Isolated extramedullary relapse in children with acute lymphoblastic leukemia : a comparison between treatment results of chemotherapy and bone marrow transplantation

The purpose of this study was to determine the therapeutic efficacy of different treatment strategies, namely chemotherapy, allogeneic and autologous bone marrow transplantation (BMT), for extramedullary relapse of acute lymphoblastic leukemia (ALL) in children in second or subsequent remission. Between 1983 and 1993, 165 patients up to 19 years of age with extramedullary relapse of ALL were registered in the multicenter ALL-REZ BFM trials. One hundred and thirty four children received chemotherapy only; 17 children were grafted from HLA-identical sibling donors 152 days (46-392 days) after diagnosis of relapse, and 14 children underwent autologous BMT after a median time of 137 (range 23-300) days. Event-free survival (EFS) at 5 years was 0.47 +/- 0.05 for patients receiving chemotherapy: 0.76 +/- 0.07 for late, 0.33 +/- 0.08 for early and 0.33 +/- 0.07 for very early relapsed patients. Sixty five patients are in complete remission (CR), 61 patients relapsed, 5 died from therapy related complications, 2 patients in CR were lost to follow-up and one patient developed a second malignancy. For patients who had undergone BMT, EFS at 5 years was 0.36 +/- 0.10 without significant difference between autologous BMT (8 of 14 in CR, 6 relapsed) and allogeneic BMT (6 of 17 in CR, 4 died of acute toxicity, and 7 relapsed). After statistical adjustment for the time to BMT, there is a significant difference (P < 0.05) between the results of chemotherapy and BMT (S-year EFS 0.50 +/- 0.05 and 0.36 +/- 0.10, respectively). The site of relapse in childhood ALL has to be considered in the treatment decision. In general BMT is felt to be the treatment of choice in case of systemic relapse. Our data suggest that BMT with its well-known therapy-related toxicity and late effects seems not to be necessary for extramedullary relapse because the chances of cure are not superior to those with salvage chemotherapy.