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血液或骨髓移植后皮肤恶性肿瘤的发病率及危险因素

Incidence of and Risk Factors for Cutaneous Malignant Neoplasms After Blood or Marrow Transplant.

作者信息

Broman Kristy K, Meng Qingrui, Holmqvist Anna, Balas Nora, Richman Joshua, Landier Wendy, Hageman Lindsey, Ross Elizabeth, Bosworth Alysia, Te Hok Sreng, Hollenquest Britany, Wong F Lennie, Bhatia Ravi, Forman Stephen J, Armenian Saro H, Weisdorf Daniel J, Bhatia Smita

机构信息

University of Alabama at Birmingham, Birmingham.

Birmingham VA Medical Center, US Department of Veterans Affairs, Birmingham, Alabama.

出版信息

JAMA Dermatol. 2025 Mar 1;161(3):265-273. doi: 10.1001/jamadermatol.2024.5129.

Abstract

IMPORTANCE

Cutaneous malignant neoplasms are the most common subsequent neoplasm after blood or marrow transplant (BMT), but a full assessment among survivors is lacking.

OBJECTIVE

To identify risk factors for subsequent cutaneous malignant neoplasms using the BMT Survivor Study (BMTSS).

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients who underwent transplant from 1974 to 2014 at City of Hope, University of Minnesota, or University of Alabama at Birmingham and survived 2 years or longer, as well as a comparison cohort of siblings. Both groups completed the BMTSS survey. Data analysis took place from October 2022 to October 2024.

EXPOSURES

Demographics, pre-BMT and BMT-related therapeutic exposures, chronic graft-vs-host disease (cGVHD), and posttransplant immunosuppression.

MAIN OUTCOMES AND MEASURES

Incident cutaneous malignant neoplasms (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) after BMT. Exposures were evaluated for association with subsequent neoplasms using proportional subdistribution hazards models (reported as subdistribution hazard ratio [SHR] and 95% CI).

RESULTS

Among the 3880 BMT survivors (median [range] age at BMT, 44.0 [0-78.0] years; 2165 [55.8%] male; 190 [4.9%] Black, 468 [12.1%] Hispanic, 2897 [74.7%] non-Hispanic White, and 325 [8.4%] of other race [including Asian and Pacific Islander] and multiracial) who were followed up for a median (range) of 9.5 (2.0-46.0) years, 605 developed 778 distinct cutaneous neoplasms (BCC, 321; SCC, 231; melanoma, 78; and unknown type, 148). The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% (BCC, 18.0%; SCC, 9.8%; and melanoma, 3.7%). Seventy-year cumulative probabilities of BCC, SCC, and melanoma were considerably higher in BMT survivors than siblings (18.1% vs 8.2%, 14.7% vs 4.2%, and 4.2% vs 2.4%, respectively). Among BMT survivors, risk factors for subsequent cutaneous malignant neoplasms included age of 50 years and older at BMT (BCC: SHR, 1.76; 95% CI, 1.36-2.29; SCC: SHR, 3.37; 95% CI, 2.41-4.72), male sex (BCC: SHR, 1.39; 95% CI, 1.10-1.75; SCC: SHR, 1.85; 95% CI, 1.39-2.45), pre-BMT monoclonal antibody exposure (BCC: SHR, 1.71; 95% CI, 1.27-2.31), allogeneic BMT with cGVHD (BCC: SHR, 1.48; 95% CI, 1.06-2.08; SCC: SHR, 2.61; 95% CI, 1.68-4.04 [reference: autologous BMT]), post-BMT immunosuppression (BCC: SHR, 1.63; 95% CI, 1.24-2.14; SCC: SHR, 1.48; 95% CI, 1.09-2.02; melanoma: SHR, 1.90; 95% CI, 1.16-3.12), and transplant at City of Hope (BCC: SHR, 3.55; 95% CI, 2.58-4.89; SCC: SHR, 3.57; 95% CI, 2.34-5.47 [reference: University of Minnesota]) or University of Alabama at Birmingham (BCC: SHR, 2.35; 95% CI, 1.35-4.23; SCC: SHR, 2.63; 95% CI, 1.36-5.08 [reference: University of Minnesota]). Race and ethnicity other than non-Hispanic White were protective for BCC (Black: no cases; Hispanic: SHR, 0.27; 95% CI, 0.16-0.44; other race and multiracial: SHR, 0.26; 95% CI, 0.14-0.50 [reference: non-Hispanic White]) and SCC (Black: SHR, 0.17; 95% CI, 0.04-0.67; Hispanic: SHR, 0.28; 95% CI, 0.16-0.50; other race and multiracial: SHR, 0.13; 95% CI, 0.05-0.37 [reference: non-Hispanic White]). Total body irradiation was associated with BCC risk among those younger than 50 years at BMT (SHR, 1.92; 95% CI, 1.27-2.92).

CONCLUSIONS AND RELEVANCE

In this cohort study, the high risk of cutaneous malignant neoplasms and malignant-specific risk factors suggest a need for personalized patient counseling and posttransplant dermatologic surveillance.

摘要

重要性

皮肤恶性肿瘤是血液或骨髓移植(BMT)后最常见的继发性肿瘤,但缺乏对幸存者的全面评估。

目的

利用BMT幸存者研究(BMTSS)确定继发性皮肤恶性肿瘤的危险因素。

设计、背景和参与者:这项回顾性队列研究纳入了1974年至2014年在希望之城、明尼苏达大学或阿拉巴马大学伯明翰分校接受移植且存活2年或更长时间的患者,以及一个同胞对照队列。两组均完成了BMTSS调查。数据分析于2022年10月至2024年10月进行。

暴露因素

人口统计学、移植前和与移植相关的治疗暴露、慢性移植物抗宿主病(cGVHD)以及移植后免疫抑制。

主要结局和测量指标

BMT后发生的皮肤恶性肿瘤(基底细胞癌[BCC]、鳞状细胞癌[SCC]和黑色素瘤)。使用比例亚分布风险模型评估暴露因素与继发性肿瘤的关联(报告为亚分布风险比[SHR]和95%CI)。

结果

在3880名BMT幸存者中(移植时的中位[范围]年龄为44.0[0 - 78.0]岁;2165名[55.8%]为男性;190名[4.9%]为黑人,468名[12.1%]为西班牙裔,2897名[74.7%]为非西班牙裔白人,325名[8.4%]为其他种族[包括亚洲和太平洋岛民]和多种族),中位(范围)随访9.5(2.0 - 46.0)年,605人发生了778种不同的皮肤肿瘤(BCC,321例;SCC,231例;黑色素瘤,78例;未知类型,148例)。任何皮肤恶性肿瘤的30年累积发病率为27.4%(BCC,18.0%;SCC,9.8%;黑色素瘤,3.7%)。BMT幸存者中BCC、SCC和黑色素瘤的70年累积概率显著高于同胞(分别为18.1%对8.2%、14.7%对4.2%和4.2%对2.4%)。在BMT幸存者中,继发性皮肤恶性肿瘤的危险因素包括移植时年龄在50岁及以上(BCC:SHR,1.76;95%CI,1.36 - 2.29;SCC:SHR,3.37;95%CI,2.41 - 4.72)、男性(BCC:SHR,1.39;95%CI,1.10 - 1.75;SCC:SHR,1.85;95%CI,1.39 - 2.45)、移植前单克隆抗体暴露(BCC:SHR,1.71;95%CI,1.27 - 2.31)、伴有cGVHD的异基因BMT(BCC:SHR,1.48;95%CI,1.06 - 2.08;SCC:SHR,2.61;95%CI,1.68 - 4.04[对照:自体BMT])、移植后免疫抑制(BCC:SHR,1.63;95%CI,1.24 - 2.14;SCC:SHR,1.48;95%CI,1.09 - 2.02;黑色素瘤:SHR,1.90;95%CI,1.16 - 3.12),以及在希望之城(BCC:SHR,3.55;95%CI,2.58 - 4.89;SCC:SHR,3.57;95%CI,2.34 - 5.47[对照:明尼苏达大学])或阿拉巴马大学伯明翰分校(BCC:SHR 2.35;95%CI,1.35 - 4.23;SCC:SHR,2.63;95%CI,1.36 - 5.08[对照:明尼苏达大学])进行移植。非西班牙裔白人以外的种族和族裔对BCC(黑人:无病例;西班牙裔:SHR,0.27;95%CI,0.16 - 0.44;其他种族和多种族:SHR,0.26;95%CI,0.14 - 0.50[对照:非西班牙裔白人])和SCC(黑人:SHR,0.17;95%CI,0.04 - 0.67;西班牙裔:SHR,0.28;95%CI,0.16 - 0.50;其他种族和多种族:SHR,0.13;95%CI,0.05 - 0.37[对照:非西班牙裔白人])具有保护作用。全身照射与移植时年龄小于50岁者的BCC风险相关(SHR,1.92;95%CI,1.27 - 2.92)。

结论与意义

在这项队列研究中,皮肤恶性肿瘤的高风险和特定恶性肿瘤的危险因素表明需要进行个性化的患者咨询和移植后皮肤监测。

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