Acute Lymphoblastic Leukemia (ALL) is now having over 80% event-free survival after frontline chemotherapy treatment. There is still 15-20% of patients having a relapse after initial control. Relapsed ALL is associated with lower second remission rate and also high chance of further relapse. Currently there are only a few large scale studies targeting this challenging disease. BFM Relapsed ALL studies have been organized since 1990s and have identified several important prognostic factors, including timing and site of relapse and also immunophenotyping. COG has performed several studies on relapsed ALL (AALL02P2, AALL0433, ADVL04P2) but the results are rather fragmented. Recently UK group conducted a nationwide randomized study, ALL R3 study, testing the type of anthracycline and prognostic value of minimal residual disease after induction therapy.

T-ALL relapse is having poor prognosis except for the late isolated extramedullary relapse. Long-term survival of T-ALL bone marrow relapse treated with chemotherapy is less than 10%, thus allogeneic stem cell transplant is always indicated. Whereas B-ALL has been better studied and the risk stratification of relapsed ALL is better defined.

According to previous studies, patients can be stratified into Standard, Intermediate and High-Risk groups based on site of relapse, time of relapse from first diagnosis and immunophenotyping. Early bone marrow relapse at less than 18-36 months from diagnosis is having the worst prognosis and is classified as HR. Those with late relapse at >36 months from diagnosis is in general having a better prognosis. Bone marrow relapse is having a poorer outcome as compared to isolated extramedullary relapse (IEM). Somehow combined marrow and extramedullary relapse appear to have a better prognosis than isolated bone marrow relapse. Early B-ALL marrow relapse was only having 15-30% long-term survival, and early B-ALL IEM around 30-50% survival.

Late B-ALL marrow relapse has a higher second remission rate of around 95% and also better long term survival of 50-60%. Late B-ALL IEM is having a better prognosis of up to 70-80% survival. Based on the above criteria, several study groups including BFM, UK and COG also adopted similar strategies of stratifying patients and delivered risk-adapted treatment, with some minor variation among these groups.