant. 2016;51:1546–8.

    Article  CAS  Google Scholar 

  21. Ballmaier M, Germeshausen M. Congenital amegakaryocytic thrombocytopenia: clinical presentation, diagnosis, and treatment. Semin Thromb Hemost. 2011;37:673–81.

    Article  CAS  Google Scholar 

  22. Dalle J-H, Peffault de Latour R. Allogeneic hematopoietic stem cell transplantation for inherited bone marrow failure syndromes. Int J Hematol. 2016;103:373–9.

    Article  CAS  Google Scholar 

  23. Mahadeo KM, Tewari P, Parikh SH, Driscoll TA, Page K, Martin PL, et al. Durable engraftment and correction of hematological abnormalities in children with congenital amegakaryocytic thrombocytopenia following myeloablative umbilical cord blood transplantation. Pediatr Transplant. 2015;19:753–7.

    Article  CAS  Google Scholar 

  24. Canna S, Marsh RA. Pediatric hemophagocytic lymphohistiocytosis (HLH). Blood. 2020. https://doi.org/10.1182/blood.2019000936.

  25. Allen CE, Marsh R, Dawson P, Bollard CM, Shenoy S, Roehrs P, et al. Reduced-intensity conditioning for hematopoietic cell transplant for HLH and primary immune deficiencies. Blood. 2018;132:1438–51.

    Article  CAS  Google Scholar 

  26. Kohli S, Rastogi N, Nivargi S, Thakkar D, Katewa S, Yadav SP. Successful haploidentical stem cell transplant with posttransplant cyclophosphamide for hemophagocytic lymphohistiocytosis. J Pediatr Hematol Oncol. 2019;41:e158–60.

    Article  CAS  Google Scholar 

  27. Ngwube A, Hanson IC, Orange J, Rider NL, Seeborg F, Shearer W, et al. Outcomes after allogeneic transplant in patients with Wiskott-Aldrich syndrome. Biol Blood Marrow Transplant. 2018;24:537–41.

    Article  Google Scholar 

  28. Yue Y, Shi X, Song Z, Qin J, Li J, Feng S, et al. Posttransplant cyclophosphamide for haploidentical stem cell transplantation in children with Wiskott-Aldrich syndrome. Pediatr Blood Cancer. 2018;65:e27092.

    Article  Google Scholar 

Download references

Acknowledgements

We thank our patients and their families for putting their trust in our care and allowing us to publish this paper. We thank our departmental nursing and administrative staff for their devoted work. We also thank Professor Zeev Rotstein, director of Hadassah Medical Center, for his support of our department. Shadur B’s position is supported by the Australian Government Research Training Program Scholarship and Hadassah, Australia. This work was supported by the Deutsche Forschungsgemeinschaft (Discovery and Evaluation of new Combined Immunodeficiency Disease Entities (DECIDE); grant DFG WA 1597/4-2) and the ERA-Net ERARE Consortium EURO-CID.

Author information

Authors and Affiliations

  1. Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Ehud Even-Or, Adeeb NaserEddin, Yael Dinur Schejter, Bella Shadur, Irina Zaidman & Polina Stepensky

  2. Department of Immunology, Graduate Research School, Garvan Institute of Medical Research and University of New South Wales, Sydney, New South Wales, Australia

    Bella Shadur

Authors
  1. Ehud Even-Or
    View author publications

    Search author on:PubMed Google Scholar

  2. Adeeb NaserEddin
    View author publications

    Search author on:PubMed Google Scholar

  3. Yael Dinur Schejter
    View author publications

    Search author on:PubMed Google Scholar

  4. Bella Shadur
    View author publications

    Search author on:PubMed Google Scholar

  5. Irina Zaidman
    View author publications

    Search author on:PubMed Google Scholar

  6. Polina Stepensky
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Ehud Even-Or.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Even-Or, E., NaserEddin, A., Dinur Schejter, Y. et al. Haploidentical stem cell transplantation with post-transplant cyclophosphamide for osteopetrosis and other nonmalignant diseases. Bone Marrow Transplant 56, 434–441 (2021). https://doi.org/10.1038/s41409-020-01040-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41409-020-01040-9

This article is cited by

Search

Advanced search

Quick links