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T-cell replete haploidentical transplantation with reduced post-transplant cyclophosphamide in six children with infantile osteopetrosis

Bone Marrow Transplantation volume 56, pages 1757–1760 (2021)Cite this article

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Infantile osteopetrosis (OP) is a rare genetic disorder of osteoclast development and/or function. Hematopoietic cell transplantation (HCT) is the only curative approach for most children with OP. HCT in children with infantile OP is complicated by a high incidence of graft failure and increased transplant-related toxicity particularly when using alternative donors [1, 2]. In recent years, haploidentical T-cell replete HCT with high-dose post-transplant cyclophosphamide (Haplo-PTCy) has become a valid alternative transplant strategy for patients without HLA-matched donor with malignant and nonmalignant diseases [3, 4]. It is believed that infantile OP requires myeloablative conditioning to overcome graft failure but the use of Haplo-PTCy is associated with additional toxicity such as hemorrhagic cystitis and high-grade mucositis in patients who already suffer from failure to thrive and narrow airways, plus the increased risks of veno-occlusive disease (VOD) and pneumonitis [1, 2, 5]. We hypothesized that the Haplo-PTCy strategy with fludarabine-based myeloablative conditioning followed by reduced dose of post-transplant cyclophosphamide would achieve long-term engrafted survival for osteopetrosis with lower rate of regimen-related toxicities.

Six children with infantile OP presented to our institution without HLA-matched donors, between July 2016 and October 2019. The diagnosis of OP was based on molecular studies, skeletal radiologic changes, and extra-medullary hematopoiesis. Patients’ characteristics are summarized in Table 1. Median age at HCT was 10.6 months (range, 5–39 months). All patients underwent HCT within 2 months of their diagnosis except Patient 4 who received a second transplant after graft failure 1 year after her first cord transplant.

Table 1 Patient, disease, and transplant characteristics and outcomes.
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  1. Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    Amal Al-Seraihy, Hawazen Al-Saedi, Ali Al-Ahmari, Ibrahim Ghemlas & Mouhab Ayas

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  1. Amal Al-Seraihy
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  2. Hawazen Al-Saedi
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Correspondence to Amal Al-Seraihy.

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Al-Seraihy, A., Al-Saedi, H., Al-Ahmari, A. et al. T-cell replete haploidentical transplantation with reduced post-transplant cyclophosphamide in six children with infantile osteopetrosis. Bone Marrow Transplant 56, 1757–1760 (2021). https://doi.org/10.1038/s41409-021-01282-1

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