CD20 expression associates with extramedullary involvement at diagnosis and indicates a poor prognosis in adults with de novo Ph-negative B-cell precursor acute lymphoblastic leukemia

【摘要】：Objective:To investigate the characteristics of patients with CD20 expression and the influence of CD20 expression on the outcome of adults with the Ph-negative B cell precursor acute lymphoblastic leukemia(BCP-ALL).Method:From January 2000 to December 2013,217 consecutive adult patients were diagnosed as de novo Ph-negative BCP-ALL and treated in Peking University People's Hospital,Peking University Institute of Hematology.CD20-positive was defined as 20%leukemia cells expression detected by flow cytometry.All patients were administered CODP±L regimen as induction,alternative high dose methotrexate(MTX) and CODP regimen or hyper-CVAD regimen as consolidation for 3 to 4 cycles.Patients who remained in the first complete remission(CR) were designated to the chemotherapy group and the allogeneic hematopoietic stem cell transplantation(allo-HSCT) group based on the donor availability and their intentions.Patients of allo-HSCT group accepted a modified BUCY or TBI-CY based regimen as conditioning regimen.Patients who were not candidates of allo-HSCT continued the consolidation and maintenance therapy for 1-1.5 years.Intrathecal chemotherapy was the routine prophylaxis and treatment for central nervous system leukemia(CNSL).Rituximab was not included in regimens.Result:Among the 217 patients,106(48.8%)were male and 111(51.2%) were female,with a median age of 32 years(range:18 to 64 years)at diagnosis.Sixty-eight(31.3%)patients were determined as CD20 positive.Patients' characteristics at diagnosis,including gender,age,WBC count,hemoglobin,platelet count,cytogenetic risk assessed according to MRC UKALLXII/ECOG E2993 adult ALL classification were similar between the CD20-positive and the CD20-negative groups,except higher incidences of lymphadeopathy/hepatosplenomegaly(41.2%vs.25.5%,P=0.025) and extramedullary involvements(13.2%vs.2.0%,P=0.002) were in the CD20-positive group.Early CR rates followed the first inductive regimen(77.9%vs.81.9%,P=0.496) and the final CR rates(96.0%vs.89.7%,P=0.118) were comparable in the two groups.Among 175 patients who achieved the early CR,76(43.4%) underwent allo-HSCT and 99(56.6%) treated with chemotherapy alone.The baseline patients' characteristics were compatible between the allo-HSCT and the chemotherapy groups.With a median follow-up of 32.0 months(range:2.0-169.0 months) in survivors,the allo-HSCT group had significantly higher 3-year disease free survival(DFS,75.3%vs.3.3%,PO.001) and overall survival(OS,76.2%vs.3.9%,PO.001) rates than the chemotherapy group.In the chemotherapy group,significantly lower3-year DFS(8.2%vs.37.6%,P=0.001) and OS(11.3%vs.46.7%,PO.001) rates were found in the CD20-positive subgroup than those in the CD20-negative subgroup.Multivariate analyses identified CD20 expression was an unfavorable prognostic factor of both DFS(HR:2.054,P=0.048) and OS(HR:3.013,P=0.016).In addition,WBC ≥30×10~9/L at diagnosis was another adverse predictor of DFS(HR:2.361,P=0.013).Nonetheless,among patients underwent allo-HSCT,none of risk factors such as CD20 expression and WBC≥30×10~9/L could be found to impact on 3-year OS and DFS rates.Conclusion:CD20 expression was associated with lymphadeopathy/hepatosplenomegaly and extramedullary involvement,and had an adverse impact on the outcome of adults with Ph-negative BCP-ALL.Allo-HSCT could overcome the unfavorable prognostic factor of CD20 expression.