Changes Of Serum Copper,Zinc Levels And Copper/Zinc Ratio In Patients With Newly Diagnosed AML And Their Effects On Early Outcomes

Objective:We detected the levels of serum copper,zinc and copper-zinc ratios in patients with newly diagnosed acute myeloid leukemia in our center and evaluated the effect on early outcomes of different serum copper-zinc ratios in newly diagnosed adult patients with acute myeloid leukemia.Methods:In the first step,A total of 109 patients who were admitted to the Hematology Department of the First Hospital of Jilin University and newly diagnosed with devo acute myeloid leukemia from October 2017 to April 2019 were selected as the control group,and 82 healthy patients who underwent a physical examination at physical examination center of the First Hospital of Jilin University during the same period were selected as the control group.We collected the basic information,clinical data and serum samples of those patients,and used mass spectrometry to detect serum copper and zinc level.Then,we compared the differences in serum copper,zinc and copperzinc ratio between the two groups.In the second step,we collected the serum of 19 patients with acute myeloid leukemia after complete remission,and compared the differences in serum copper,zinc levels and copper/zinc ratio before and after complete remission in those patients.In the third step,88 patients with acute myeloid leukemia who had complete clinical data were concluded.We analyzed the relevant factors affecting serum copper,zinc levels and copper/zinc ratio.In the fourth stage,64 newly diagnosed adult acute myeloid leukemia patients under the age of 65 years who received standard chemotherapy were included,the effects of serum copper,zinc levels and copper/zinc ratio on early outcomes such as early death rate and first-round induction of complete remission rate were studied.Results:1.Compared to the healthy controls,there was statistically significant increasing in serum copper(P<0.001)and serum copper/zinc ratio(P<0.001),and statistically significant decreasing in serum zinc level(P<0.001)in case group.2.Comparing the serum copper,zinc,and copper/zinc ratio of 19 patients before and after complete remission,the results suggested that the serum copper and zinc levels of patients after complete remission had an upward trend compared with those before treatment,and the copper / zinc ratio had slightly decreased compared with before.But there was no statistical significance(P> 0.05).3.Univariate analysis suggested that related factors that affected serum copper levels in patients with acute myeloid leukemia included C-reactive protein(P=0.015),hemoglobin levels(P=0.021),and the ratio of blast cells in bone marrow(P=0.046).Multi-factor analysis suggested the proportion of bone marrow blasts(P=0.02)was a mainly relevant factor of serum copper level for patients with acute myeloid leukemia.Univariate analysis suggested that related factors that affected serum zinc levels in patients with acute myeloid leukemia included white blood cell counts(P=0.019),hemoglobin level(P=0.024),platelet counts(P=0.024)and albumin level(P=0.004),and multi-factor analysis suggested that the albumin level(P = 0.018)was a mainly relevant factor of serum zinc level for patients with acute myeloid leukemia.Univariate analysis suggested that related factors that affected serum copper/zinc ratio in patients with acute myeloid leukemia included body surface area(P=0.043),hemoglobin level(P<0.001),albumin level(P<0.001)and C-reactive protein(P=0.019),and multifactor analysis suggested that the albumin level(P = 0.019)and C-reactive protein(P=0.022)were mainly relevant factors of serum copper/zinc ratio for patients with acute myeloid leukemia.4.The serum copper/zinc ratio of 64 newly diagnosed adult patients with acute myeloid leukemia who were under 65 years of age receiving standard chemotherapy was compared to explore the effects on early outcomes.Using the ROC curve,the critical point of the copper / zinc ratio was 1.68.The patients were divided into two groups with high serum copper / zinc ratio and low serum copper / zinc ratio group.The results suggested that,high serum copper / zinc ratio patients had a worse genetic risk stratification(P = 0.010),a higher early death rate(P = 0.011),and a lower complete remission rate after 1 course of chemotherapy(P = 0.016).But there was no statistically significant difference in complete remission rate with MRD negative and complete remission rate after 2 courses of chemotherapy(P>0.05)between two groups.Conclusion:1.The serum levels of copper and zinc in patients with newly diagnosed acute myeloid leukemia had obvious abnormalities.Comparing to healthy controls,serum copper and copper / zinc ratios in patients with newly diagnosed acute myeloid leukemia were significantly higher and serum zinc levels were significantly lower.2.After achieving complete remission,the serum copper and zinc levels of patients had an upward trend compared with that before treatment,and the copper / zinc ratio had slightly decreased.3.Factors of serum copper in patients with acute myeloid leukemia included Creactive protein(P=0.015),hemoglobin level(P=0.021),and the ratio of blast cells in bone marrow(P=0.046),and the proportion of bone marrow blasts(P=0.02)was a mainly relevant factor of serum copper level for patients with acute myeloid leukemia.4.Factors of serum zinc in patients with acute myeloid leukemia included white blood cell counts(P=0.019),hemoglobin level(P=0.024),platelet counts(P=0.024),and albumin level(P=0.004),and the albumin level(P = 0.018)was an mainly relevant factor of serum zinc level for patients with acute myeloid leukemia.5.Factors of serum copper/zinc ratio in patients with acute myeloid leukemia included body surface area(P=0.043),hemoglobin level(P<0.001),albumin level(P<0.001)and C-reactive protein(P=0.019).The albumin level(P = 0.019)and Creactive protein(P=0.022)were mainly relevant factors of serum copper/zinc ratio for patients with acute myeloid leukemia.6.A high level of serum copper/zinc ratio may indicate a poor early outcomes for newly diagnosed adult acute myeloid leukemia patients.There were worse genetic risk stratification,higher early death rate and lower complete remission rate with one course of standard induction regimens in those patients.