Original Article
Bone Marrow Transplantation (2007) 40, 319–327. doi:10.1038/sj.bmt.1705729; published online 18 June 2007
Pediatric Transplants
HLA-identical haematopoietic stem cell transplantation for acute leukaemia in children: less relapse with higher biologically effective dose of TBI
A J Willemze1, R B Geskus2,3, E M Noordijk4, H B Kal5, R M Egeler1 and J M Vossen1
- 1Division of Immunology, Hematology, Oncology and Bone Marrow Transplantation and Autoimmune Diseases, Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands
- 2Department of Medical Statistics and Bioinformatics, Leiden University, Leiden, The Netherlands
- 3Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands
- 4Division of Radiation Oncology, Department of Clinical Oncology, Leiden University Medical Centre, Leiden, The Netherlands
- 5Department of Radiotherapy, University Medical Centre, Utrecht, The Netherlands
Correspondence: Dr AJ Willemze, Division of Immunology, Hematology, Oncology and Bone Marrow Transplantation and Autoimmune Diseases, Department of Paediatrics, Leiden University Medical Centre, Albinusdreef 2, Leiden 2300RC, The Netherlands. E-mail: A.J.Willemze@lumc.nl
Received 29 August 2006; Revised 12 March 2007; Accepted 20 April 2007; Published online 18 June 2007.
Abstract
To examine relapse, survival and transplant-related complications in relationship to disease- and pre-treatment-related characteristics, we evaluated 132 children, who consecutively received an allogeneic HLA-identical SCT for acute leukaemia in our centre: ALL in first remission (n=24), ALL in second remission (n=53) and AML in first remission (n=55). The source of the stem cells was bone marrow in all but three cases. Most patients (89%) were pre-treated with cyclophosphamide and an age-related dose of TBI. Initially, GVHD prophylaxis consisted of long-course MTX only (n=24), later short-course MTX and CsA (n=102) was given. All patients were nursed in strictly protective isolation and received total gut decontamination to suppress their potentially pathogenic enteric microflora. The 5-year probability of overall survival was 63, 53 and 74% for ALL1, ALL2 and AML1, respectively (median follow-up: 10.6 years). The overall transplant-related mortality was 6%. The incidence of acute GVHD was 17%; 6% was grades II–IV. A higher total biologically effective TBI dose (BED) resulted in a decreased relapse frequency (P=0.034) and increased overall survival. AML patients with acute GVHD got no relapse (P=0.02); this was not the case in ALL patients. Fractionated TBI regimens with higher BED should be evaluated in prospective studies.
Keywords:
children, acute leukaemia, stem cell transplantation, graft-versus-host disease, survival, TBI
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