Stem cell transplantation in adult ALL patients

Less than 40% of adult acute lymphocytic leukaemia (ALL) patients will still be alive at 5 years post-diagnosis. Ways to improve patients' outcome, using high-dose therapy followed by autologous/allogeneic stem cell transplantation (SCT) in first complete remission (CR1) rather than consolidation/maintenance chemotherapy, have been investigated. However, prospective studies are small and results are inconclusive. The largest prospective trial ever being performed in adult ALL patients, the ongoing UKALL 12/ECOG 2993 trial, is assigning all patients who have a sibling donor to receive allogeneic SCT (alloSCT) in CR1, whereas all other patients are randomized to continue chemotherapy versus autologous SCT. An interim analysis of this trial seems to support an alloSCT in first CR in adult ALL patients (reflected by a significantly reduced relapse rate with an improved disease-free survival). However, less than 30% of the patients have a matched sibling donor, the majority of the patients are over 40 years old, which makes them less suitable for conventional allograft, and even in those who have a matched sibling donor and are young and fit enough to receive it the treatment-related mortality (TRM) is about 20%. Strategies for expanding donor availability, meanwhile, to reduce the TRM, remain challenges. Data regarding the efficacy of reduced-intensity regimens in ALL patients are still scanty. Another way of improving patient outcome is to select patients for allograft more carefully. There are enough data to suggest now that children who achieved a clinical remission but failed to obtain a molecular/immunological remission are more prone to relapse. Similar data have recently been published for adult ALL. However, data are still limited, and the significance of minimal residual disease (MRD) has never been studied prospectively in adult ALL patients. A reasonable approach is to assign all patients with a matched related donor who has failed to achieve a molecular/immunological remission to receive a conventional alloSCT, whereas all others might be randomized to receive alloSCT versus chemotherapy/autologousSCT. However, patients with Ph(+) ALL who have a donor should receive an alloSCT in CR1, regardless of their MRD results. It appears that alloSCT provides the best chance for cure. However, by improving our ability to select those who have the highest risk for relapse, unnecessary toxicity/mortality might be prevented and the general outcome might improve.