A Clinical Analysis Of Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Undergoing Allogeneic Stem Cell Transplantation

Around20-25%of adult acute lymphoblastic leukemia (ALL) patients are philadelphia chromosome positive (Ph+) and these Ph+ALL patients are classified as high risk and are related to a poor prognosis. Although the introduction of tyrosine kinase inhibitors has revolutionized therapy for Ph+ALL and greatly improved prognosis, allogenic hematopoietic stem cell transplantation (allo-HSCT) remains an indispensable and curable treatment. A retrospective analysis was conducted on Ph+ALL patients who received allo-HSCT in our center between2005and2012, aiming to evaluate their prognosis after allo-HSCT and find out factors related to the prognosis. A total of45patients were enrolled in our study,41patients were in complete remission (CR) before allo-HSCT, and4patients were in active disease. Thirty-five (77.8%) patients received imatinib with induction and consolidation therapy before allo-HSCT. All patients received BUCY based conditioning and mobilized peripheral stem cell from matched related (24.4%), matched unrelated (46.7%), or haploidentical (28.9%) donors. Endpoint variables included Overall Survival (OS), Relapse Free Survival (RFS), Relapse Incidence (RI) and Non-Relapse Mortality (NRM). Our results showed that3-year OS was48.5%,3-year RFS was39.1%, cumulative incidence of NRM was39.9%in the whole population. Among patients in CR at the time of allo-HSCT (n=41),3-year OS was53.5%,3-year RFS was47.6%, cumulative incidence of relapse was24%, and cumulative incidence of NRM was28.4%. Further prognostic factor analysis revealed that a high quantification of BCR/ABL transcript at the time of allo-HSCT (RR1=1.191, P=0.004; RR2=1.217, P=0.002) and Ⅲ-Ⅳ aGVHD (RR1=6.81, P=0.006; RR2=1.981, P=0.019) were unfavorable predictors for OS and RFS by both univariate and multivariate analyses. Relapse after allo-HSCT was associated with a high quantification of BCR/ABL transcript at allo-HSCT (RR=1.358, P=0.001) and a short duration between diagnosis and allo-HSCT (RR=1.021,P=0.006).Ⅲ-Ⅳ aGVHD was an independent prognostic factor of NRM (RR=6.262, P=0.023). We didn’t find a prognostic significance of pretransplant imatinib use, donor source, positivity of BCR/ABL and minimal residual disease detected by flow cytometry in predicting survival outcomes. Although a limited patients was a major drawback in our study, our results emphasized qualitative measuring of BCR/ABL transcripts was a strong predictor of survival and relapse post transplantation, and we also confirmed Ⅲ-Ⅳ aGVHD was related to a high NRM and a survival impairment. In imatinib era, further studies focusing on the kinetics of BCR/ABL transcripts before and after allo-HSCT were needed to find out the predictive value of BCR/ABL quantification.