naa a22 4500 510740693 CHVBK 20180411083027.0 cr unu---uuuuu 180411e20130901xx s 000 0 eng 10.1007/s11845-012-0892-8 doi (NATIONALLICENCE)springer-10.1007/s11845-012-0892-8 In search of Pinkel's children: unravelling the biological heterogeneity of childhood acute lymphoblastic leukaemia by genotype and treatment molecular response [Elektronische Daten] [J. Krawczyk, S. Maguire, N. Sandys, J. Kelly, C. Ryan, A. O'Marcaigh, L. Storey, S. Rooney, C. Phillips, O. Smith] Background: Acute lymphoblastic leukaemia (ALL), the commonest childhood malignancy has seen remarkable progress since the 1960s with cure rates now approaching 85%. To achieve this patients undergo intensive treatment that usually takes 2.5-3.5years involving on average 15 different chemotherapeutic drugs. In 1971, Donald Pinkel reported Total Therapy-Protocol V that used 5 drugs and cranial radiation therapy over a similar time period. Today, one half of these patients (Pinkel's children) remain alive and free of leukaemia. Aim: The aim of this study was to evaluate the impact post-induction minimal residual disease (MRD) levels had on survival and its relationship with the more established clinical and biological prognostic predictors of outcome in the hope of identifying a subgroup of patients that are at very low risk of failure. Methods: A retrospective review of 250 Irish children with ALL was carried out. MRD status after 28days of induction chemotherapy and other known predictors of outcome were correlated with 5year event-free survival (EFS). Results: MRD status was the strongest predictor of outcome with 5year EFS rates greater that 90% seen in those patients with low-risk MRD and this was associated with TEL/AML1 rearrangement, high hyperdiploidy (HH) karyotype and female gender. Conclusion: Both MRD and karyotype are powerful determinants of outcome in childhood ALL. Therefore, it is reasonable to conclude that the majority of children cured by Pinkel et al. in the late 1960s were most likely composed of low-risk MRD, TEL/AML1 and HH patients. Royal Academy of Medicine in Ireland, 2012 Pinkel's children nationallicence ALL nationallicence MRD nationallicence Tel/AML1 nationallicence High hyperdiploidy nationallicence EFS nationallicence Krawczyk J. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut Maguire S. Trinity College, University of Dublin, 2, Dublin, Ireland aut Sandys N. Trinity College, University of Dublin, 2, Dublin, Ireland aut Kelly J. National Centre for Medical Genetics, Our Lady's Children's Hospital, Dublin, Ireland aut Ryan C. Department of Haematology, Mercy University Hospital, Cork, Ireland aut O'Marcaigh A. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut Storey L. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut Rooney S. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut Phillips C. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut Smith O. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut Irish Journal of Medical Science Springer-Verlag 182/3(2013-09-01), 377-382 0021-1265 182:3<377 2013 182 11845 https://doi.org/10.1007/s11845-012-0892-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11845-012-0892-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Krawczyk J. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut NATIONALLICENCE 700 1- Maguire S. Trinity College, University of Dublin, 2, Dublin, Ireland aut NATIONALLICENCE 700 1- Sandys N. Trinity College, University of Dublin, 2, Dublin, Ireland aut NATIONALLICENCE 700 1- Kelly J. National Centre for Medical Genetics, Our Lady's Children's Hospital, Dublin, Ireland aut NATIONALLICENCE 700 1- Ryan C. Department of Haematology, Mercy University Hospital, Cork, Ireland aut NATIONALLICENCE 700 1- O'Marcaigh A. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut NATIONALLICENCE 700 1- Storey L. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut NATIONALLICENCE 700 1- Rooney S. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut NATIONALLICENCE 700 1- Phillips C. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut NATIONALLICENCE 700 1- Smith O. Department of Haematology, Our Lady's Children's Hospital, Crumlin, 12, Dublin, Ireland aut NATIONALLICENCE 773 0- Irish Journal of Medical Science Springer-Verlag 182/3(2013-09-01), 377-382 0021-1265 182:3<377 2013 182 11845 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer