How to treat relapsed acute lymphoblastic leukemia: transplant vs. conventional chemotherapy

Management of relapsed acute lymphoblastic leukemia (ALL) is challenging and far from satisfactory. The treatment approaches are often varied and controversial. The duration of first remission, site of relapse, immunophenotypic and molecular characteristics of relapsed disease and response to therapy influence treatment outcome. There are three main therapeutic options i.e., chemotherapy alone, induction chemotherapy followed by HLA matched allogeneic transplant and palliation. These may be chosen based on the above mentioned factors. The response to therapy may be evaluated morphologically or by minimal residual disease (MRD). Persistence of MRD, as assessed by molecular techniques or through flowcytometry, clearly influences prognosis in children with relapsed ALL. It not only helps in identifying the subset of patients likely to benefit from allogeneic bone marrow transplant (ABMT) but also in determining the timing of transplant. Patients with non-T phenotype, with late relapsing disease and good response to re-induction therapy have been shown to do equally well with chemotherapy alone. On the other hand patients with early relapse and poor initial response are selected for ABMT. With the improvement in supportive care, better selection of HLA match donors and better immunosuppressive therapies, transplant related mortality has decreased considerably. Despite all of these overall salvage rates are still poor and novel agents are being tested in various trials to establish their role in relapsed ALL therapy.