Allogeneic bone marrow transplantation versus chemotherapy in childhood very high risk acute lymphoblastic leukemia in first complete remission: a controversial issue.

BACKGROUND AND OBJECTIVES: Improvements in the management of childhood acute lymphoblastic leukemia (ALL) did not prevent 20% to 30% of patients suffering from relapse. Moreover, the probability of relapse can rise up to 50% for some children presenting with very high risk (VHR) factors. Intensive chemotherapy and especially hematopoietic stem cell transplantation improved their outcome. The aim of this review is to assess the role of different approaches in the treatment of childhood VHR ALL on the basis of current data. EVIDENCE AND INFORMATION SOURCES: Information on the ongoing international studies was obtained via Medline. Preliminary data from a prospective cooperative study are mentioned. STATE OF ART: During the last decade, different definitions of VHR factors in childhood ALL have been a crucial issue, so that therapeutic results of single or multicenter studies were difficult to compare. All investigators agreed in adopting most aggressive treatments in patients with poor prognostic factors such as molecular biological markers, chromosomal abnormalities and biological factors including poor prednisone response and resistance to initial chemotherapy. Allogeneic bone marrow transplantation (AlloBMT) in childhood VHR ALL in first complete remission is expected to yield better event-free survival than chemotherapy. The lack of valid information in the current literature about the real impact of both chemotherapy and hematopoietic stem cell transplantation is essentially the result of the difficulty in setting up multicenter prospective studies. On the other hand, the principal biases of retrospective studies are the lack of homogeneous eligibility criteria, different first-line therapies adopted before AlloBMT and above all the waiting time to transplant which could have accounted for some of the survival advantage shown by AlloBMT patients compared to those treated with chemotherapy. PERSPECTIVES: Preliminary results of an ongoing international prospective study are presented and compare favorably with previous reports. The current scenario serves as an example of how to reach a consensus in the controversial treatment of childhood VHR ALL.