Clinical Characteristics And Prognosis Of Normal Karyotype In Adult Patients With BCR-ABL-Positive Acute Lymphoblastic Leukemia

ObjectiveTo investigate the clinical characteristics and the prognosis of normal karyotypes(NK)in adult patients with BCR-ABL-positive acute lymphoblastic leukemia(BCR-ABL~+ALL),so as to make a supplement in the cytogenetic prognostic stratification system for BCR-ABL~+ALL and provide the clinical treatment strategies for this special group.Setting and ParticipantsA total of 198 adult patients with BCR-ABL~+ALL patients who were newly diagnosed in the Department of Hematology,the First Affiliated Hospital of Zhejiang University from January 2010 to December 2018 and had the results of karyotype analysis were collected.According to the inclusion and exclusion criteria,a total of 76patients were analyzed in this study and divided into groups of NK/BCR-ABL~+(n=22)and isolated Philadelphia chromosome-positive(Ph~+)(n=54).The clinical characteristics and prognosis of the two groups were analyzed and compared retrospectively.Overall survival(OS)and disease-free survival(DFS)were analyzed using Kaplan–Meier curves,which were compared using the log-rank test.The Cox-regression analysis was used to further clarify the prognostic value of NK in adult BCR-ABL~+ALL patients.ResultsIn this study,the incidence of NK in patients with BCR-ABL~+ALL was 11.1%(22/198).There were no statistically significant differences in clinical characteristics and complete remission(CR)rate between the two groups.Compared with the isolated Ph~+group,the NK/BCR-ABL~+group had a higher relapse rate(55.0%vs.29.4%,P=0.044).OS and DFS were statistically significant shorter in the NK/BCR-ABL~+group than that in the isolated Ph~+group[median OS:24.5 vs.48.6(months),P=0.022;median DFS:11.0(months)vs.undefined,P=0.008].The five-year OS and DFS for patients with NK/BCR-ABL~+were 49.5%and 14.5%,respectively;and patients with isolated Ph~+were 49.5%and 55.7%,respectively.Thirty-four(44.7%)patients underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT)in this study,with 9 and 25 in the NK/BCR-ABL~+group and the isolated Ph~+group,respectively.The median OS and DFS of patients in the allo-HSCT group were not undefined,and the 5-year OS and DFS rates were 64.6%and 67.7%,respectively.The median OS and DFS of the non-allo-HSCT group were 18.5 and 13.0 months,and the5-year OS and DFS rates were 12.3%and 15%,respectively.The allo-HSCT group had significantly better OS and DFS than the non-allo-HSCT group(P?0.0001 and P=0.0002,respectively).Among the patients who received allo-HSCT,the median OS and DFS in the NK/BCR-ABL~+group were 35.5 and 27.5 months,respectively,while those in the isolated Ph~+group were undefined.There was a trend of significant statistical difference in OS between the two subgroups(P=0.066),but no significant difference in DFS.Multivariate analysis revealed that NK was independently associated with poor OS[HR 2.256(95CI,1.005-5.066),P=0.049]and DFS[HR 2.711(95CI,1.319-5.573),P=0.007]in BCR-ABL1~+ALL patients.ConclusionsAdult NK/BCR-ABL1~+ALL patients have a high recurrence rate and poor prognosis.NK is an independent risk factor for the prognosis of adult BCR-ABL1~+ALL patients.Allo-HSCT can improve the survival of these patients.It is suggested that allo-HSCT should be performed as soon as possible after remission.