| Background and ObjectiveAcute myeloid leukemia(AML)is a clinically and cytogenetically heterogeneous disease with diverse prognosis. The roles cytogenetics and genetic mutations played in prognosis prediction and risk classification are growing more and more import.Cytogenetic abnormality, which is closely to prognosis, can be detected in approximately 50%-60% of adult AML patients, including chromosome structural and numerical aberrations. Trisomy 8(+8) has been reported to be one of the most common numerical aberration in myeloid malignancies and is present in about 10% to 15% of all AML cases, either as the sole cytogenetic abnormality(+8 sole) or in combination with a large variety of different cytogenetic abnormalities. It is of great importance to clarify the prognostic impact of trisomy 8 in AML.To date, most researches about trisomy 8 AML mainly focused on the clinical presentation, treatment response and survival, while with controversial results. Although it has been reported that AML with trisomy 8 had similar prognosis to intermediate group, other results implied that AML patients with trisomy 8 had poor response to cytarabine-based chemotherapy and inferior outcome. Furthermore, limited informations on molecular genetics and impact of the additional chromosome abnormalities in trisomy 8 AML had been reported. In the present study,we examined the clinical and laboratory findings in 50 cases AML patients with trisomy 8 to determine the clinical characteristics of AMLwith trisomy 8. More importanly, the genecytic abnormalities and the impact of the additional chromosome abnormalities on trisomy 8 AML were also explored in our study. In addition,the clinical features of tretrasomy 8 and trisomy 8 with11q23 AML patients were also been studied. Material and methodsClinical and laboratory findings were examined in 519 patients in hematologic department of The First Affiliate Hospital of Zhengzhou University,including 50 cases with trisomy 8 divided into sole trisomy 8, trisomy 8 with additional abnormality, trisomy 8 with complex karyotype groups and 469 AML cases without trisomy 8,which classified into favorable, intermediate, adverse groups. The clinical features between the trisomy 8 groups and the non-trisomy 8 groups were compared retrospectively.The dates were analyzed by SPSS 17.0 software.All patients were followed up until January 31,2016 or the date of death or the date of lost to follow-up. Results1. Trisomy 8 was present in about 9.6%(50/519) of all adult AML,with 5%(26/519) as the sole abnormality.The median age was 43 years old and no statistical significance was found in sexural distribution. It was more often found in M5(46%) and M2(34%) in the FAB classification.2. When compared to non-trisomy 8 groups,in trisomy 8 patients,the WBC count and the percentage of peripheral blood blasts were significantly lower than those in adverse group(31.28 ± 37.78 × 109/L vs 68.35 ± 67.88 × 109/L,P <0.001;41.70±32.87% vs 60.49±33.39%,P=0.009). No significant differences in HBG, PLT, LDH,?2-MG, as well as extramedullary infiltration were found.3. By flowcytometry, blast cells in trisomy 8 AML frequently expressed CD58, CD38, CD33, HLA-DR, CD117, cMPO, CD123, but CD14 was less expressed.4. Molecular genetics evaluation revealed that AML with trisomy 8 always accompanied with genetic mutations predicting poor prognosis including TET2(92%),TP53(58%),ASXL1(33%),DNMT3a(22%),FLT3-ITD(20%),while genetic mutations with better prognosis such as NPM1(12%),IDH1(8%) were less frequent and no mutations in RUNX1 were detected.5. For AML patients with trisomy 8, the rate of total complete remission was 56%,which was significantly lower than that in favorable and intermediate groups(56% vs 98%,P<0.001;56% vs 90%,P<0.001),while compared with the adverse group,there was no statistical significance;the relapse rate was 29% in trisomy 8 AML, which was comparable to those in AML patients without trisomy 8.6. The median survival time and 2y-OS of trisomy 8 AML patients was 7 months and 30.1%, which were significantly lower than intermediate group(median survival:32months;2y-OS:54.8%,P=0.0012), there was no statistical significance when compared with the adverse group(median survival:8months;2y-OS:21.2%, P=0.4782).The 2y-RFS of trisomy 8 was 69.1%, when compared with the intermediate group(63.2%) and adverse group(46.4%),neither statistical significance were found.7. When compared the clinical presentation,genecytic feature and treatment response of each trisomy 8 groups,there was no statistical significance.The median survival and 2y-OS of sole trisomy 8, trisomy 8 with additional chromosome abnormality, trisomy 8 with complex karyotype,were 5.8 months and 20.8%, 19 months and 38.6%, 3.5months, respectively, with no statistical significance between each two trisomy 8 groups. But the survival curve of trisomy 8 suggested that the survival of sole trisomy 8 and trisomy 8 with complex karyotype had inferior effects on survival. The 2y-OS of trisomy 8 with 11q23 was 58.3%, which was better than that in AML patients with sole trisomy 8. ConclusionPatients with trisomy 8 have specific clinical features and often accompanied by genetic mutations indicating poor prognosis. The treatment response and outcome are poor. Additional karyotype has influences on the prognosis to some extent. |
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