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Allogeneic bone marrow transplantation in Chédiak-Higashi syndrome
M Möttönen1, M Lanning, U M Saarinen
1Department of Pediatrics, University of Oulu, Finland.
Insights
Allogeneic bone marrow transplantation (BMT) offers a potential cure for Chédiak-Higashi syndrome (CHS). This case study shows successful BMT in a young boy, achieving mixed chimerism and long-term survival.
Area of Science:
- Hematology
- Immunology
- Genetics
Background:
- Chédiak-Higashi syndrome (CHS) is a rare genetic disorder characterized by impaired lysosomal trafficking.
- Patients with CHS experience recurrent infections and often present with an accelerated phase requiring urgent treatment.
- Traditional treatments have limited efficacy, highlighting the need for alternative therapeutic strategies.
Observation:
- A pediatric patient with CHS presented with recurrent bacterial infections and an accelerated phase.
- The patient underwent allogeneic bone marrow transplantation (BMT) from an HLA- and mixed leukocyte culture-identical sibling.
- The preparative regimen included busulfan and cyclophosphamide, with GVHD prophylaxis using methotrexate and cyclosporine A.
Findings:
- Successful engraftment was achieved post-BMT, with no acute graft-versus-host disease (GVHD).
- The patient reached a mixed chimerism state, with donor cells comprising approximately 50% of peripheral blood and bone marrow.
- Chédiak-Higashi granules were observed in neutrophils and myelopoietic cells, indicating successful BMT and partial correction of the cellular defect.
Implications:
- Allogeneic BMT is a potentially curative therapy for Chédiak-Higashi syndrome, even when resulting in mixed chimerism.
- This approach offers a viable treatment option for CHS patients refractory to conventional therapies.
- Long-term survival and improved quality of life are achievable following successful BMT for CHS.
Abstract:
A boy with Chédiak-Higashi syndrome (CHS) treated by allogeneic bone marrow transplantation (BMT) is described. He had had several respiratory infections during his first 2 years of life, and at the age of 2.5 years he presented with an accelerated phase of CHS. Despite treatment with ascorbic acid and trimethoprim/sulfamethoxazole, he continued to experience recurrent bacterial infections. Allogeneic BMT was performed with his HLA- and mixed leukocyte culture-identical healthy brother as the donor. The preparative regimen consisted of busulfan and cyclophosphamide, and methotrexate and cyclosporine A were given as prophylaxis for graft-versus-host disease (GVHD). The patient engrafted well, and no symptoms or signs of acute GVHD developed. He then achieved chimerism status, in which half the peripheral blood neutrophils and some of the bone marrow myelopoietic cells displayed Chédiak-Higashi granules, and DNA analysis showed half the peripheral blood cells to be of donor origin and the other half to be of host origin. The boy is currently alive and well 24 months after transplant. Allogeneic BMT, even with mixed chimerism as a result, is a potentially curative therapy for CHS.