To determine the prognostic impact of monosomal karyotype (MK) in acute myeloid leukemia (AML) in the context of the current World Health Organization (WHO) classification and to evaluate the outcome of MK+ patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of 1058 patients with abnormal cytogenetics, 319 (30%) were MK positive (MK+). MK+ patients were significantly older (p=0.0001), had lower white blood counts (p=0.0006) and lower percentages of bone marrow blasts (p=0.0004); MK was associated with the presence of -5/5q-, -7, 7q-, abnl(12p), abnl(17p), -18/18q-, -20/20q-, inv(3)/t(3;3), complex karyotype (CK), and myelodysplasia (MDS)-related cytogenetic abnormalities (p〈0.0001, each); NPM1 mutations (p〈0.0001), FLT3 internal tandem duplications (p〈0.0001) and tyrosine kinase domain mutations (p=0.02) were less frequent in MK+. Response to induction therapy and overall survival in MK+ patients were dismal with a complete remission rate of 32.5% and a 4-year survival of 9%. MK retained its prognostic impact in AML with CK, AML with MDS-related cytogenetic abnormalities, and in a revised definition (MK-R) excluding cases with recurrent genetic abnormalities according to WHO classification and those with derivative chromosomes not leading to true monosomies. In younger patients allogeneic HSCT from matched related and unrelated donors resulted in a limited improvement of overall survival. These trials are registered at www.clinicaltrials.gov as NCT00151255 and NCT00151242.
Type of Publication:
Journal article published