伴白细胞计数异常的B细胞非霍奇金淋巴瘤临床特征及预后分析

doi:10.3969/j.issn.1006-7795.2018.03.004

摘要/Abstract

摘要： 目的探讨初诊时伴有白细胞（white blood cell，WBC）计数异常的B细胞非霍奇金淋巴瘤（B-cell non-Hodgkin lymphoma，B-NHL）患者的临床特征及治疗方案，评价疗效，分析生存情况。方法回顾性分析2011年1月至2017年12月就诊于山西医科大学第二医院伴有白细胞计数异常（WBC>10×10⁹/L或<4×10⁹/L）的B-NHL患者临床资料，根据白细胞计数异常程度分为3组：白细胞计数明显增高组（WBC>30×10⁹/L）、轻度增高组（WBC 10~30×10⁹/L）、减低组（WBC<4×10⁹/L），总结患者临床特点、治疗方案，评价早期治疗效果及生存情况，分析预后相关因素。结果 68例伴有白细胞计数异常的B-NHL，白细胞计数明显增高13例，轻度增高26例，减低29例；其中位就诊年龄63（19~80）岁，自出现症状至诊断的中位时间为2（0.2~120）个月，男女性别比为1.4：1。病理亚型以边缘区B细胞淋巴瘤（marginal zone B-cell lymphoma，MZL）、弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma，DLBCL）为主；分期均为Ⅲ/Ⅳ期或白血病期。有B症状者占57%（39/68）、乳酸脱氢酶（lactate dehydrogenase，LDH）升高者占54%（32/59），伴贫血和/或血小板减少占67.7%（46/68），淋巴细胞百分比增高者占56.7%（38/68），骨髓侵犯达91.7%（55/60），伴骨髓纤维化者占28%（15/53）。评价早期疗效40例，完全缓解（complete response，CR）率为17.5%（7/40），总反应率（overall response rate，ORR）为55.0%（22/40）；ORR与LDH、血小板计数、首次治疗后骨髓改善情况相关（P=0.028，P=0.048，P=0.031）。随访截至2018年1月31日，有效随访43例，中位随访时间22（1~70）个月，中位生存期（overall survival，OS）为24个月（95% CI：8.722~39.278），无进展生存期（progression-free survival，PFS）为13个月（95% CI：2.721~23.279），轻度增高组PFS优于其他两组（P1=0.017，P2=0.026）。单因素分析，侵袭性组织学、B症状、贫血、血小板减少、治疗方案、治疗后能否早期达CR或PR是OS的预后因素；LDH、白细胞分组、是否治疗、治疗后能否早期达CR或PR为PFS的影响因素。多因素分析，B症状为OS的影响因素，治疗后能否早期达CR或PR是OS、PFS的共同影响因素。结论伴有白细胞计数异常的B-NHL患者早期就诊率高，但分期均晚，大多数患者出现骨髓侵犯，常合并贫血、血小板减少。该类患者早期ORR低、整体PFS短，白细胞计数轻度增高患者的PFS较好，OS有待进一步观察；早期ORR是OS、PFS的影响因素。白血病期患者接受急性淋巴细胞白血病诱导强化方案治疗可获得较高的ORR。

关键词: B细胞非霍奇金淋巴瘤, 白细胞计数, 骨髓侵犯, 无进展生存, 总生存

Abstract: Objective To raise our understanding of B-cell non-Hodgkin lymphoma (B-NHL) patients with an abnormal leukocyte count at diagnosis, by summarizing and analyzing the characteristics and prognosis.Methods Retrospective analysis was performed on B-NHL patients with an abnormal leukocyte count in the initial diagnosis who were seen during January, 2011 to December, 2017;the clinical features,routine laboratory tests,bone marrow examinations,early responses were summarized. Overall survival (OS) and progression-free survival (PFS) were assessed and analyzed for factors that may affect the clinical prognosis.Results The median age of 68 patients was 63 (19-80) years. Marginal zone B-cell lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL) were the most common pathological subtypes. The Ann Arbor stage was in Ⅲ/IV stage or leukemic phase. Patients accompanied with anemia and/or thrombocytopenia accounted for 67.7%(46/68). The proportion of bone marrow involvement patients was 91.7% (55/60). Of 53 patients, 15 (28%) were accompanied with myelofibrosis; 40 patients were eligible for early response assessment,CR rate was 17.5%(7/40),and ORR was 55.0% (22/40). It was associated with the increased LDH, platelet count in the initial diagnosis and the improvement of bone marrow after the first treatment at early efficacy evaluation. Forty-three patients were followed up to January, 2018, the median follow-up time was 22 (1-70) months, the median PFS and OS were 13 (95% CI:2.721-23.279) months and 24 (95% CI:8.722-39.278) months, respectively. In a multivariate analysis, B-symptoms were the factors of OS, either CR or PR obtained through early treatment affected OS and PFS.Conclusion B-NHL with an abnormal leukocyte count had late phase,they often had B-symptoms and abnormal LDH. Bone marrow involvement was common in most patients,they were often found anemia and thrombocytopenia. A few patients achieved CR or PR after early treatment, they often had a short PFS. So further studies regarding long-term outcomes are required. Either CR or PR achieved through early treatment affected OS and PFS. Patients with leukemic phase could achieve better CR or PR if given ALL-intensive therapy,and more studies are needed.

Key words: B-cell non-Hodgkin lymphoma, leukocyte count, bone marrow involvement, progression-free survival, overall survival

中图分类号:

R557

王琨, 张建华, 张睿娟, 董春霞, 马小雯, 申星, 陈昆, 常舒婷, 杨林花. 伴白细胞计数异常的B细胞非霍奇金淋巴瘤临床特征及预后分析[J]. 首都医科大学学报, 2018, 39(3): 327-334.

Wang Kun, Zhang Jianhua, Zhang Ruijuan, Dong Chunxia, Ma Xiaowen, Shen Xing, Chen Kun, Chang Shuting, Yang Linhua. Clinical characteristics and prognosis of B-cell non-Hodgkin lymphoma with abnormal leukocyte count[J]. Journal of Capital Medical University, 2018, 39(3): 327-334.

参考文献

[1] Sehn L H, Berry B, Chhanabhai M, et al. The revised International prognostic index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP[J]. Blood, 2007, 109(5):1857-1861.
[2] Wang J, Zhou X, Liu Y, et al. Prognostic significance of neutrophil-to-lymphocyte ratio in diffuse large B-cell lymphoma:A meta-analysis[J]. PLoS One, 2017, 12(4):e0176008.
[3] Swerdlow S H, Campo E, Pileri S A, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms[J].Blood,2016, 127(20):2375-2390.
[4] 中国抗癌协会血液肿瘤专业委员会,中华医学会血液学分会白血病淋巴瘤学组,中国成人急性淋巴细胞白血病诊断与治疗指南(2016年版)[J]. 中华血液学杂志,2016,37(10):837-845.
[5] Al-Hamadani M, Habermann T M, Cerhan J R, et al. Non-Hodgkin lymphoma subtype distribution, geodemographic patterns, and survival in the US:A longitudinal analysis of the National Cancer Data Base from 1998 to 2011[J]. Am J Hematol, 2015, 90(9):790-795.
[6] Intragumtornchai T, Bunworasate U, Wudhikarn K, et al. Non-hodgkin lymphoma in south east asia:an analysis of the histopathology, clinical features, and survival from Thailand[J]. Hematol Oncol, 2018, 36(1):28-36.
[7] Xin X, Liu Z, Meng F, et al. Analysis of prognostic factors in lymphoma patients with bone marrow involvement:a single center cohort study[J]. Int J Clin Exp Med, 2015, (6):9676-9683.
[8] Bain B J, Catovsky D. The leukaemic phase of non-Hodgkin's lymphoma[J]. J Clin Pathol, 1995, 48(3):189-193.
[9] Muringampurath-John D, Jaye D L, Flowers C R, et al. Characteristics and outcomes of diffuse large B-cell lymphoma presenting in leukaemic phase[J]. Br J Haematol, 2012, 158(5):608-614.
[10] Nishimura K, Ota R, Mikajiri Y, et al. Useful laboratory markers for the diagnosis of bone marrow involvement by malignant lymphoma[J]. Int J Lab Hematol, 2018,40(1):34-40.
[11] Sovani V, Harvey C, Haynes A P, et al. Bone marrow trephine biopsy involvement by lymphoma:review of histopathological features in 511 specimens and correlation with diagnostic biopsy, aspirate and peripheral blood findings[J]. J Clin Pathol, 2014, 67(5):389-395.
[12] Spivak J L. The anaemia of cancer:death by a thousand cuts[J]. Nat Rev Cancer, 2005, 5(7):543-555.
[13] Adams H J, de Klerk J M, Fijnheer R, et al. Prognostic value of anemia and C-Reactive protein levels in diffuse large B-Cell Lymphoma[J]. Clin Lymphoma Myeloma Leuk, 2015, 15(11):671-679.
[14] Hong J, Woo H S, Kim H, et al. Anemia as a useful biomarker in patients with diffuse large B-cell lymphoma treated with R-CHOP immunochemotherapy[J]. Cancer Sci, 2014, 105(12):1569-1575.
[15] Federico M, Bellei M, Marcheselli L, et al. Follicular lymphoma international prognostic index 2:a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project[J]. J Clin Oncol, 2009, 27(27):4555-4562.
[16] Ochi Y, Kazuma Y, Hiramoto N, et al. Utility of a simple prognostic stratification based on platelet counts and serum albumin levels in elderly patients with diffuse large B cell lymphoma[J]. Ann Hematol, 2017, 96(1):1-8.
[17] Montalbán C, Abraira V, Arcaini L, et al. Risk stratification for splenic marginal zone lymphoma based on haemoglobin concentration, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy:development and validation on 593 cases[J]. Br J Haematol, 2012, 159(2):164-171.
[18] Belotti A, Doni E, Bolis S, et al. Peripheral blood lymphocyte/monocyte ratio predicts outcome in follicular lymphoma and in diffuse large b-cell lymphoma patients in the rituximab era[J]. Clin Lymphoma Myeloma Leuk, 2015, 15(4):208-213.
[19] Jachiet V, Mekinian A, Carrat F, et al. Autoimmune manifestations associated with lymphoma:characteristics and outcome in a multicenter retrospective cohort study[J]. Leuk Lymphoma, 2018,59(6):1399-1405.
[20] 杨申淼, 江倩, 江滨, 等.伴血象异常的脾边缘区淋巴瘤的临床特点[J].中国实验血液学杂志, 2013,21(1):87-94.
[21] 杨小芸, 沈丽达,龙庭凤,等.1326例非霍奇金淋巴瘤临床病理特点分析[J].中华肿瘤防治杂志,2016,23(9):605-609,620.
[22] 李喆,谭晓虹,岑洪.局限期侵袭性非霍奇金淋巴瘤联合放化疗临床意义Meta分析[J].中华肿瘤防治杂志,2015,22(11):885-890.
[23] 张丽娟,周静,王林,等.一项来自中国的单中心研究:18例原发性卵巢非霍奇金淋巴瘤的临床特征、治疗及预后分析[J].中国医科大学学报,2015,44(11):1024-1030.
[24] Stopeck A T, Unger J M, Rimsza L M, et al. A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma:SWOG 0515[J]. Blood, 2012, 120(6):1210-1217.
[25] Rezvani A R, Maloney D G. Rituximab resistance[J]. Best Pract Res Clin Haematol, 2011, 24(2):203-216.
[26] Wilson W H, Jung S H, Porcu P, et al. A Cancer and Leukemia group B multi-center study of DA-EPOCH-rituximab in untreated diff use large B-cell lymphoma with analysis of outcome by molecular subtype[J]. Haematologica, 2012, 97(5):758-765.
[27] Molina T J, Canioni D, Copie-Bergman C, et al. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab:analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase Ⅲ trial LNH 03-2B[J]. J Clin Oncol, 2014, 32(35):3996-4003.
[28] Nowakowski G S, LaPlant B, Macon W R, et al. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma:a phase Ⅱ study[J]. J Clin Oncol, 2015, 33(3):251-257.
[29] Arcaini L, Rossi D, Paulli M. Splenic marginal zone lymphoma:from genetics to management[J]. Blood, 2016; 127(17):2072-2081.