Molecular Detection of Minimal Residual Disease before Allogeneic Stem Cell Transplantation Predicts a High Incidence of Early Relapse in Adult Patients with NPM1 Positive Acute Myeloid Leukemia.
We analyzed the impact of alloHSCT in a single center cohort of 89 newly diagnosed NPM1 AML patients, consecutively treated according to the Northern Italy Leukemia Group protocol 02/06 [NCT00495287]. After two consolidation cycles, the detection of measurable residual disease (MRD) by RQ-PCR was strongly associated with an inferior three-year overall survival (OS, 45% versus 84%, p = 0.001) and disease-free survival (DFS, 44% versus 76%, p = 0.006). In MRD-negative patients, post-remissional consolidation with alloHSCT did not provide a significant additional benefit over a conventional chemotherapy in terms of overall survival [OS, 89% (95% CI 71-100%) versus 81% (95% CI 64-100%), p = 0.59] and disease-free survival [DFS, 80% (95% CI 59-100%) versus 75% (95% CI 56-99%), p = 0.87]. On the contrary, in patients with persistent MRD positivity, the three-year OS and DFS were improved in patients receiving an alloHSCT compared to those allocated to conventional chemotherapy (OS, 52% versus 31%, p = 0.45 and DFS, 50% versus 17%, p = 0.31, respectively). However, in this group of patients, the benefit of alloHSCT was still hampered by a high incidence of leukemia relapse during the first year after transplantation (43%, 95% CI 25-60%). Consolidative alloHSCT improves outcomes compared to standard chemotherapy in patients with persistent NPM1 MRD positivity, but in these high-risk patients, the significant incidence of leukemia relapse must be tackled by post-transplant preemptive treatments.
['Lussana|Federico|F|0000-0002-6510-8616', 'Caprioli|Chiara|C|', 'Stefanoni|Paola|P|', 'Pavoni|Chiara|C|', 'Spinelli|Orietta|O|0000-0003-0374-1536', 'Buklijas|Ksenija|K|', 'Michelato|Anna|A|', 'Borleri|GianMaria|G|', 'Algarotti|Alessandra|A|', 'Micò|Caterina|C|', 'Grassi|Anna|A|', 'Intermesoli|Tamara|T|', 'Rambaldi|Alessandro|A|']
allogeneic stem cell transplantation acute myeloid leukemia nucleophosmin (NPM1)