高超二倍体、三/四倍体染色体核型在急性髓细胞白血病中的预后意义
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摘要
目的描述高超二倍体、三/四倍体染色体核型急性髓细胞白血病(HH/TT-AML)患者的生物学特征,探讨其与预后的关系。方法回顾性分析2006年3月至2017年6月28例HH/TT-AML初治患者一般临床特征、治疗情况,用Kaplan-Meier方法分析预后影响因素。结果 HH/TT-AML患者核型以49条染色体为主,占39.3%(11/28),50～55条染色体次之,占32.1%(9/28)。高超二倍体核型急性髓细胞白血病(HH-AML)患者以+8(77.3%,17/22)、+21(54.5%,12/22)多见。生存分析显示,伴-5/5q-、-7/7q-、-17/der(17p)及der(3q)的HH/TT-AML患者总体生存率劣于不伴此类异常者(4.1月vs 10.1月,P<0.05);三/四倍体染色体核型急性髓细胞白血病(TT-AML)患者总体生存率与HH-AML患者差异无统计学意义(8.4月vs 7.2月,P>0.05);异基因造血干细胞移植患者总体生存率优于仅化疗患者(25.4月vs 4.1月,P<0.01)。结论 HH/TT-AML患者存在较大异质性,不良预后相关染色体异常的识别有助于预后分层。此类患者总体生存期短,联合化疗获缓解后尽早行异基因造血干细胞移植能显著改善患者预后。
Objective To investigate the biological characteristics of high hyperdiploid and triploid/tetraploid acute myeloid leukemia(HH/TT-AML) and its relationship with prognosis. Methods The clinical data of 28 patients with newly diagnosed HH/TT-AML during March 2006 and June 2017 were retrospectively analyzed, and the factors influencing prognosis were analyzed by the Kaplan-Meier method. Results The karyotypes of HH/TT-AML patients were mainly 49 chromosomes, accounting for 39.3%(11/28), followed by 50-55 chromosomes, accounting for 32.1%(9/28). The karyotypes of high hyperdiploid acute myeloid leukemia(HH-AML) patients were more likely to be +8(77.3%, 17/22) or +21(54.5%, 12/22). The survival analysis showed that the overall survival rate of HH/TT-AML patients with-5/5 q-,-7/7 q-,-17/der(17 p) or der(3 q) was significantly lower than that without these abnormalities(4.1 months vs 10.1 months,P<0.05). There was no significant difference in the overall survival rate between triploid/tetraploid acute myeloid leukemia(TT-AML) patients and HH-AML patients(8.4 months vs 7.2 months,P>0.05). The overall survival rate of the patients with allogeneic hematopoietic stem cell transplantation was significantly longer than that with chemotherapy alone(25.4 months vs 4.1 months,P<0.01). Conclusion HH/TT AML patients are highly heterogeneous. The identification of poor prognosis-related chromosome abnormalities is helpful for the stratification of prognosis. The overall survival time of these patients is short. Early allogeneic hematopoietic stem cell transplantation after remission by combination chemotherapy can significantly improve the prognosis of these patients.
Objective To investigate the biological characteristics of high hyperdiploid and triploid/tetraploid acute myeloid leukemia(HH/TT-AML) and its relationship with prognosis. Methods The clinical data of 28 patients with newly diagnosed HH/TT-AML during March 2006 and June 2017 were retrospectively analyzed, and the factors influencing prognosis were analyzed by the Kaplan-Meier method. Results The karyotypes of HH/TT-AML patients were mainly 49 chromosomes, accounting for 39.3%(11/28), followed by 50-55 chromosomes, accounting for 32.1%(9/28). The karyotypes of high hyperdiploid acute myeloid leukemia(HH-AML) patients were more likely to be +8(77.3%, 17/22) or +21(54.5%, 12/22). The survival analysis showed that the overall survival rate of HH/TT-AML patients with-5/5 q-,-7/7 q-,-17/der(17 p) or der(3 q) was significantly lower than that without these abnormalities(4.1 months vs 10.1 months,P<0.05). There was no significant difference in the overall survival rate between triploid/tetraploid acute myeloid leukemia(TT-AML) patients and HH-AML patients(8.4 months vs 7.2 months,P>0.05). The overall survival rate of the patients with allogeneic hematopoietic stem cell transplantation was significantly longer than that with chemotherapy alone(25.4 months vs 4.1 months,P<0.01). Conclusion HH/TT AML patients are highly heterogeneous. The identification of poor prognosis-related chromosome abnormalities is helpful for the stratification of prognosis. The overall survival time of these patients is short. Early allogeneic hematopoietic stem cell transplantation after remission by combination chemotherapy can significantly improve the prognosis of these patients.
引文
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[11]中华医学会血液学分会白血病淋巴瘤学组. 成人急性髓系白血病(非急性早幼粒细胞白血病)中国诊疗指南(2017年版)[J]. 中华血液学杂志, 2017, 38(3): 177-182.
[12]Iyer RV, Sait SN, Matsui S, et al. Massive hyperdiploidy and tetraploidy in acute myelocytic leukemia and myelodysplastic syndrome[J]. Cancer Genet Cytogenet, 2004, 148(1): 29-34.
[13]Huang L, Wang SA, DiNardo C, et al. Tetraploidy/near-tetraploidy acute myeloid leukemia[J]. Leuk Res, 2017, 53: 20-27.
[14]Pang CS, Pettenati MJ, Pardee TS. Clinicopathological analysis of near-tetraploidy/tetraploidy acute myeloid leukaemia[J]. J Clin Pathol, 2015, 68(3): 236-240.
[15]Luquet I, Lai JL, Barin C, et al. Hyperdiploid karyotypes in acute myeloid leukemia define a novel entity: a study of 38 patients from the Groupe Francophone de Cytogenetique Hematologique (GFCH)[J]. Leukemia, 2008, 22(1): 132-137.
[16]St?lze F, Mohr B, Kramer M, et al. Karyotype complexity and prognosis in acute myeloid leukemia[J]. Blood Cancer J, 2016, 6: e386.
[17]Bowen D, Groves MJ, Burnett AK, et al. TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis[J]. Leukemia, 2009, 23(1): 203-206.
[18]Rucker FG, Schlenk RF, Bullinger L, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome[J]. Blood, 2012, 119(9): 2114-2121.
[2]Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study[J]. Blood, 2000, 96(13): 4075-4083.
[3]von Neuhoff C, Reinhardt D, Sander A, et al. Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98[J]. J Clin Oncol, 2010, 28(16): 2682-2689.
[4]Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5 876 younger adult patients treated in the United Kingdom Medical Research Council trials[J]. Blood, 2010, 116(3): 354-365.
[5]Sandahl JD, Kjeldsen E, Abrahamsson J, et al. Ploidy and clinical characteristics of childhood acute myeloid leukemia: A NOPHO-AML study[J]. Genes chromosomes cancer, 2014, 53(8): 667-675.
[6]Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet[J]. Blood, 2010, 115(3): 453-474.
[7]Lazarevic V, Rosso A, Juliusson G, et al. Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia[J]. Am J Hematol, 2015, 90(9): 800-805.
[8]Chilton L, Hills RK, Harrison CJ, et al. Hyperdiploidy with 49-65 chromosomes represents a heterogeneous cytogenetic subgroup of acute myeloid leukemia with differential outcome[J]. Leukemia, 2014, 28(2): 321-328.
[9]Arber D A, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J]. Blood, 2016, 127(20): 2391-2405.
[10]Shaffer LG, McGowan-Jordan J, Schmid M. ISCN 2013: An international system for human cytogenetic nomenclature [M]. Switzerland: S.Karger AG, 2012: 1-140.
[11]中华医学会血液学分会白血病淋巴瘤学组. 成人急性髓系白血病(非急性早幼粒细胞白血病)中国诊疗指南(2017年版)[J]. 中华血液学杂志, 2017, 38(3): 177-182.
[12]Iyer RV, Sait SN, Matsui S, et al. Massive hyperdiploidy and tetraploidy in acute myelocytic leukemia and myelodysplastic syndrome[J]. Cancer Genet Cytogenet, 2004, 148(1): 29-34.
[13]Huang L, Wang SA, DiNardo C, et al. Tetraploidy/near-tetraploidy acute myeloid leukemia[J]. Leuk Res, 2017, 53: 20-27.
[14]Pang CS, Pettenati MJ, Pardee TS. Clinicopathological analysis of near-tetraploidy/tetraploidy acute myeloid leukaemia[J]. J Clin Pathol, 2015, 68(3): 236-240.
[15]Luquet I, Lai JL, Barin C, et al. Hyperdiploid karyotypes in acute myeloid leukemia define a novel entity: a study of 38 patients from the Groupe Francophone de Cytogenetique Hematologique (GFCH)[J]. Leukemia, 2008, 22(1): 132-137.
[16]St?lze F, Mohr B, Kramer M, et al. Karyotype complexity and prognosis in acute myeloid leukemia[J]. Blood Cancer J, 2016, 6: e386.
[17]Bowen D, Groves MJ, Burnett AK, et al. TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis[J]. Leukemia, 2009, 23(1): 203-206.
[18]Rucker FG, Schlenk RF, Bullinger L, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome[J]. Blood, 2012, 119(9): 2114-2121.