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Haploidentical transplantation with post-transplant cyclophosphamide following reduced-intensity conditioning for osteopetrosis: outcomes in three children

Bone Marrow Transplantation volume 51, pages 1546–1548 (2016)Cite this article

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Malignant infantile osteopetrosis (MIOP) is a heterogeneous group of severe disorders characterized by abnormal osteoclast activity. In untreated disease, children typically suffer severe bony abnormalities, hematopoietic failure, cranial neuropathies and death within the first decade.1 Allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for MIOP, and outcomes following HLA-matched related-donor (MRD) transplant are favorable. In sharp contrast, alternative-donor transplant for MIOP remains plagued by graft failure, regimen-related toxicity and poor overall survival.2, 3 Related, HLA-haploidentical donor HSCT has again emerged as a promising alternative-donor treatment strategy for patients with hematologic malignancies. Previous iterations of ‘haplo-transplant’ have generally failed to unify the desired transplant outcomes, including robust donor engraftment, low rates of GvHD and timely immune reconstitution. However, a T-cell replete, non-myeloablative regimen utilizing post-graft infusion high-dose cyclophosphamide (Haplo-post-transplant cyclophosphamide (PTCy)) has demonstrated efficacy approaching that following MRD HSCT.4 In addition, emerging reports chronicle success using the Haplo-PTCy platform for aplastic anemia and hemoglobinopathies.5, 6, 7 We hypothesized that the Haplo-PTCy strategy following reduced-intensity conditioning would achieve long-term engrafted survival for children in need of alternative-donor transplantation for MIOP, a disease in which donor carrier status does not impact the efficacy of transplantation.

Three consecutive children with MIOP, all with recessive TCIRG1 genotypes, presented to our institution without HLA-matched sibling donors and were treated by the Haplo-PTCy strategy in 2014–2015. In all patients, MIOP diagnosis was prompted when abnormal bone mineralization was incidentally seen on imaging for infectious concerns. Severe OP phenotype was evidenced in all children by bone marrow failure requiring transfusion of platelets and/or RBCs. All patients were <1 year old at the time of transplant. All underwent induction within 2 months of their diagnoses. Additional patient characteristics can be seen in Table 1.

Table 1 Patient, disease, and transplant characteristics and outcomes
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Authors and Affiliations

  1. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    T L Bahr

  2. Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA

    T Lund, N M Sando, P J Orchard & W P Miller

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  1. T L Bahr
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Bahr, T., Lund, T., Sando, N. et al. Haploidentical transplantation with post-transplant cyclophosphamide following reduced-intensity conditioning for osteopetrosis: outcomes in three children. Bone Marrow Transplant 51, 1546–1548 (2016). https://doi.org/10.1038/bmt.2016.180

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