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实体器官移植后成人PTLD一线治疗中R-EPOCH方案的回顾性评估

Retrospective evaluation of R-EPOCH in the frontline treatment of adult patients with PTLD after solid organ transplant.

作者信息

Cuzzo Brian, Ford Maegan, Jain Saagar, Cherng Hua-Jay, Orlando Evelyn, Gould Patrick, Song Amy, May Benjamin, Chen Yuxuan, Bhagat Govind, Lipsky Andrew H, Pro Barbara, Amengual Jennifer E

机构信息

Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY.

Pediatric Hematology-Oncology, Children's Hospital of New Jersey at Beth Israel Medical Center, Newark, NJ.

出版信息

Blood Neoplasia. 2025 Mar 10;2(2):100094. doi: 10.1016/j.bneo.2025.100094. eCollection 2025 May.

Abstract

Posttransplant lymphoproliferative disorders (PTLD) are rare complications of solid organ transplantation, which carry significant morbidity and mortality. Phase 2 trials that use sequential rituximab (R) followed by R, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) have become an acceptable approach for B-cell PTLD, although it carries a high risk of treatment-related mortality (up to 11%). Many aspects of B-cell PTLD biology and patient characteristics parallel AIDS-related lymphomas in which dose-modified R, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DM-R-EPOCH) has been demonstrated to be highly efficacious and safe. In this single-institution retrospective study of (N = 101) adult transplant recipients with B-cell PTLD, 65 received DM-R-EPOCH, 8 received R-CHOP, and 17 received R monotherapy. Median progression-free and overall survival was 4.4 years and 6.4 years, respectively, for DM-R-EPOCH and 1 year and 1.1 years, respectively, for R-CHOP. Rates of neutropenia and infection were 70% and 77%, respectively, for DM-R-EPOCH, and 88% each for R-CHOP. Treatment-related mortality for patients treated with DM-R-EPOCH and R-CHOP was 4.7% and 25%, respectively. The median number of cycles of DM-R-EPOCH was 6, and between 73% and 89% of patients received a relative dose intensity of ≥80% for cyclophosphamide, etoposide, and doxorubicin. The relative dose intensity of vincristine was <80% in 56% of patients because of frequent omission for gastrointestinal involvement of PTLD. Collectively, these data suggest that DM-R-EPOCH does not lead to excessive toxicity in patients with B-cell PTLD and support the need for further prospective clinical studies.

摘要

移植后淋巴细胞增生性疾病(PTLD)是实体器官移植的罕见并发症,具有显著的发病率和死亡率。采用序贯利妥昔单抗(R)继以R、环磷酰胺、多柔比星、长春新碱和泼尼松(R-CHOP)的2期试验已成为治疗B细胞PTLD的一种可接受方法,尽管其具有较高的治疗相关死亡率风险(高达11%)。B细胞PTLD生物学和患者特征的许多方面与艾滋病相关淋巴瘤相似,在艾滋病相关淋巴瘤中,剂量调整的R、依托泊苷、泼尼松、长春新碱、环磷酰胺和多柔比星(DM-R-EPOCH)已被证明具有高度有效性和安全性。在这项对101例患有B细胞PTLD的成年移植受者的单机构回顾性研究中,65例接受DM-R-EPOCH治疗,8例接受R-CHOP治疗,17例接受R单药治疗。DM-R-EPOCH组的无进展生存期和总生存期的中位数分别为4.4年和6.4年,R-CHOP组分别为1年和1.1年。DM-R-EPOCH组的中性粒细胞减少率和感染率分别为70%和77%,R-CHOP组均为88%。接受DM-R-EPOCH和R-CHOP治疗的患者的治疗相关死亡率分别为4.7%和25%。DM-R-EPOCH的中位疗程数为6个,73%至89%的患者接受的环磷酰胺、依托泊苷和多柔比星的相对剂量强度≥80%。由于PTLD胃肠道受累导致频繁漏用,56%的患者长春新碱的相对剂量强度<80%。总体而言这些数据表明,DM-R-EPOCH不会导致B细胞PTLD患者出现过度毒性,并支持进一步进行前瞻性临床研究的必要性。

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