SummaryAlthough the combination of tyrosine kinase inhibitors with chemotherapy is widely used for young adults with Philadelphia chromosome positiveacute lymphoblastic leukaemia (Ph+ ALL), the outcome and safety of this combination using intensive paediatric-based protocols has not been well described. The clinical course of 32 adults age 18-60 years with Ph+ ALL treated with a paediatric-based protocol plus imatinib was evaluated. The complete response rate was 94%. Grade 3-4 infections, neuropathy, myopathy and liver function abnormalities were common, resulting in major treatment delays and dose reductions, and declines in performance status (physical deconditioning), particularly in patients aged 41-60 years. Median and 3-year overall survival (OS) was 40·7 months and 53%, respectively, and median and 3-year even-free survival (EFS) was 30·1 months and 50%, respectively. OS and EFS were inferior in deconditioned patients. Of 16 patients who underwent haematopoietic stem cell transplantation (HSCT) in first complete remission, six died of non-relapse complications. There was no significant difference in OS and EFS between transplanted and nontransplanted patients, based on an intention-to-treat and time-to-donor identification analysis. The combination of imatinib with a paediatric-based regimen in adults produced high response rates, but was associated with considerable toxicity and high non-relapse mortality post-HSCT.Keywords: leukaemia, chemotherapy, haematopoietic stem cell transplantation, acute lymphoblastic leukaemia, tyrosine kinase inhibitors.Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) has long been recognized as a high-risk subset of ALL. Published data show a disappointing longterm survival of 20% or less with chemotherapy alone (Dombret et al, 2002;Faderl et al, 2010). The combination of BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs), most commonly imatinib, with multi-agent chemotherapy regimens has improved outcomes, with complete response rates of 80-90%, and 5-year survivals in the 35-50% range (Thomas et al, 2004;Yanada et al, 2006; de Labarthe et al, 2007;Bassan et al, 2010;Fielding, 2010). Nevertheless, Ph+ disease remains a poor prognosis subgroup with unacceptably high relapse rates.Allogeneic haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) remains the standard of care in most centres, and is the only treatment demonstrated to cure a significant proportion of patients. Consequently, the goal of most approaches is to optimize complete response rates and prolong remission duration, thereby permitting a larger proportion of patients to proceed to HSCT in CR1. The outcome of HSCT is largely influenced by transplant-related mortality (TRM) and post-transplant relapse. Early TRM is influenced by various factors, including pretransplant patient-related issues, toxicity of the conditioning regimen, and graft-versus-host disease (GVHD) (Sorror et al, 2005;Artz et al, 2006).For Ph-negative ALL, a number of studies in adolescents ...