Prognostic Impact of t(9;11) and Del(7q) As Intermediate-Risk Abnormalities in AML Following Allo-Transplant: Insights from the ELN 2022 Classification - an EBMT ALWP Study

Background: The recently updated ELN 2022 risk classification has redefined several genetic abnormalities and their associated risk categories in acute myeloid leukemia (AML), treated with intensive chemotherapy. The presence of t(9;11)(p21.3;q23.3) takes precedence over rare, concurrent adverse-risk abnormalities and is categorized as intermediate-risk. Similarly, the deletion of 7q as a sole abnormality is under the intermediate-risk category. It is imperative to validate the prognostic implications of these specific subcategories in the context of allogeneic hematopoietic cell transplantation (allo-HCT). Methods: This is a retrospective, registry-based analysis from the European Society for Blood and Marrow Transplantation (EBMT) with the approval of the EBMT Acute Leukemia Working Party. Adult patients aged more than 18 years with a diagnosis of AML who received an allo-HCT in first remission (CR1) between 2010 and 2022, with an available full karyotype at diagnosis were included. We selected those with t(9;11) and any other associated abnormality for the first analysis, and del(7q) for the second analysis for which patients with del(5q), monosomy 7 not classified as complex, or monosomal karyotype and without other adverse abnormalities were used as a comparative group. Results: We identified 141 patients with t(9;11). Most of these patients had clinically defined de novo AML (72%), with a median age of 46 years (range: 19-71), and 60% were females. Patients received primarily myeloablative conditioning (57%) and peripheral blood stem cells (88%) from matched sibling (24%), unrelated (59%), and haploidentical donors (14%). Of those, 32 (23%) had additional adverse cytogenetic abnormalities, mostly (75%) complex karyotype. There were no significant differences in baseline characteristics between those with or without additional adverse cytogenetic alterations. After a median follow-up of 3 years, the 2-year relapse incidence (RI), leukemia-free survival (LFS), and overall survival (OS) did not show significant differences between patients with t(9;11) and those with t(9;11) plus additional adverse abnormalities (22% versus (vs.) 18.2%, p=0.85; 66% vs. 76%, p=0.42; 72% vs. 75%, p=0.68). In the second group, we identified 250 patients, including 84 with del(7q), 71 with del(5q) and 95 with monosomy 7. The majority had de novo AML (59%), with a median age of 59 years (range: 19-78), and 53% were females. Most patients received reduced-intensity conditioning (65%) and peripheral blood stem cells (90%) from matched sibling (20%), unrelated (63%), and haploidentical donors (15%). There were no significant differences in baseline characteristics among the three groups. After a median follow-up of 3 years, the 2-year RI, LFS, and OS were not different across del(7q), del(5q), and monosomy 7 (24% vs. 29% vs. 25%, HR=1.07, p=0.85 and HR=1.26, p=0.51 for del(5q) and monosomy 7 compared to del(7q); 61% vs. 52% vs. 59%, HR=1.05, p=0.86 and HR=1.26, p=0.4; 69% vs. 65% vs. 62%, HR=1.13, p=0.68, and HR=1.02, p=0.95 respectively). Conclusion: Our analysis demonstrates that the presence of additional adverse abnormalities does not significantly impact the post-transplant outcomes in patients with t(9;11) undergoing allo-HCT in CR1. Similarly, no significant differences were observed in the post-transplant outcomes among patients with del(7q) reclassified as intermediate risk, and patients with del(5q) or monosomy 7, classified as adverse-risk in ELN2022. These findings suggest that the prognostic value of the t(9;11) as intermediate-risk remains consistent in the setting of allo-HCT, whereas del(7q) confers a comparable adverse risk as monosomy 7 and del(5q).