慢性粒单核细胞白血病合并淋巴/浆细胞肿瘤9例临床分析

Chronic myelomonocytic leukemia patients co-occurrent with lymphoid/plasma cell neoplasms：a clinical analysis of 9 cases

摘要

目的: 描述慢性粒单核细胞白血病(chronic myelomonocytic leukemia，CMML)合并淋巴/浆细胞肿瘤患者的临床特征及预后情况。方法: 回顾性分析2016年1月—2025年8月于南京医科大学第一附属医院就诊的9例合并淋巴/浆细胞肿瘤的CMML(lymphoma/plasma cell neoplasms with CMML，LP-CMML)患者资料，并与年龄匹配的36例原发CMML(de novo CMML，DN-CMML)进行比较。结果: LP-CMML患者中位年龄66(58，76)岁，8例(88.9%)为男性，所有患者均为CMML-1，合并的淋巴/浆细胞肿瘤以弥漫大B细胞淋巴瘤最常见(3例)。LP-CMML与DN-CMML患者在基本临床特征、细胞遗传学风险分层及疾病危险分层分布上差异均无统计学意义。按照两种恶性肿瘤发生时序将患者分为治疗相关CMML(therapy related CMML，tCMML)4例，非tCMML 5例，tCMML患者较非tCMML更年轻(P=0.016)，且以发育异常型为主(P=0.048)。对1例tCMML患者进行动态基因检测显示，其在淋巴系统肿瘤诊断时即存在CMML前驱状态，并在病程中发生克隆演变。生存分析显示，LP-CMML患者中位总生存期(6个月 vs. 40个月，P<0.001)与中位无进展生存期(5个月 vs. 29个月，P<0.001)均显著短于DN-CMML患者，亚组分析示tCMML与非tCMML患者生存无显著差异。结论: LP-CMML患者存在临床异质性且预后不佳。

Abstract

Objective: To describe the clinical characteristics and prognosis of chronic myelomonocytic leukemia(CMML)patients co-occurrent with lymphoid/plasma cell neoplasms(LP-CMML). Methods: We retrospectively identified nine LP-CMML cases who visited the First Affiliated Hospital of Nanjing Medical University between January 2016 and August 2025，and compared their features with de novo CMML(DN-CMML). Results: The median age of LP-CMML patients was 66(58，76)years，with 8(88.9%)being male. All patients were classified as CMML-1. The most common co-existing lymphoid/plasma cell neoplasm was diffuse large B-cell lymphoma(3 cases). No differences were found between LP-CMML and DN-CMML in basic clinical characteristics，cytogenetic risk stratification and disease risk stratification. Based on the sequence of occurrence，4 patients were classified as therapy-related CMML(tCMML)and 5 as non-tCMML. Compared with the non-tCMML patients，tCMML patients were younger(P=0.016)and the dysplastic phenotype predominance(P=0.048). Dynamic monitoring of one tCMML patient revealed a pre-existing CMML precursor state at the time of lymphoid neoplasm diagnosis，with clonal evolution during the disease course. Survival analysis showed shorter median overall survivals(6 months vs. 40 months，P<0.001)and median progression free survivals(5 months vs. 29 months，P<0.001)for LP-CMML than those of DN-CMML. No difference was found in survivals between tCMML and non-tCMML subgroups. Conclusion: LP-CMML indicates clinical heterogeneity and poor survival.

关键词

慢性粒单核细胞白血病 / 淋巴/浆细胞肿瘤 / 临床特征 / 预后

Key words

chronic myelomonocytic leukemia / lymphoid/plasma cell neoplasms / clinical characteristics / prognosis

参考文献

[1] PATNAIK M M, TEFFERI A. Chronic myelomonocytic leukemia：2024 update on diagnosis，risk stratification and management[J]. American J Hematol, 2024, 99(6):1142-1165

[2] KHOURY J D, SOLARY E, ABLA O, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours：myeloid and histiocytic/dendritic neoplasms[J]. Leukemia, 2022, 36(7):1703-1719

[3] FERRY J A, HILL B, HSI E D. Mature B，T and NK—cell，plasma cell and histiocytic/dendritic cell neoplasms：classification according to the World Health Organization and International Consensus Classification[J]. J Hematol Oncol, 2024, 17(1):51

[4] ALKHATEEB H B, MOHTY R, GREIPP P, et al. Therapy—related myeloid neoplasms following chimeric antigen receptor T—cell therapy for non—Hodgkin lymphoma[J]. Blood Cancer J, 2022, 12(7):113

[5] NADIMINTI K, SIDIQI M H, MELEVEEDU K, et al. Characteristics and outcomes of therapy—related myeloid neoplasms following autologous stem cell transplantation for multiple myeloma[J]. Blood Cancer J, 2021, 11(3):63

[6] LIU Y, DERKACH A, LEWIS N, et al. Clonal hematopoiesis in diffuse large B—cell lymphoma：clinical impact and genetic relatedness to lymphoma and therapy—related myeloid neoplasm[J]. Haematologica, 2023, 108(3):917-922

[7] LI X, HUANG H, WANG F, et al. Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to DLBCL with CD19 CAR—T failure by single—cell RNA—seq[J]. Chin Med J(Engl), 2025, 138(15):1866-1881

[8] ALSULIMAN T, IKHLEF S, STOCKER N, et al. Coexistence of three hematological malignancies in association with a first time documented mutation：“One train can hide another”，and even more![J]. Curr Res Transl Med, 2023, 71(3):103403

[9] SUCH E, GERMING U, MALCOVATI L, et al. Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia[J]. Blood, 2013, 121(15):3005-3015

[10] ARBER D A, ORAZI A, HASSERJIAN R P, et al. International consensus classification of myeloid neoplasms and acute leukemias：integrating morphologic，clinical，and genomic data[J]. Blood, 2022, 140(11):1200-1228

[11] BATALLER A, GENER—RICOS G, ALMANZA—HUANTE E, et al. Therapy—related chronic myelomonocytic leukemia does not have the high—risk features of a therapy—related neoplasm[J]. Blood Adv, 2024, 8(11):2695-2706

[12] MCNERNEY M E, GODLEY L A, LE BEAU M M. Therapy—related myeloid neoplasms：when genetics and environment collide[J]. Nat Rev Cancer, 2017, 17(9):513-527

[13] MARANDO L, CSIZMAR C M, PATNAIK M M. Chronic myelomonocytic leukemia：molecular pathogenesis and therapeutic innovations[J]. Haematologica, 2025, 110(1):22-36

[14] LIU M C, ZHOU L Y, LIU Q X, et al. Clonal hematopoiesis of indeterminate potential(CHIP)and risk of non—Hodgkin lymphoma：a community—based cohort study[J]. Hema Sphere, 2025, 9(7):e70187

[15] TAKAHASHI K, PEMMARAJU N, STRATI P, et al. Clinical characteristics and outcomes of therapy—related chronic myelomonocytic leukemia[J]. Blood, 2013, 122(16):2807-2811

[16] SUBARI S, PATNAIK M, ALFAKARA D, et al. Patients with therapy—related CMML have shorter Median overall survival than those with de novo CMML：mayo clinic long—term follow—up experience[J]. Clin Lymphoma Myeloma Leuk, 2015, 15(9):546-549

[17] PATNAIK M M, VALLAPUREDDY R, YALNIZ F F, et al. Therapy related—chronic myelomonocytic leukemia(CMML)：molecular，cytogenetic，and clinical distinctions from de novo CMML[J]. American J Hematol, 2018, 93(1):65-73

[18] MARTIN P, CHEN Z M, CHESON B D, et al. Long—term outcomes，secondary malignancies and stem cell collection following bendamustine in patients with previously treated non—Hodgkin lymphoma[J]. Br J Haematol, 2017, 178(2):250-256

[19] SALEEM K, FRANZ J, KLEM M L, et al. Second primary malignancies in patients with haematological cancers treated with lenalidomide：a systematic review and meta—analysis[J]. Lancet Haematol, 2022, 9(12):e906-e918

基金资助

国家自然科学基金(82200151)