Clinical Analysis Of Extramedullary Relapses After Allogeneic Hematopoietic Stem Cell Transplantation For Leukaemia

Objective:To investigate the incidence,risk factors,treatment and clinical outcome of extramedullary relapse following allogeneic hematopoietic stem cell transplantation(allo-HSCT), and explore the possible pathogenesis.Methods:We retrospectively analyzed 9 cases of isolated extramedullary relapse(EMR) from 164 leukemic patients underging allo-HSCT from April 1997 to December 2009.The 10 clinical parameters were selected for Cox univariate analysis:gender,age,underlying disease,donor type,disease status at transplant,HLA disparity,acute GVHD,chronic GVHD,EM involvement prior to transplantation and conditioning regimen.Factors that were significant at the 0.10 level on univariate analysis were evaluated by multivariate analysis using a Cox regression.The study also involved the assessment of therapeutic options for EMR,and the discussion of the possible pathogenesis.Results:1.The incidence of overall relapse was 17.7%(29/164),with 17 cases of medullary relapse(10.4%),9 cases of isolated extramedullary relapse(5.5%) and 3 cases of extramedullary relapse with concomitant bone marrow involvement(1.8%).2.The following factors were associated with an increased risk of EM relapse by univariate analysis:gender,donor type, disease status at transplant,chronic GVHD,EM involvement prior to transplantation.These risk factors were entered into a multivariate model.Only advanced stage of the disease(RR=8.753, P=0.012),absence of chronic GVHD(RR=0.034,P=0.005) and EM involvement prior to transplantation(RR=49.864,P=0.000) were identified as being significantly associated with the occurrence of EM relapse.Conclusion:Our study showed that advanced stage of the disease,absence of chronic GVHD and EM involvement prior to transplantation were independently associated with an increased risk of EM relapse.Many factors involved in the pathogenic mechanism of EM relapse are not mutually exclusive and may co-exist and interact in patients.As graft-versus-leukemia(GVL) effect in extramedullary sites is not as potent as in bone marrow,the extramedullary sites may be "sanctuary sites" from the GVL effect.Therefore,immune escape might play a major role in the pathogenesis of EM relapse.