Specific cytogenetic abnormalities are associated with patient outcomes after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) and may have prognostic value, according to a study published in Leukemia.
A multinational research team conducted a retrospective analysis of clinical outcomes of patients with AML undergoing allogeneic HSCT while taking into account recurring cytogenetic abnormalities and FLT3-ITD status. The primary endpoint was leukemia-free survival (LFS).
Using the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) registry, the researchers studied a cohort of 8558 adult patients with AML who underwent first allogeneic HSCT during first remission and were registered between 2006 and 2016. Patients had a median age of 52 years (range, 18-77).
Normal baseline karyotypes were found in 52.6% of patients (4530/8558). A monosomal karyotype was identified in 6.2% of patients (533/8558), and 5.9% of patients had complex karyotypes (507/8558). Trisomy 8 (8.8%), monosomy 7 (5.2%), and chromosome 5q abnormalities (4.6%) were the most common abnormalities.
Patients with monosomy 7, del(5q), 17p abnormalities, t(10;11)(p11-14;q13-23), t(6;11)(q27;q23), and inv(3)(q21q26)/t(3;3)(q21;q26) and those with a monosomal or complex karyotype experienced significantly lower LFS compared with patients who had a normal karyotype, with hazard ratios (HRs) ranging from 1.37 to 1.76. However, some abnormalities were associated with improved LFS rates, such as trisomy 14 (HR, 0.59; 95% CI, 0.36-0.97; P =.04), del(9q) (HR, 0.59; 95% CI, 0.41-0.85; P =.004), and loss of chromosome X (HR, 0.54; 95% CI, 0.36-0.8; P =.002).
A subset of 2473 patients had FLT3-ITD data available for incorporation into a novel prognostic model. FLT3-ITD was mutated in 51% of these patients. The highest 2-year LFS rates were found in patients with either favorable risk karyotypes (489 patients; 2-year LFS rate of 72%) or intermediate risk karyotypes with nonmutated FLT3-ITD (1749 patients; 2-year LFS rate of 66%). The lowest 2-year LFS rate was found in patients with a composite of monosomal and complex karyotype (285 patients; 2-year LFS rate of 19%).
1. Canaani J, Labopin M, Itälä-Remes M, et al. Prognostic significance of recurring chromosomal abnormalities in transplanted patients with acute myeloid leukemia [published online March 7, 2019]. Leukemia. doi: 10.1038/s41375-019-0439-3