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Thalassaemia

Paediatric allogeneic bone marrow transplantation for homozygous β-thalassaemia, the Dutch experience

Bone Marrow Transplantation volume 31, pages 1081–1087 (2003)Cite this article

Summary:

We reviewed the results of the Dutch paediatric bone marrow transplant (BMT) program for children receiving HLA-identical BMT for β-thalassaemia major over an 18-year period. In all, 19 patients underwent a total of 21 transplants in our treatment centre between July 1984 and February 2002. Eight females (age 0.3–12 years; median 5 years) and 11 males (age 0.8–18 years; median 6 years) were included. Information, prospectively collected, included molecular defects, donor genotype, β/α-globin expression rates, serum ferritin levels, hepato-splenomegaly, chelation history, virology screening, liver pathology together with post-transplant outcome inclusive of leucocyte chimerism. In total, 11 patients received standard busulphan/cyclophosphamide (Bu/Cy) conditioning, with or without ATG. Stable engraftment was seen in 5/11 with late rejection occurring in six patients. Of these, two children underwent a second successful SCT. For this group, overall event-free survival (EFS) and disease-free survival (DFS) were 90 (10/11) and 64% (7/11), respectively. The probability of rejection was 55%. Subsequent addition of melphalan to the conditioning regimen resulted in long-term stable engraftment in all patients with an EFS/DFS for this group of 90% (9/10). Treatment-related mortality, irrespective of conditioning, was low at 5% (1/19 patients). Veno-occlusive disease (VOD) occurred in 19% (4/21 transplants) and acute GvHD in 19% (4/21 transplants). Post-BMT β/α synthetic ratio measurement monitored donor erythroid engraftment and predicted rejection with a return to transfusion dependency. Maintained full donor chimerism is indicative of stable engraftment both for leucocyte and erythroid lineages, whereas mixed donor chimerism is not. Our results emphasise the importance of the conditioning regimen and post-transplant chimerism surveillance predictive of rejection or long-term stable engraftment.

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Acknowledgements

We thank the medical, nursing and ancillary staff of the IHOBA unit together with Mrs H. Bakker, data manager, Department of Paediatrics, LUMC and the staff of the Europdonor, Leiden, The Netherlands, for their help in the management of patients undergoing bone marrow transplantation. We thank Dr M.J.D van Tol of the Paediatric Immunology Laboratory, LUMC and Dr J Wijnen of the Sylvius Laboratory, Leiden for XY FISH and VNTR analysis, respectively.

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  1. The Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands

    L M Ball, A C Lankester, M H van Weel, R G M Bredius, F J Smiers, R M Egeler & J M J J Vossen

  2. Department of Human and Clinical Genetics, The Haemoglobinopathies Laboratory, Leiden University Medical Centre, Leiden, The Netherlands

    P C Giordano & C L Harteveld

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Ball, L., Lankester, A., Giordano, P. et al. Paediatric allogeneic bone marrow transplantation for homozygous β-thalassaemia, the Dutch experience. Bone Marrow Transplant 31, 1081–1087 (2003). https://doi.org/10.1038/sj.bmt.1704066

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