HLA-identical haematopoietic stem cell transplantation for acute leukaemia in children: less relapse with higher biologically effective dose of TBI

• Published in: Bone marrow transplantation (Basingstoke) Vol. 40; no. 4; pp. 319 - 327
• Main Authors: WILLEMZE, A. J, GESKUS, R. B, NOORDIJK, E. M, KAL, H. B, EGELER, R. M, VOSSEN, J. M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.08.2007
• Subjects: Acute leukemia; Adolescent; Age; AML1 protein; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biological effects; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Cancer in children; Care and treatment; Child; Child, Preschool; Children; Complications; Cyclophosphamide; Decontamination; Diagnosis; Dose-Response Relationship, Radiation; Evaluation; Female; Graft Survival; Graft vs Host Disease; Graft-versus-host reaction; Health aspects; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Histocompatibility antigen HLA; Histocompatibility antigens; Histocompatibility Testing; HLA histocompatibility antigens; Humans; Infant; Kaplan-Meier Estimate; Leukemia; Leukemia, Myeloid, Acute - therapy; Male; Medical sciences; Methods; Microflora; Patients; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prophylaxis; Recurrence; Remission; Retrospective Studies; Stem cell transplantation; Stem cells; Survival; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Conditioning - methods; Transplantation, Homologous; Transplants & implants; Whole-Body Irradiation - methods; Netherlands; Human; Immunopathology; HLA-System; Total body irradiation; Relapse; Hematology; Stem cell; Major histocompatibility system; stem cell transplantation; Hematopoietic cell; Homograft; Acute leukemia; Graft versus host reaction; acute leukaemia; Survival; children; Graft; TBI; Effective dose; Child; graft-versus-host disease
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1705729

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.