Effects Of Blood Recovery State At The Time Of Achieving Morphologic Complete Remission On Survival And Prognosis Of Patients With Acute Myeloid Leukemia

Background and ObjectivesAcute myeloid leukemia(AML)is a group of hematopoietic malignancies diseases originating from myeloid precursor cells.Patients with AML often exhibit fatigue,hemorrhage,infection,fever and other symptoms due to reduction of red blood cells,platelets,and functional leukocytes.It is known that the prognosis of AML patients is related to age,chromosome karyotype,molecular genetics and the number of white blood cells at the time of onset.With an age of?60 years,previous history of MDS or MPN,high white blood cell count(WBC?100×10~9/L),Treatment-related/secondary AML,CNSL,poor karyotypes or molecular genetic markers and induction therapy failed to achieve complete remission(CR)AML patients usually have poor prognosis.In addition,in recent years,foreign scholars found AML patients with blood recovery had better survival time compared with patients with poor blood recovery,when the initial bone marrow was completely relieved.In this study we analyzed the clinical features and prognosis of AML patients with poor blood recovery(PLT<100×10~9/L or ANC<1.0×10~9/L)during primary bone marrow complete remission in the First Affiliated Hospital of Zhengzhou University,and explore the value of poor blood recovery in the initial bone marrow complete remission on the prognosis of AML.MethodsA total of 302 AML patients with morphologic complete remission after chemotherapy in the First Affiliated Hospital of Zhengzhou University were analyzed restrospectivel.According to the condition of blood recovery when the bone marrow was completely resuscitated for the first time,they were divided into CR group(PLT?100×10~9/L and ANC?1.0×10~9/L)and CRi group(PLT<100×10~9/L or ANC<1.0×10~9/L),and the clinical characteristics and prognosis differences between the two groups were compared.We used SPSS21.0 software for statistical analysis.The general clinical characteristics of the two groups were compared by Kruskal-Wallis non-parametric tests.The rates were compared by chi-square test and Kaplan-Meier method for survival analysis.The recurrence rate,OS rate,DFS rate were analysed by Log-rank test,and multivariate analysis by COX regression model.P<0.05 was considered statistically significant.Results1.General clinical features:There are no statistics on sex,age,high white blood cells at the time of attendance,proportion of peripheral blood progenitors,percentage of bone marrow blasts,FAB type,NCCN chromosomal stratification,and FLT3/NPM1 gene mutation on CR and CRi groups(P?0.05).However,the proportion of patients with induction therapy?2 cycles in the CR group(25.6%)was lower than that in the CRi group(39.8%)(~2x=5.203,P=0.012).The proportion of MRD positive patients at the first time complete bone marrow complete remission in the CR group(39.8%)was lower than that in the CRi group(47.7%)(~2x=11.092,P=0.004),and the proportion of patients with myeloproliferative activity at the time of complete bone marrow complete remission in the CR group(84.3%)was higher than that in the CRi group(66.2%)(~2x=10.981,P=0.001).These differences were statistically significant.2.Overall efficacy:A total of 302 AML cases were followed up for 16(2 to 88)months.The 3-year recurrence rate,DFS and OS rates in CR group were 47.1%,36.2%,and 49.6%,and CRi group were69.9%,25.3%,and 32.7%.The 5-year recurrence rate,DFS rate and OS rate in CR group were 52.9%,32.3%,and43.0%,and CRi group were 78.5%,16.9%,and 32.7%.The relapse rate,DFS and OS rate in the two groups were statistically significant(P=0.003,P=0.040,P=0.002).3.Analysis of Recurrence and Survival Heterogeneity in CRi Patients:Univariate analysis and COX regression analysis were performed on CRi patients with complete hemorrhage at the time of initial bone marrow recovery.Induction therapy?2 courses(HR=2.453,95%CI 1.304~4.615,P=0.005),uncomplete recovery of peripheral blood neutrophil(HR=2.530,95%CI1.297~4.936,P=0.006),High-risk karyotype(HR=1.842,95%CI 1.148~2.955,P=0.011)were independent risk factors for relapse rate.Peripheral blood progenitor cells?60%(HR=1.826,95%CI 1.008~3.307,P=0.047),induction therapy?2 courses(HR=2.239,95%CI 1.203~4.166,P=0.011),primary bone marrow Peripheral blood neutrophils unrecovery(HR=2.220,95%CI 1.161~4.246,P=0.016)and high-risk karyotype(HR=2.079,95%CI 1.305~3.312,P=0.002)independent risk factors for DFS rate.FLT3 gene mutation positive(HR=5.445,95%CI 2.260~13.120,P<0.001),induction therapy?2 courses(HR=2.536,95%CI 1.294~4.973,P=0.007),peripheral blood neutrophils unrecovery(HR=2.056,95%CI 1.007~4.196,P=0.048)and high-risk karyotype(HR=1.639,95%CI 1.037~2.589,P=0.034)were independent risk factors that affected overall rate.Conclusions1.The proportion of patients with induction therapy?2 courses and MRD at the time of bone marrow complete remission in CRi patients were higher than that in CR patients,which indicates that CRi AML patients maybe have higher residual leukemia than CR patients.2.The 3-year and 5-year OS rates and DFS rates in CRi patients were significantly lower than that in CR patients.More over,3-year and 5-year recurrence rates CRi patients were significantly higher than CR patients,suggesting that CRi is one of the poor prognostic factors of AML.3.Poor recovery of neutrophils at the initial complete remission of bone marrow is one of the independent risk factors affecting prognosis of CRi AML,suggesting that neutrophil unrecovery AML patients should be regarded as high-risk group and consider more aggressive treatment.