| Background:Acute myeloid leukemia(AML)is a kind of malignant disease of myeloid-primed hematopoietic stem and progenitor cells.The main features of AML is the abnormal proliferation of primitive and naive myeloid cells in bone marrow and peripheral blood.The common clinical manifestations include fever?infection?hemorrhage?anemia?metabolic abnormalities?organ infiltration,etc.If the treatment is not timely,patients often died of complications such as infection and bleeding within a few months.The incidence of AML increases with age.In 2016,the US survey showed that the incidence of AML in people under 65 years old was 1.3 per 100,000,and in people over 65 years old was 12.2 per 100,000.At present,the treatment methods of AML mainly include chemotherapy,hematopoietic stem cell transplantation(HSCT),cellular immunotherapy and targeted therapy with which patients with low malignancy can often achieve long-term relief of the disease.However,the elderly patients are generally in poor condition and often accompanied by molecular mutations that can lead to poor prognosis,so conventional treatments are usually difficult to achieve the desired effects.About 70%of elderly patients will die within one year after diagnosis.Chemotherapy with intermittent infusion of HLA-mismatched donor peripheral hematopoietic stem cells for the treatment of AML is called"micro-transplantation",because it does not require the use of high-dose radiotherapy before treatment and avoid the use of immunosuppressive agents,the hematopoietic recovery of AML patients treated with micro-transplantation is faster and the infection rate is lower than those treated with general methods.The efficacy is stable in patients with AML,especially in elderly patients.The 2-year disease-free survival rate of elderly patients is increased from less than 20%to 38.9%.However,it is not completely clear whether the different clinical characteristics of patients before treatment and the characteristics of donors have an effect on the efficacy?complication and recurrence rate of micro-transplantation.The influence of number of donor CD34~+and CD3~+cells on hematopoietic recovery is not complete clear.Therefore,the aim of this study was to summarize the clinical characteristics of the 40 elderly AML patients,analyze the efficacy?complication and recurrence rate of micro-transplantation in the treatment of elderly patients with AML from age,risk prognosis stratification,HLA matching,donor gender,and doses of CD34~+and CD3~+lymphocytes,to further provide clinical guidance for treatment of AML in elderly patients with micro-transplantation.Objective:To summarize the clinical characteristics of the 40 elderly AML patients in our department of Hematology,analyze the influence of different age?risk prognosis stratification?HLA matching?donor gender on the efficacy?complication and recurrence rate of micro-transplantation in the treatment of elderly patients,analyze different doses of CD34~+and CD3~+lymphocytes on the influence of hematopoietic recovery.Method:A retrospective analysis was made of 40 elderly patients(age over 60)with acute myeloid leukemia(including MDS)who treated by micro-transplant treatment from January 2014 to October 2018 in our department of Hematology.Among them,21 were newly diagnosed and 7 were relapsed and refractory.The clinical characteristics and the remission rate of micro-transplantation induction therapy for the newly treated and relapsed elderly patients with AML were analyzed in terms of the aspects of gender?age?FAB typing?chromosome?gene?disease state before micro-transplantation?WBC?Hb?PLT number of newly diagnosed?ECOG score?risk prognosis grading,etc.Thirty-two patients in remission stage(including 12 patients who had already entered remission stage before micro-transplantation and 20 patients who had reached remission stage after induction of micro-transplantation)were divided into different groups according to age,risk prognosis stratification,HLA matching and donor gender.Statistical analysis was performed by SPSS25.0 to compare the recurrence rate(including total survival(OS),disease-free survival(DFS)and hematopoietic recovery time),complications(GVHD and the incidence of severe infection)and the recurrence rate in different groups.Results:1.The clinical characteristics of 1.40 cases of AML in the elderly were as follows:there was no significant difference in the incidence of AML between men and women,the ratio was 1:1.35(17:23);high risk was predominant,with 25 patients accounting for62.5%;FAB typing was common in M2 and M5(11 and 6,respectively,27.5%and15%);WT1/GAPDH gene mutation was found in 28 cases(70%);NPM1 gene mutation was found in 12 cases(30%)and EV L1 gene mutation(15%)in 6 cases,ETO gene mutation in 4 cases(10%),Flt3 gene mutation in 3 cases(7.5%),normal chromosome karyotype in 14 cases(35.0%),complex karyotype in 10 cases(25%),t(8;21)(q22;q22)mutation in 2 cases(5%).2.The remission rate of induction of micro-transplantation in the treatment of newly treated and relapsed refractory elderly AML:The remission rate was 76.2%in 16 of 21 newly treated elderly AML patients and57.1%in 4 of 7 relapsed and refractory AML patients,which was higher than that reported in the literature.3.The effects of age,risk prognosis classification,HLA matching and donor sex on the outcome of micro-transplantation:The difference of effects of age,risk prognostic classification,HLA matching and donor gender on the recovery time of leukocytes and platelets after micro-transplantation were not significant,;but patients with advanced age,high risk stratification,incompatibility of HLA matching,gender difference between donors and recipients(especially female donors),DFS and OS were with the trend of decrease.4.Effects of different doses of CD34~+and CD3~+T lymphocytes on hematopoietic recovery after micro-transplantation:The recovery time of leukocytes in CD34~+high dose group was faster than that in low group in the induction and the three remission courses,and there was significant difference(P<0.01)in the induction course,but there was no statistical significance in the three courses of remission period(P values were equal to 0.354?0.164?0.260,respectively).The platelet recovery time of the CD34~+high-dose group tended to be faster than CD34~+low-dose one,but the difference was not statistically significant(P values were equal to 0.214?0.790?0.524?0.438,respectively).The recovery time of leucocytes and platelets in the CD3~+high-dose group was tend to be faster,and the difference was not statistically significant(P values were equal to 0.779?0.428?0.164?0.283,and 0.320?0.755?0.738?0.075,respectively).5.Complications after micro-transplant:GVHD did not occur in 40 patients and the incidence of severe infection rate after micro-transplantation was 9.4%?14.8%and 8.3%in the three courses of remission period.There was no significant difference in the incidence of infection rates after micro-transplantation between HLA matching and donor gender.6.Recurrence after micro-transplant:The total recurrence rate in 3 years of 40 elderly patients treated by micro-transplants was 56.3%.There was no significant difference in the influence of age,risk prognosis grading,HLA matching,donor gender on micro-transplant recurrence.(P>0.05).Conclusion:1.AML is the most common malignant hematological disease in the elderly.Micro-transplantation is superior to traditional treatment in the treatment of elderly AML,induction remission rate and 3-year survival rate.It can be used as an important method for induction and post-remission treatment of elderly AML patients.2.Different age,risk stratification,HLA matching,and donor gender had no significant effect on leukocyte and platelet recovery time after micro-transplantation,but may have an effect on DFS and OS time.DFS and OS time had a tend to decrease when the age is high,the risk stratification is high,the HLA matching is not the same,and the donor and the recipient are the same gender(especially female for female).Further enlargement of sample size can make the difference more obvious.3.Dosages of CD34~+and CD3~+cells have effects on hematopoietic recovery after micro-transplantation,especially in the induction course.The hematopoietic recovery is faster in patients with CD34~+lymphocyte infusion larger than 1.55 x 10^6/kg and the hematopoietic recovery is tend to be faster in patients with CD3~+lymphocyte infusion larger than 0.74x 10^8/kg.Further enlargement of sample size can make the difference more obvious.4.No GVHD-related complications occurred after micro-transplantation,and the incidence of severe infection is low.No infection-related deaths and other complication were observed.5.Micro-transplantation for the treatment of elderly AML still faces the problem of high recurrence rate. |
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