| Background:Philadelphia(Ph) chromosome is a special chromosome ectopic phenomenon, which is resulted from the t(9;22) chromosome translocation, with a special genetic abnormality known as the BCR-ABL fusion gene. This translocation occurs in most of chronic myelogenous leukemia(CML), a subset of cases of acute lymphoblastic leukemia(ALL) and a few of acute myeloid leukemia(AML)patients. The incidence of Ph+ALL is 20%~30% in adult ALL, although its complete remission rate is 80 %-90 % with standard induction, but most patients relapsed in short term and long-term prognosis of Ph+ALL is very poor, and it is considered as one of the high-risk or advanced leukemias. Due to the graft-versus-tumor effect, allogeneic stem cell transplant(allo-HSCT) in CR remains the only curative option for Ph+ ALL patients, however, this treatment is largely limited because of the high treatment related mortality and relapse rate. Recently, the BCR-ABL tyrosine kinase inhibitor(TKI), imatinib, has substantially improved the prognosis of patients with Ph+ ALL, and allows more patients have the eligible for allo-HSCT. However, the correct way to combine allo-HSCT and imatinib is still controversial. In recent years, several studies reported the efficacy and safety of the use of imatinib after transplantation, but the results are conflictive. This study aim to compare the effect of the post-transplant imatinib maintenance therapy with no-IM therapy, and the the effect of post-transplant IM administered prophylactically with IM administered after the detection of MRD by Systematic review, to provide reliable evidences for the treatment of post-transplant Ph+ ALL patients.Objective:To compared the effect of the post-transplant imatinib maintenance therapy with no-IM therapy, and the the effect of post-transplant IM administered prophylactically with IM administered after the detection of MRD by the way of Systematic review.Methods:on the basis of the reasonable development of search strategies, firstly, we searchedPub Med, the Cochrane Library, EMbase, CNKI, Metaregister of controlled trials,VIP,CBM, Wan Fang Data, and hand searched the related journals to collect literatureswhich compared the effect of the post-transplant imatinib maintenance therapy withno-IM therapy, and also the the effect of post-transplant IM administeredprophylactically with IM administered after the detection of MRD. Only controlledclinical trials were included. All searches were from the date of establishment to April10th 2014. After extracted data and quality assessment, we used the Cochrane softwareRev Man 5.2 to do meta-analysis, and the result indicators were overall survival(OS) rate,Disease-free survival(DFS) rate, the engraftment time of white blood cell and platelet,relapse rate and treatment-related mortality(TRM).Results:After strict screening, a total of 7 controlled clinical trials were included in our study, with 366 post-transplant Ph+ALL patients. The included trials aimed to compared the effect of the post-transplant imatinib maintenance therapy with no-IM therapy, and the the effect of prophylactically IM administered after allo-HSCT with IM administered after the detection of MRD. The results of the systematic review showed that there were statistically significant difference between post-transplant imatinib group and no-IM group on overall survival(OS)rate(HR=0.22, 95%CI 0.17 to 0.27), Non-relapse mortality(NRM) rate(HR=0.41, 95%CI 0.20 to 0.82), Disease-free survival(DFS) rate(HR=0.84, 95%CI 0.80 to 0.89).However, it is showed that Post-transplant imatinib therapy had no significant influence on the engraftment of platele(MD=0.78, 95%CI-1.59 to 3.16) and white blood cell(MD=-0.92, 95%CI-4.35 to 2.50).The influence of Post-transplant imatinib therapy on relapse rate is still controversial. When compared the prophylactically IM administered after allo-HSCT with IM administered after the detection of MRD, the results showed that prophylactic IM prolonged the duration of PCR negativity and could prevented molecular recurrence after SCT, but had no significant influence on OS,DFS, EFS and RD, in addition, detection of BCR-ABL transcripts in early stage after SCT may associated with a significantly inferior outcome.Conclusions:The results of our systematic review showed that post-transplant imatinib maintenance therapy did not shorten the time of the engraftment of white blood cell and platelet after allo-HSCT, but it could improve OS and DFS rate in the post-transplant Ph+ALL patients, and also reduce the NRM rate. However, the influence of post-transplant imatinib therapy on relapse rate is still controversial. Only 1 randomized controlled trial reported the data about different start point of post-transplant imatinib therapy, its results showed that prophylactic IM after allo-SCT could prolonged the duration of PCR negativity, and could prevented post-transplant molecular recurrence, however, it had no significant influence on OS rate, DFS rate, EFS rate and RD. Due to the limitations of the included trials, this conclusion of our systematic review need to be verified by further studies. |
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