Impact of Additional Cytogenetic Aberrations at Diagnosis on Prognosis of Adults Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation：A Retrospective Analysis

Abstract

Additional chromosomal abnormalities(ACAs) at diagnosis are associated with inferior prognosis in chronic myelogenous leukemia. However, the prognostic significance of ACAs in adult patients with Philadelphia Chromosome Positive acute lymphoblastic leukemia (Ph + ALL) receiving TKI-targeted drugs and allogeneic hematopoietic stem cell transplantation(HSCT) is unknown. One hundred eighty-eight adult patients with Ph + ALL were retrospectively analysed, evaluating the effect of ACAs on outcomes of transplantation. One hundred thirty-six patients were included in the study. ACAs are observed in 60 cases (44%). The major-route ACAs are detected in more than 5% are as follows: +der(22), +der(9), + 8, -7 and complex karyotype. The median follow-up was 26.4 months. In the subgroup analyses of major route ACAs, three-year cumulative incidence of relapse (CIR) and progression-free survival(PFS) are statistically significant in + 8[66.7% vs.23.7%, P = 0.024; 77.8% vs. 23.7%, P = 0.0087], -7[53.8% vs. 23.7%, P = 0.035%; 61.5% vs. 32.9%, P = 0.033], and complex karyotypes[42.9% vs. 23.7%, P = 0.027; 47.6% vs. 23.7%] compared with isolated t(9;22). Additionally, the 3-year CIR for Ph + ALL with + der(22) is 44% vs. 23.7% for standard Ph + ALL(P = 0.045). The 3-year overall survival (OS) in the − 7 group is 46.5%, which is statistically significant compared with the other groups(P = 0.001). In multivariate analyses, three years CIR and PFS are statistically significant in + der(22), + 8, -7 and complex karyotype compared with standard Ph + ALL(P < 0.05). More importantly, Ph + ALL with − 7 was negatively associated with the rate of 3-year OS(P = 0.012). Partial ACAs at diagnosis appear to have a significant prognostic impact on transplantation outcomes in patients with Ph + ALL.