Prognostic impact of CEBPA mutational subgroups in adult AML

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIPInDel), frameshift InDel or nonsense mutations inducing translational stop (bZIPSTOP) or single base-pair missense alterations (bZIPms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIPInDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIPInDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIPInDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIPInDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIPms)

Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial

International audienceIn t(8;21)(q22;q22) acute myeloid leukemia, the prognostic value of early minimal residual disease assessed with real-time quantitative polymerase chain reaction is the most important prognostic factor, but how long-term minimal residual disease monitoring may contribute to drive individual patient decisions remains poorly investigated. In the multicenter CBF-2006 study, a prospective monitoring of peripheral blood and bone marrow samples was performed every 3 months and every year, respectively, for 2 years following intensive chemotherapy in 94 patients in first complete remission. A complete molecular remission was defined as a (RUNX1-RUNX1T1/ABL1)×100 ≤ 0.001%. After the completion of consolidation therapy, a bone marrow complete molecular remission was observed in 30% of the patients, but was not predictive of subsequent relapse. Indeed, 8 patients (9%) presented a positive bone marrow minimal residual disease for up to 2 years of follow-up while still remaining in complete remission. Conversely, a peripheral blood complete molecular remission was statistically associated with a lower risk of relapse whatever the time-point considered after the completion of consolidation therapy. During the 2-year follow-up, the persistence of peripheral blood complete molecular remission was associated with a lower risk of relapse (4-year cumulative incidence, 8.2%), while molecular relapse confirmed on a subsequent peripheral blood sample predicted hematological relapse (4-year cumulative incidence, 86.9%) within a median time interval of 3.9 months. In t(8;21)(q22;q22) acute myeloid leukemia, minimal residual disease monitoring on peripheral blood every 3 months allows for the prediction of hematological relapse, and to identify patients who could potentially benefit from intervention therapy

Outcomes Following Hematopoietic Stem Cell Transplantation in Patients Treated with Chemotherapy with or without Gemtuzumab Ozogamicin for Acute Myeloid Leukemia

International audienc

How to prevent relapse after allogeneic hematopoietic stem cell transplantation in patients with acute leukemia and myelodysplastic syndrome

Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in acute myeloid leukemia (AML) patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory hematological malignancies or with persistent molecular or radiological (PET-CT scan) residual disease. For high risk AML and myelodysplasia (MDS), a post transplant maintenance strategy is possible, using hypomethylating agents or tyrosine kinase inhibitors (TKI) anti-FLT3 when the target is present. For Philadelphia positive acute lymphoblastic leukemia (ALL), there is a consensus for the use of TKI anti BCR-ABL as post transplant maintenance