A revised definition for cure of childhood acute lymphoblastic leukemia
LEUKEMIA
Authors: Pui, C. H.; Pei, D.; Campana, D.; Cheng, C.; Sandlund, J. T.; Bowman, W. P.; Hudson, M. M.; Ribeiro, R. C.; Raimondi, S. C.; Jeha, S.; Howard, S. C.; Bhojwani, D.; Inaba, H.; Rubnitz, J. E.; Metzger, M. L.; Gruber, T. A.; Coustan-Smith, E.; Downing, J. R.; Leung, W. H.; Relling, M. V.; Evans, W. E.
Abstract
With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse).
Clinical Evaluation of Massively Parallel RNA Sequencing for Detecting Recurrent Gene Fusions in Hematologic Malignancies
JOURNAL OF MOLECULAR DIAGNOSTICS
Authors: Kim, Borahm; Lee, Hyeonah; Shin, Saeam; Lee, Seung-Tae; Choi, Jong Rak
Abstract
The application of next-generation sequencing (NGS) technology in clinical diagnostics should proceed with care. We have evaluated the clinical validity of two commercially available RNA fusion panels, the TruSight RNA fusion panel (Illumina) and FusionPlex Pan-Heme Kit (ArcherDx), to detect recurrent translocations in hematologic malignancies. Twenty-four bone marrow samples taken at the initial diagnosis of patients with acute leukemia and chronic myeloid leukemia were included. To assess the limit of detection, serial dilutions of BCR-ABL1 (e1a2)-positive RNAs were prepared using a commercial reference material. Both NGS panels detected 19 cases with recurrent translocations identified with RT-PCR, as well as a case with KMT2A-AFF1 with false-negative results on RT-PCR. Two rare translocations, DDX3X-MLLT10 and NUP98-H0XC13, were additionally identified using NGS panels. The detection limit ranged from 10(-1) to 10(-2), which was not satisfactory for samples with low tumor burden. To conclude, RNA fusion panels were suitable for the initial diagnosis; however, for follow-up samples, conventional RT-PCR should be selected.