 Acute and late side effects of TBI in combination with other chemotherapeutic are manifold to the growing organism and include severe organ dysfunctionfailure due to toxicity. Although transplant associated mortality was reduced after HSCT in the last decade due to better HLA matching, infection prevention and control, the burden of late complications is still a matter of concern.Growth retardation, hormonal dysfunction, sterility and the risk of secondary cancer are the late consequences of TBI in children.However, so far no prospective study has demonstrated similar outcomes in paediatric ALL using chemo-conditioning regimen before HSCT.The reason for that are manifold: only a minority of children with ALL qualify for allogeneic HSCT as most patients are cured with modern chemotherapy approaches alone. Those with dismal prognosis are treated in HSCT centres that care for patients with different diseases. Therefore it is nearly impossible to answer complex outcome questions in single centres or even in single countries. International cooperation are essential to allow prospective randomized investigation within comparable patient cohorts. This study aims to explore the efficacy and efficiency of two different chemo-conditioning regimens FluThio with Treo or ivBu in comparison to the standard conditioning regimen TBIVP16. All patients with an indication for HSCT, age 4 years and a matched donor MD or matched sibling donor MSD undergo randomisation between these two conditionings. The decision if the irradiation free conditioning is FluThioTreo or FluThioivBu is stratified by country. Patients with age 4 years receive automatically the irradiation free conditioning. Patients with a mismatched donor are stratified according to the donors stem cell source cordblood, haploidentical tx or bone marrowperipheral blood stem cells. 