Analysis Of Risk Factors And Therapy For Relapse Of Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

Objective: To analyze the risk factors of patients with relapsed leukemia after allogeneic hematopoietic stem cell transplantation,then to explore the treatment strategies for recurrence.Methods: We conducted a single center retrospective study containing 202 cases of leukemia received allo-HSCT from March 2004 to October 2014,including 83 ALL,65 AML containing myelodysplastic syndrome(MDS)into the AML(3 cases),46 CML containing chronic phase(CP)42 cases,accelerate phase(AP)in 2 cases and blastic period(BP)in 2 cases,5 CMML,3 ATLL.192 patients achieved complete remission(CR)and 10 stayed non-remission(NR)before transplantation.14 patients had extramedullary disease prior to transplant.The median time of disease diagnosis to transplant was 7(1-60)months.Conditioning regimen were TBI/CY/Ara-C(63cases)or BU/CY/Ara-C(116 cases)or BU/CY(23 cases).There were 105 cases of male donor and 97 cases of female donors,among them 175 were related donors,27 were unrelated.Between donor and recipient different gender were 104 cases,the same gender with 98 cases,matching blood type of 120 cases,out of 82 cases with mismatching blood type.CSA and short-term MTX were used to prevent GVHD in patients after HLA-identical sibling transplant.In the HLA-matched unrelated donor and haploidentical stem cell transplantation we added ATG and MMF to prevent GVHD.A median of 9.12(4.5-22.2)x 108/kg karyocyte and 3.92(1.06-11.56)x 106 / kg CD34+ cells were transfused.Using cox proportional hazard regression model for univariate and multivariate analysis method to screen the risk factors for recurrence after transplantation.Results: All patients with successful graft implantation,the median time of granulocyte implantation was 15(9-26)days after transplantation.In the leukemia patients who underwent allo-HSCT,68 cases relapsed,of them 33 patients were bone marrow morphological recurrence,20 patients with minimal residual positive,15 cases of extramedullary relapse.The recurrence rate was 33.6%.The median time to recurrence was 4(1.5-26)months after transplantation.Among the types of the relapsed cases,ALL came first(50%),AML second(30.8%)and CML at least(16.1%).Univariate analysis indicated that there were five risk factors related with the disease relapse(P<0.05),including the type of disease,extramedullary disease prior to transplant,the course of induced remission,the status of disease at HSCT and chronic GVHD.The gender and age of recipients,the time of disease diagnosis to transplant,blood type,the type and gender of donors,stem cell source,conditioning regimen,karyocyte number,time of granulocyte implantation,the prevention of GVHD,acute GVHD,cytomegalovirus infection had little effect on the relapse of leukemia after transplantation.Multivariate analysis determined that extramedullary disease prior to transplant(RR=2.622,95%CI1.139~6.037),the course of induced remission(RR=1.156,95%CI 0.682~1.957),chronic GVHD(RR=1.728,95%CI 0.999~2.991)were independent risk factors for relapse of the patients who had undergone transplantation.Treatment strategies in patients with recurrence included withdraw immunosuppressant,donor lymphocyte infusion,systemic chemotherapy and localradiotherapy,targeted therapy,second transplantation.Individualized choice was needed according to the site of recurrence.The relapse-related mortality was 25.2%.Conclusion: The type of disease,extramedullary disease prior to transplant,the course of induced remission,the status of disease at HSCT and chronic GVHD were the factors related with disease relapse after HSCT.With poor prognosis in patients with leukemia relapse after allo-HSCT,early interference treatment has good effect.The evaluation and prevention of risk factors before transplantation is even more important.