Certain genetic alterations, including mutations and copy number alterations, can predict survival outcomes for patients with myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (AML) who have undergone allogenic hematopoietic cell transplantation (AHCT), according to a study published in Blood.
“[These alterations] are central to the pathogenesis of myelodysplastic syndromes and related diseases,” Tetsuichi Yoshizato, MD, PhD, from the Kyoto University Department of Pathology and Tumor Biology, and co-authors wrote, “[We explored] their roles in allogeneic hematopoietic cell transplantation in a large cohort of patients.”
Dr. Yoshizato and co-authors enrolled patients diagnosed with MDS or MDS/myeloproliferative neoplasms (MPN) who had received AHCT between 1998 and 2014. Patients were eligible for inclusion if they were ≥16 years old at the time of transplant and had available DNA samples.
Of the 797 patients with MDS, 77.4 percent (n=617) had genetic alterations, including 1,776 mutations and 927 abnormal copy segments. In multivariate analyses, the authors determined that TP53 mutations, RAS-pathway mutations, and a complex karyotype were indicators of poor post-AHCT survival.
The negative effects of TP53 mutations and a complex karyotype on prognosis were evident regardless of disease subtype, the authors reported, while “the effects of RAS-pathway mutations depended on disease subtype and were confined to myelodysplastic/myeloproliferative neoplasms.”
“For patients with mutated TP53 or complex karyotype alone, long-term survival could be obtained with AHCT,” the authors concluded. The study was limited by the variations in patients’ clinical characteristics, treatments, and the inability to adjust for some confounding factors.
Source: Yoshizato T, Nannya Y, Atsta Y, et al. Impact of genetic alterations in stem-cell transplantation for myelodysplasia and secondary acute myeloid leukemia. Blood. 2017.