| Objective:In recent two decades,with development in diagnosis and treatment of leukemia,the rate of complete remission of childhood acute leukemia and the long-term disease-free survival time have been improved greatly.However, about 30%of children will relapse ultimately.The minimal residual disease(MRD) has been confirmed to result in relapse and affect the long-term survival of children in the past decades. In this paper,the different methods and their clinical application for MRD detection were systemically reviewed.Metheds:To search the documents utilizing the CNKI and China Biomedicine databases,PubMed and Highwire press database.Results:There are many metnods to detect MRD,the key point is to discover the minimal residual leukemia cells that mixed in normal hematopoietic cells.In recent two decades,the research findings of cytobiology have demonstrated that if the leukemia cells were less than 106(the weight is lower than lmg), the clearance of MRD utilizing the individual immunoprotection may become possible.So the sensitivity suited for MRD detection is at least 10-4.Whereas the sensitivities of morphological examination,cytogenetics method and fluorescence in situ hybridigation(FISH) are 5×10-2,10-1-10-2 and 10-2-10-3 respectively,therefore,the clinical application is limited.With the development of molecular biology and molecular immunology,flow cytometry(FCM) and quantitative polymerase chain reaction(PCR) assessment have improved, which make the sensitivity of MRD detection get a step further. FCM distinguishes the malignant cells by detecting the leukemia-associated antigen phenotype.The antibody combinations when following up are decided according to the abnormal phenotype features at the time of diagnosis.Usually, at least one sort of combinations should be selected,of which the sensitivity is 10-4-10-5.MRD detection with PCR includes rearrangement of antigen receptor genes,chromosomal translocation and amplification of fusion transcripts,of which the sensitivity is 10-4-10-6,this allows for measurement of 85% of ALL and 30%of AML cases.Numerous clinical studies demonstrate that the existence of MRD reflects the therapeutic effect,and it is closely related to the clinical outcome.Moreover,continual monitoring may provide more information for clinical outcome.MRD detection can classify the risk of leukemia,which makes the individual chemotherapy become possible.In addition,the quantitative detection of MRD before transplant is a significant predictor for relapse after bone marrow transplantation.Conclusions: 1.There are so many techniques to detect MRD,but no one suits all cases.2.The comprehensive analysis of leukemia-associated antigen phenotype,abnormal chromosome and fusion transcripts with FCM,FISH and PCR can make the MRD detection get a step further.3.It should be emphasized to detect MRD at different stages of chemotherapy instead of only one time.Continual MRD detection has independent prognostic significance.4.The risk classification based on MRD detection is more prognostic for T-ALL than B-ALL.
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