To investigate if children who later developed acute lymphoblastic leukaemia (ALL) were prenatally infected with HHV-6 and/or EBV, Guthrie cards taken at birth were analysed by PCR. Guthrie cards from 54 patients with ALL and 47 healthy controls matched for age and birth place were tested negative for both HHV-6 and EBV DNA. All samples contained amplifiable DNA when tested by HLA-DQ PCR. Our negative findings suggest that childhood ALL is unlikely to be associated with an in utero infection with EBV or HHV-6.

Summary:To examine whether graft-versus-host-disease (GVHD) is associated with a graft-versus-leukaemia (GVL) effect that also influences the outcome of allogeneic stem cell transplantation (SCT) in childhood acute leukaemia, we evaluated all consecutive (n ¼ 169) children who had undergone SCT for ALL and AML at our centre. Median followup was 7 years. The 5-year probability of chronic GVHD was 34%. Median time to relapse was 24 months in children with chronic GVHD and 6 months in those without. The corresponding 5-year probabilities of relapse were 30 and 45% (P ¼ 0.01). The 5-year probability of survival was 54%. Patients with chronic GVHD had a significantly better survival, 77 vs 51% (P ¼ 0.01). In a Cox regression model, chronic GVHD independently decreased the risk of relapse (RR 0.44) and further predicted an increased chance of relapse-free survival (RR 1.7) and survival (RR 2.6). The impact of chronic GVHD on survival was most apparent in late-stage disease and in ALL. Acute GVHD was not an independent predictor for relapse or death in this study. This study is in support of a GVL effect in childhood leukaemia related to chronic GVHD, reducing the risk of relapse and improving survival. Bone Marrow Transplantation (2003) 31, 175-181. doi:10.1038/sj.bmt.1703808 Keywords: bone marrow transplantation; children graft-versus-host disease; graft-versus-leukaemia; relapse survivalThe major cause of failure after haematopoietic stem cell transplantation (SCT) in childhood leukaemia is relapse of disease, followed by transplant-related causes such as graftversus-host disease (GVHD), treatment toxicity and infections. 1,2 The original concept of SCT was to enable complete eradication of malignant cells by a maximum dose of chemoradiotherapy, bypassing the otherwise dose-limiting bone marrow aplasia with a salvaging autologous or allogeneic graft. In addition, now a well-established belief in the immunotherapeuthic potential of the allogeneic graft has evolved, usually described as the graft-versus-leukaemia (GVL) effect. This antileukaemia effect was first postulated in the 1950s by Barnes 3 and later reported in humans by Weiden et al 4 in 1979. Acute and chronic GVHD were presented as favourable in decreasing the risk of relapse.This was later confirmed in an IBMTR study in 1990, 5 which further supported the existence of a GVL effect by reporting a higher probability of relapse in patients receiving T-cell-depleted (TCD) or syngeneic grafts. Several recent studies, including those on the effect of donor lymphocyte infusions (DLI), have strengthened this concept. [6][7][8][9] However, treatment of relapses post-SCT with DLI has been considerably less successful for acute leukaemias than in CML. 9 In a previous study, comparing the outcomes of MUD and sibling graft recipients, we found a significant difference in occurrence of relapse between children who did or did not develop chronic GVHD. 2 We decided to further investigate this issue in the entire group of children transplanted for acute leukaemias at our c...

An association of a viral infection in utero and development of acute lymphoblastic leukemia (ALL) has been suggested. Cytomegalovirus (CMV) has been reported as a leading agent of intrauterine infections resulting in some cases of congenital infections. The authors investigated the presence of prenatal CMV infection in children who later developed ALL. Guthrie cards were obtained from 48 children with ALL and 46 healthy children and were analyzed for the presence of CMV DNA by a real-time TaqMan PCR. CMV DNA was not detected in Guthrie cards from the children with ALL, from the control healthy children. The results show that prenatal CMV infection does not seem to be associated with later development of childhood ALL.