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Bone marrow transplantation for beta-thalassaemia major by an HLA-mismatched parent
1Department of Pediatrics, Nanfang Hospital, Guangzhou, China. chunfu@fimmu.edu.cn
Insights
A bone marrow transplant from a one-antigen-mismatched mother successfully treated beta-thalassaemia major in a child. This approach offers a viable alternative for patients, especially in regions with limited treatment access.
Area of Science:
- Hematology
- Pediatric Oncology
- Immunology
Background:
- Beta-thalassaemia major is a severe genetic blood disorder requiring lifelong transfusions.
- Conventional treatments are not always accessible, necessitating alternative therapeutic strategies.
- This case explores bone marrow transplantation as a potential cure.
Observation:
- A pediatric patient with beta-thalassaemia major received a transplant from a one-antigen-mismatched maternal donor.
- Conditioning involved total body irradiation, busulfan, cyclophosphamide, and anti-thymocyte globulin.
- The patient experienced acute graft-versus-host disease (GVHD) and several complications, including sepsis and heart failure.
Findings:
- Successful engraftment was achieved, leading to transfusion independence at 18 months post-transplant.
- The patient recovered from complications without long-term sequelae.
- High-dose anti-thymocyte globulin and a higher marrow cell dose may improve outcomes.
Implications:
- A one-antigen-mismatched family member can be a viable bone marrow donor for beta-thalassaemia major.
- This strategy presents an alternative treatment option in resource-limited settings.
- Optimized immunosuppression and cell dosing are crucial for successful transplantation and GVHD prevention.
Abstract:
A six-year-old boy was diagnosed with beta-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 x 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for beta-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD.