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HLA-haploidentical donor transplants with post-transplant cyclophosphamide in children with primary immune deficiency disorders

Bone Marrow Transplantation volume 57, pages 668–670 (2022)Cite this article

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Primary immunodeficiency (PID) is relatively common in the Kingdom of Saudi Arabia, mainly due to a high rate of consanguinity and interrelated marriages. Hematopoietic stem cell transplantation (HCT) is considered as the curative treatment option for patients with many PID’s [1]. Haploidentical HCT serves as a potentially curative treatment option for patients, who do not have fully matched HLA donor [2]. A high rate of graft failure (about 60%) in pediatric patients with PID transplanted at our institution using cord blood (unpublished data) led us to explore alternative donor approach for better outcome. We are reporting preliminary results on our experience of HCT in pediatric PID patients using haploidentical donor with post-transplantation cyclophosphamide (PT/CY) in PID.

Eleven transplant naïve patients with PID underwent consecutive HCT between June 2017 and August 2018 using a haploidentical donor at our institution. We used an established institutional protocol comprising of Thiotepa 5 mg/kg per dose on days −6 and −5, Fludarabine 50 mg/m2 per dose on days −4, −3 and −2 (total dose 150 mg/m2), Busulfan, which was based on actual weight, on days −4,−3 and −2 and Antithymocyte globulins (Fresenius, ATG) 5 mg/kg on days −6,−5 and −4 as conditioning regimen [3]. Graft versus host disease (GvHD) prophylaxis included Cyclosporine and Mycophenolate mofetil (MMF) on day +6 and PT/CY 50 mg/kg on days +3 and +5. Mesna was given with each dose of cyclophosphamide. All patients received Filgrastim 5 mcg/kg/day from day +6 and until their absolute neutrophil count (ANC) was above 1000 ×106/L for three consecutive days. Anti-infectious prophylaxis included Acyclovir, Fluconazole and Trimethoprim-Sulfamethoxzole. Cytomegalovirus reactivation was monitored weekly until last follow-up.

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References

  1. Porta F, Forino C, De Martiis D, Soncini E, Notarangelo L, Tettoni K, et al. Stem cell transplantation for primary immunodeficiencies. Bone Marrow Transp. 2008;41(Suppl 2):S83–86. https://doi.org/10.1038/bmt.2008.61. e-pub ahead of print 2008/07/24.

    Article  Google Scholar 

  2. Castagnoli R, Delmonte OM, Calzoni E, Notarangelo LD. Hematopoietic stem cell transplantation in primary immunodeficiency diseases: current status and future perspectives. Front Pediatr. 2019;7:295. https://doi.org/10.3389/fped.2019.00295. e-pub ahead of print 2019/08/24.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Al-Seraihy A, Al-Saedi H, Al-Ahmari A, Ghemlas I, Ayas M T-cell replete haploidentical transplantation with reduced post-transplant cyclophosphamide in six children with infantile osteopetrosis. Bone Marrow Transpl. 2021. https://doi.org/10.1038/s41409-021-01282-1. e-pub ahead of print 2021/04/08.

  4. Luznik L, Fuchs EJ. High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation. Immunol Res. 2010;47:65–77. https://doi.org/10.1007/s12026-009-8139-0. e-pub ahead of print 2010/01/13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, et al. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol. 2013;31:1310–6. https://doi.org/10.1200/JCO.2012.44.3523. e-pub ahead of print 2013/02/21.

    Article  CAS  PubMed  Google Scholar 

  6. Munchel AT, Kasamon YL, Fuchs EJ. Treatment of hematological malignancies with nonmyeloablative, HLA-haploidentical bone marrow transplantation and high dose, post-transplantation cyclophosphamide. Best Pr Res Clin Haematol. 2011;24:359–68. https://doi.org/10.1016/j.beha.2011.05.001. e-pub ahead of print 2011/09/20.

    Article  CAS  Google Scholar 

  7. 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 Transpl. 2019;25:1363–73. https://doi.org/10.1016/j.bbmt.2019.03.009. e-pub ahead of print 2019/03/17.

    Article  Google Scholar 

  8. Abdelhakim H, Abdel-Azim H, Saad A Role of alphabeta T cell depletion in prevention of graft versus host disease. Biomedicines. 2017;5. https://doi.org/10.3390/biomedicines5030035. e-pub ahead of print 2017/07/05.

  9. 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. https://doi.org/10.1007/s10875-019-00600-z. e-pub ahead of print 2019/02/20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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 Transpl. 2016;22:895–901. https://doi.org/10.1016/j.bbmt.2016.02.001. e-pub ahead of print 2016/02/11.

    Article  CAS  Google Scholar 

  11. Even-Or E, NaserEddin A, Dinur Schejter Y, Shadur B, Zaidman I, Stepensky P. Haploidentical stem cell transplantation with post-transplant cyclophosphamide for osteopetrosis and other nonmalignant diseases. Bone Marrow Transpl. 2021;56:434–41. https://doi.org/10.1038/s41409-020-01040-9. e-pub ahead of print 2020/08/29.

    Article  CAS  Google Scholar 

  12. 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. https://doi.org/10.1002/pbc.27092. e-pub ahead of print 2018/05/11.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    Hawazen AlSaedi, Khawar Siddiqui, Ali Al-Ahmari, Abdullah Al-Jefri, Ibrahim Ghemlas, Awatif AlAnazi, Amal Al-Seraihy, Hassan El-Solh & Mouhab Ayas

  2. Department of Pediatrics King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    Reem Mohammed, Bandar AlSaud & Hamoud Almousa

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  1. Hawazen AlSaedi
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  4. Ali Al-Ahmari
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  7. Abdullah Al-Jefri
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  11. Hassan El-Solh
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  12. Mouhab Ayas
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Contributions

HAlS and AAlS conceived the study. HAlS and KS designed the research and acquired the data. KS served as the principal data analyst and wrote the results. HAlS, KS and MA prepared the manuscript and were responsible for all revisions. RM, AAl-A, BAlS, HA, AAl-J, IG, AAlA, AAl-S, HEl-S, and MA reviewed the results, the manuscript and performed the final approval of the manuscript.

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Correspondence to Hawazen AlSaedi.

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Competing interests

The authors declare no competing interests.

Ethical approval

This study was submitted to the Institutional Review Board and was approved by the Research Advisory Committee through established procedures with an approval number 2191193. Moreover, parents/guardians of all patients undergoing HCT agreed to, and signed an informed consent at the time of transplant which includes a statement on use of non-identifiable treatment and outcome related data of their patient for academic and research purposes.

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AlSaedi, H., Mohammed, R., Siddiqui, K. et al. HLA-haploidentical donor transplants with post-transplant cyclophosphamide in children with primary immune deficiency disorders. Bone Marrow Transplant 57, 668–670 (2022). https://doi.org/10.1038/s41409-022-01589-7

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