18例儿童系统性ALK阳性间变大细胞淋巴瘤的临床特征及患儿预后分析
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摘要
目的:分析儿童间变大细胞淋巴瘤(ALCL)的临床特征,探讨治疗效果及预后因素。方法:收集2011年4月至2017年11月期间在福建医科大学附属协和医院小儿血液科收治的18例ALCL的临床、实验室及病理资料进行总结分析。结果:男女比例为2∶1,中位发病年龄6(0.9-11.3)岁,B症状阳性13例,17例首发症状为淋巴结肿大,所有病例伴有多部位受累。4例临床分期Ⅱ期,11例临床分期Ⅲ期,3例Ⅳ期。9例白细胞数增高,CRP>20 mg/L的8例,病理结果均为ALK阳性的间变大细胞淋巴瘤,Ki-67在40%-90%之间。2例在治疗前死亡,1例失访。15例采用CCCG-BNHL-2011方案化疗,中位随访时间41个月,2例早期复发,3年无事件生存率(76.7±10.2)%。Kaplan-Meier生存分析显示,白细胞数增多、CRP水平增高、骨质受累、临床分期对生存的影响具有统计学意义。结论:ALCL是儿童非霍奇金淋巴瘤一个较少见的亚型,疾病的侵袭性强。白细胞数增多、CRP水平增高、骨质受累、临床分期是影响预后的不良因素。
Objective: To analyze the clinical features and to explore the therapeutic efficacy and prognostic factors of children with anaplastic large cell lymphoma(ALCL). Methods: The clinical data of Pediatric Hematology, Union Hospital of Fujian Medical University fr1 o8 children with ALCL admitted in Department of m April w Results: The male to female ratio was 2011 to November 2017 as collected and analyzed. in 2∶1, the median age of onset was, and the B symptom was positive6(0.9-11.3) years old13 cases. The most common initial symptom was lymphadenopathy(in were manifested with multiple organ involvements. 17 cases). All patients 4 cases were classified as clinical stage Ⅱ, 11 cases as stage Ⅲ, and The pathol3 cases as stage Ⅳ. Laboratory tests revealed ogical results showed all ALK-positive anap9 cases with leukocytosis and lastic large cell lymphoma wit8 cases with CRP >h Ki-20 mg/L.ollow-up time was 67 rate between 40%-90%. The median fapy protoco4 l1 months. of CCCG-2 patients died before treatment, BNHL-1 patient was lost to follow-up. p15 atients accepted chemothersurvival analysis s2 h0 o1 w1. ed2 patients relapsed early, the leukocytosis, increased CRP3 year event-free survival rate was(76.7±10.2)%. Kaplan-Meier level, bone involvement and clinical stage were factors affecting prognosis. Conclusion: ALCL is a relatively rare subtype of childhood non-Hodgkin's lymphoma with high invasiveness. Leukocytosis, increased CRP level, bone involvement and clinical stage are poor factors affecting the prognosis of patients.
Objective: To analyze the clinical features and to explore the therapeutic efficacy and prognostic factors of children with anaplastic large cell lymphoma(ALCL). Methods: The clinical data of Pediatric Hematology, Union Hospital of Fujian Medical University fr1 o8 children with ALCL admitted in Department of m April w Results: The male to female ratio was 2011 to November 2017 as collected and analyzed. in 2∶1, the median age of onset was, and the B symptom was positive6(0.9-11.3) years old13 cases. The most common initial symptom was lymphadenopathy(in were manifested with multiple organ involvements. 17 cases). All patients 4 cases were classified as clinical stage Ⅱ, 11 cases as stage Ⅲ, and The pathol3 cases as stage Ⅳ. Laboratory tests revealed ogical results showed all ALK-positive anap9 cases with leukocytosis and lastic large cell lymphoma wit8 cases with CRP >h Ki-20 mg/L.ollow-up time was 67 rate between 40%-90%. The median fapy protoco4 l1 months. of CCCG-2 patients died before treatment, BNHL-1 patient was lost to follow-up. p15 atients accepted chemothersurvival analysis s2 h0 o1 w1. ed2 patients relapsed early, the leukocytosis, increased CRP3 year event-free survival rate was(76.7±10.2)%. Kaplan-Meier level, bone involvement and clinical stage were factors affecting prognosis. Conclusion: ALCL is a relatively rare subtype of childhood non-Hodgkin's lymphoma with high invasiveness. Leukocytosis, increased CRP level, bone involvement and clinical stage are poor factors affecting the prognosis of patients.
引文
1 Stein H,Mason DY,Gerdes J,et al.The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue:evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells.Blood,1985;66(4):848-858.
2 O'Connor NT,Stein H,Gatter KC,et al.Genotypic analysis of large cell lymphomas which express the Ki-1 antigen.Histopathology,1987;11(7):733-740.
3 Herbst H,Tippelmann G,Anagnostopoulos I,et al.Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma:dissociation between phenotype and genotype.Leuk Res,1989;13(2):103-116.
4 Muwhy SB.Classification,staging and results of treatment of childhood non-Hodgkin's lymphomas:dissimilarities from lymphoma as in adults.Semin Oncol,l980;7(3):332-339.
5中华医学会儿科学分会血液学组,中国抗癌协会儿科专业委员会,《中华儿科杂志》编辑委员会.儿童非霍奇金淋巴瘤诊疗建议.中华儿科杂志,2011;49(3):186-192.
6马肖容,徐燕,王瑾,等.254例非霍奇金淋巴瘤的临床疗效与预后分析.中国实验血液学杂志,2016;24(4):1044-1050.
7 Jaglowski SM,Linden E,Termuhlen AM,et al.Lymphoma in adolescents and young adults.Semin Oncol,2009;36(5):381-418.
8 Swerdlow SH,Campo E,Pileri SA,et al.The 2016 revision of the World Health Organization classification of lymphoid neoplasms.Blood,2016;127(20):2375-2390.
9 Burkhardt B,Zimmermann M,Oschlies I,et al.The impact of age and gender on biology,clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence.Br JHaematol,2005;131(1):39-49.
10杨艳丽,高子芬,周春菊,等.原发系统型间变性大细胞淋巴瘤56例临床特征和预后相关因素分析.白血病·淋巴瘤,2008;17(3):178-181.
11叶启东,汤静燕,潘慈,等.儿童间变性大细胞淋巴瘤20例临床疗效分析.中国小儿血液与肿瘤杂志,2012;17(1):13-16.
12杨菁,金玲,郑胡镛,等.儿童间变性大细胞淋巴瘤38例临床特征及疗效观察.中华儿科杂志,2012;50(3):223-226.
13 Le Deley MC,Reiter A,Williams D,et al.Prognostic factors in childhood anaplastic large cell lymphoma:results of a large European intergroup study.Blood,2008;111(3):1560-1566.
14 Damm-Welk C,Busch K,Burkhardt B,et al.Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK-positive anaplastic large cell lymphoma.Blood,2007;110(2):670-677.
15 Mussolin L,Damm-Welk C,Pillon M,et al.Use of minimal disseminated disease and immunity to NPM-ALK antigen to stratify ALK-positive ALCL patients with different prognosis.Leukemia,2013;27(2):416-422.
16 Ait-Tahar K,Damm-Welk C,Burkhardt B,et al.Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor dissemination and relapse risk.Blood,2010;115(16):3314-3319.
17 Mussolin L,Bonvini P,Ait-Tahar K,et al.Kinetics of humoral response to ALK and its relationship with minimal residual disease in pediatric ALCL.Leukemia,2009;23(2):400-402.
18 Mellgren K,Hedegaard CJ,Schmiegelow K,et al.Plasma cytokine profiles at diagnosis in pediatric patients with non-Hodgkin lymphoma.J Pediatr Hematol Oncol,2012;34(4):271-275.
19 Kn?rr F,Damm-Welk C,Ruf S,et al.Blood cytokine concentrations in pediatric patients with anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.Haematologica,2018;103(3):477-485.
20 Rosolen A,Pillon M,Garaventa A,et al.Anaplastic large cell lymphoma treated with a leukemia-like therapy:report of the Italian Association of Pediatric Hematology and Oncology(AIEOP)LNH-92 protocol.Cancer,2005;104(10):2133-2140.
21 Le Deley MC,Rosolen A,Williams DM,et al.Vinblastine in children and adolescents with high-risk anaplastic large cell lymphoma:results of the randomized ALCL99-vinblastine trial.JClin Oncol,2010;28(25):3987-3993.
22中华医学会儿科学分会血液学组淋巴瘤协作组,中国抗癌协会小儿肿瘤专业委员会淋巴瘤协作组.儿童间变大细胞淋巴瘤多中心诊治情况调查研究.中华儿科杂志,2017;55(3):194-199.
23 Minard-Colin V,Brugières L,Reiter A,et al.Non-Hodgkin lymphoma in children and adolescents:progress through effective collaboration,current knowledge,and challenges ahead.J Clin Oncol,2015;33(27):2963-2974.
24 Brugieres L,Pacquement H,Le Deley MC,et al.Single-drug vinblastine as salvage treatment for refractory or relapsed anaplastic large-cell lymphoma:a report from the French Society of Pediatric Oncology.J Clin Oncol,2009;27(30):5056-5061.
25 Woessmann W,Zimmermann M,Lenhard M,et al.Relapsed or refractory anaplastic large-cell lymphoma in children and adolescents after Berlin-Frankfurt-Muenster(BFM)-type first-line therapy:a BFM-group study.J Clin Oncol,2011;29(22):3065-3071.
26 Woessmann W,Peters C,Lenhard M,et al.Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents-a Berlin-Frankfurt-Munster group report.Br J Haematol,2006;133(2):176-182.
27 Pro B,Advani R,Brice P,et al.Brentuximab Vedotin(SGN-35)in patients with relapsed or refractory systemic anaplastic large cell lymphoma:results of a phase II study.J Clin Oncol,2012;30(18):2190-2196.
28 Mosse YP,Voss SD,Lim MS,et al.Targeting ALK with Crizotinib in pediatric anaplastic large cell lymphoma and inflammatory myofibroblastic tumor:a Children's Oncology Group study.J Clin Oncol,2017;35(28):3215-3221.
2 O'Connor NT,Stein H,Gatter KC,et al.Genotypic analysis of large cell lymphomas which express the Ki-1 antigen.Histopathology,1987;11(7):733-740.
3 Herbst H,Tippelmann G,Anagnostopoulos I,et al.Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma:dissociation between phenotype and genotype.Leuk Res,1989;13(2):103-116.
4 Muwhy SB.Classification,staging and results of treatment of childhood non-Hodgkin's lymphomas:dissimilarities from lymphoma as in adults.Semin Oncol,l980;7(3):332-339.
5中华医学会儿科学分会血液学组,中国抗癌协会儿科专业委员会,《中华儿科杂志》编辑委员会.儿童非霍奇金淋巴瘤诊疗建议.中华儿科杂志,2011;49(3):186-192.
6马肖容,徐燕,王瑾,等.254例非霍奇金淋巴瘤的临床疗效与预后分析.中国实验血液学杂志,2016;24(4):1044-1050.
7 Jaglowski SM,Linden E,Termuhlen AM,et al.Lymphoma in adolescents and young adults.Semin Oncol,2009;36(5):381-418.
8 Swerdlow SH,Campo E,Pileri SA,et al.The 2016 revision of the World Health Organization classification of lymphoid neoplasms.Blood,2016;127(20):2375-2390.
9 Burkhardt B,Zimmermann M,Oschlies I,et al.The impact of age and gender on biology,clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence.Br JHaematol,2005;131(1):39-49.
10杨艳丽,高子芬,周春菊,等.原发系统型间变性大细胞淋巴瘤56例临床特征和预后相关因素分析.白血病·淋巴瘤,2008;17(3):178-181.
11叶启东,汤静燕,潘慈,等.儿童间变性大细胞淋巴瘤20例临床疗效分析.中国小儿血液与肿瘤杂志,2012;17(1):13-16.
12杨菁,金玲,郑胡镛,等.儿童间变性大细胞淋巴瘤38例临床特征及疗效观察.中华儿科杂志,2012;50(3):223-226.
13 Le Deley MC,Reiter A,Williams D,et al.Prognostic factors in childhood anaplastic large cell lymphoma:results of a large European intergroup study.Blood,2008;111(3):1560-1566.
14 Damm-Welk C,Busch K,Burkhardt B,et al.Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK-positive anaplastic large cell lymphoma.Blood,2007;110(2):670-677.
15 Mussolin L,Damm-Welk C,Pillon M,et al.Use of minimal disseminated disease and immunity to NPM-ALK antigen to stratify ALK-positive ALCL patients with different prognosis.Leukemia,2013;27(2):416-422.
16 Ait-Tahar K,Damm-Welk C,Burkhardt B,et al.Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor dissemination and relapse risk.Blood,2010;115(16):3314-3319.
17 Mussolin L,Bonvini P,Ait-Tahar K,et al.Kinetics of humoral response to ALK and its relationship with minimal residual disease in pediatric ALCL.Leukemia,2009;23(2):400-402.
18 Mellgren K,Hedegaard CJ,Schmiegelow K,et al.Plasma cytokine profiles at diagnosis in pediatric patients with non-Hodgkin lymphoma.J Pediatr Hematol Oncol,2012;34(4):271-275.
19 Kn?rr F,Damm-Welk C,Ruf S,et al.Blood cytokine concentrations in pediatric patients with anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.Haematologica,2018;103(3):477-485.
20 Rosolen A,Pillon M,Garaventa A,et al.Anaplastic large cell lymphoma treated with a leukemia-like therapy:report of the Italian Association of Pediatric Hematology and Oncology(AIEOP)LNH-92 protocol.Cancer,2005;104(10):2133-2140.
21 Le Deley MC,Rosolen A,Williams DM,et al.Vinblastine in children and adolescents with high-risk anaplastic large cell lymphoma:results of the randomized ALCL99-vinblastine trial.JClin Oncol,2010;28(25):3987-3993.
22中华医学会儿科学分会血液学组淋巴瘤协作组,中国抗癌协会小儿肿瘤专业委员会淋巴瘤协作组.儿童间变大细胞淋巴瘤多中心诊治情况调查研究.中华儿科杂志,2017;55(3):194-199.
23 Minard-Colin V,Brugières L,Reiter A,et al.Non-Hodgkin lymphoma in children and adolescents:progress through effective collaboration,current knowledge,and challenges ahead.J Clin Oncol,2015;33(27):2963-2974.
24 Brugieres L,Pacquement H,Le Deley MC,et al.Single-drug vinblastine as salvage treatment for refractory or relapsed anaplastic large-cell lymphoma:a report from the French Society of Pediatric Oncology.J Clin Oncol,2009;27(30):5056-5061.
25 Woessmann W,Zimmermann M,Lenhard M,et al.Relapsed or refractory anaplastic large-cell lymphoma in children and adolescents after Berlin-Frankfurt-Muenster(BFM)-type first-line therapy:a BFM-group study.J Clin Oncol,2011;29(22):3065-3071.
26 Woessmann W,Peters C,Lenhard M,et al.Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents-a Berlin-Frankfurt-Munster group report.Br J Haematol,2006;133(2):176-182.
27 Pro B,Advani R,Brice P,et al.Brentuximab Vedotin(SGN-35)in patients with relapsed or refractory systemic anaplastic large cell lymphoma:results of a phase II study.J Clin Oncol,2012;30(18):2190-2196.
28 Mosse YP,Voss SD,Lim MS,et al.Targeting ALK with Crizotinib in pediatric anaplastic large cell lymphoma and inflammatory myofibroblastic tumor:a Children's Oncology Group study.J Clin Oncol,2017;35(28):3215-3221.