Challenging the Adverse Label: Diverse Outcomes of ELN 2022 Adverse Cytogenetic Subgroups in Acute Myeloid Leukemia Patients Allografted in First Remission: From EBMT ALWP

According to the European LeukemiaNet (ELN) 2022 classification, acute myeloid leukemia (AML) patients with intermediate or adverse risk are offered allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first remission. In this EBMT study, we included 1735 adult AML patients with ELN-2022 adverse-risk cytogenetics allografted between 2010 and 2022 in first remission (67% de novo AML, median age 56 years). Eleven non-overlapping adverse-risk cytogenetics groups were defined. The five most frequent were: Group 1 [n = 394; monosomy 17 or abn(17p); 2-year leukemia-free survival (LFS) 22%, and overall survival (OS) 25%]; Group 2 [n = 313; complex karyotype (CK) involving monosomy 5, monosomy 7, or del(5q) without monosomy 17 or abn(17p); LFS 27%, OS 37%]; Group 3 [n = 201; monosomy 5, monosomy 7, or del(5q) without CK and without monosomy 17 or abn(17p); LFS: 55%, OS: 63%]; Group 4 [n = 256; CK without monosomal karyotype (MK) or adverse additional cytogenetic abnormalities (ACA); LFS 50%, OS 61%]; Group 5 [n = 213; t(v, 11q23) without adverse ACA; LFS 50%, OS 59%]. In multivariable analysis, compared to CK without adverse ACA, LFS was negatively affected by monosomy 17 or 17p abnormalities, monosomy 5, 7, or del(5q) in the presence of CK, and t(8;16). In conclusion, this study revealed a very poor outcome of allografted AML patients with monosomy 17 or 17p abnormalities or CK involving monosomy 5, monosomy 7, and del5q. Outcomes were relatively favorable for most other ELN 2022 adverse categories, including CK with or without MK other than 5, 7, and 17, indicating that allo-HSCT can overcome their poor outcome.