PURPOSE: While the role of minimal residual disease (MRD) assessment and the significance of achieving an MRD-negative status during treatment have been evaluated in previous studies, there is limited evidence on the significance of MRD re-emergence without morphological relapse in acute lymphoblastic leukemia (ALL). We sought to determine the clinical significance of MRD re-emergence in pediatric ALL patients. METHODS: Between 2005 and 2017, this study recruited 1126 consecutive patients newly diagnosed with ALL. Flow cytometry was performed to monitor MRD occurrence during treatment. RESULTS: Of 1030 patients with MRD-negative results, 150 (14.6%) showed MRD re-emergence while still on morphological complete remission (CR). Patients with white blood cell counts of ≥50 × 109/L (p = 0.033) and MRD levels of ≥0.1% on day 33 (p = 0.012) tended to experience MRD re-emergence. The median re-emergent MRD level was 0.12% (range, 0.01-10.00%), and the median time to MRD re-emergence was 11 months (range, <1-52 months). Eighty-five (56.6%) patients subsequently developed relapse after a median of 4.1 months from detection of MRD re-emergence. The median re-emergent MRD level was significantly higher in the relapsed cohort than in the cohort with persistent CR (1.05% vs. 0.48%, p = 0.005). Of the 150 patients, 113 continued to receive chemotherapy and 37 underwent transplantation. The transplantation group demonstrated a significantly higher 2-year overall survival (88.7 ± 5.3% vs. 46.3 ± 4.8%, p < 0.001) and cumulative incidence of relapse (23.3 ± 7.4% vs. 64.0 ± 4.6%, p < 0.001) than the chemotherapy group. CONCLUSIONS: MRD re-emergence during treatment was associated with an adverse outcome in pediatric ALL patients. Transplantation could result in a significant survival advantage for these patients.
PURPOSE: While the role of minimal residual disease (MRD) assessment and the significance of achieving an MRD-negative status during treatment have been evaluated in previous studies, there is limited evidence on the significance of MRD re-emergence without morphological relapse in acute lymphoblastic leukemia (ALL). We sought to determine the clinical significance of MRD re-emergence in pediatric ALL patients. METHODS: Between 2005 and 2017, this study recruited 1126 consecutive patients newly diagnosed with ALL. Flow cytometry was performed to monitor MRD occurrence during treatment. RESULTS: Of 1030 patients with MRD-negative results, 150 (14.6%) showed MRD re-emergence while still on morphological complete remission (CR). Patients with white blood cell counts of ≥50 × 109/L (p = 0.033) and MRD levels of ≥0.1% on day 33 (p = 0.012) tended to experience MRD re-emergence. The median re-emergent MRD level was 0.12% (range, 0.01-10.00%), and the median time to MRD re-emergence was 11 months (range, <1-52 months). Eighty-five (56.6%) patients subsequently developed relapse after a median of 4.1 months from detection of MRD re-emergence. The median re-emergent MRD level was significantly higher in the relapsed cohort than in the cohort with persistent CR (1.05% vs. 0.48%, p = 0.005). Of the 150 patients, 113 continued to receive chemotherapy and 37 underwent transplantation. The transplantation group demonstrated a significantly higher 2-year overall survival (88.7 ± 5.3% vs. 46.3 ± 4.8%, p < 0.001) and cumulative incidence of relapse (23.3 ± 7.4% vs. 64.0 ± 4.6%, p < 0.001) than the chemotherapy group. CONCLUSIONS: MRD re-emergence during treatment was associated with an adverse outcome in pediatric ALL patients. Transplantation could result in a significant survival advantage for these patients.
Authors: N Toft; H Birgens; J Abrahamsson; L Griškevičius; H Hallböök; M Heyman; T W Klausen; Ó G Jónsson; K Palk; K Pruunsild; P Quist-Paulsen; G Vaitkeviciene; K Vettenranta; A Åsberg; T L Frandsen; H V Marquart; H O Madsen; U Norén-Nyström; K Schmiegelow Journal: Leukemia Date: 2017-08-18 Impact factor: 11.528
Authors: Ching-Hon Pui; Deqing Pei; Elaine Coustan-Smith; Sima Jeha; Cheng Cheng; W Paul Bowman; John T Sandlund; Raul C Ribeiro; Jeffrey E Rubnitz; Hiroto Inaba; Deepa Bhojwani; Tanja A Gruber; Wing H Leung; James R Downing; William E Evans; Mary V Relling; Dario Campana Journal: Lancet Oncol Date: 2015-03-20 Impact factor: 41.316
Authors: Farhad Ravandi; Jeffrey L Jorgensen; Susan M O'Brien; Elias Jabbour; Deborah A Thomas; Gautam Borthakur; Rebecca Garris; Xuelin Huang; Guillermo Garcia-Manero; Jan A Burger; Alessandra Ferrajoli; William Wierda; Tapan Kadia; Nitin Jain; Sa A Wang; Sergei Konoplev; Partow Kebriaei; Richard E Champlin; Deborah McCue; Zeev Estrov; Jorge E Cortes; Hagop M Kantarjian Journal: Br J Haematol Date: 2015-10-22 Impact factor: 6.998
Authors: Donald A Berry; Shouhao Zhou; Howard Higley; Lata Mukundan; Shuangshuang Fu; Gregory H Reaman; Brent L Wood; Gary J Kelloff; J Milburn Jessup; Jerald P Radich Journal: JAMA Oncol Date: 2017-07-13 Impact factor: 31.777