Service d'Onco-Hématologie, Centre Hospitalier des Pays de Morlaix, Morlaix, France.
Service d'Hématologie Clinique, Institut de Cancéro-Hématologie, CHRU de Brest, Brest, France.
Haemophilia. 2022 Nov;28(6):938-949. doi: 10.1111/hae.14648. Epub 2022 Aug 25.
Acquired von Willebrand syndrome (AWS) is a rare and potentially life-threatening bleeding disorder. AWS is primarily associated with lymphocyte-related disorders (AWS-LRD), such as lymphoma and IgM monoclonal gammopathy of undetermined significance (MGUS), and plasmocyte-related disorders (AWS-PRD), such as non-IgM MGUS and myeloma. Symptomatic treatments are important to control and prevent bleeding, but AWS-LRD and AWS-PRD can only be cured by targeting the responsible clonal cell. No reviews exist on this specific subgroup of AWS.
We performed a literature review to help manage these rare cases.
Thirty-two AWS-PRD and 43 AWS-LRD cases with data on malignancy treatment were reported in 56 articles from the Medline database.
LRDs were exclusively indolent and primarily associated with IgM monoclonal compounds. LRDs and PRDs may be treated because of severe bleeding symptoms, but severe VWF deficiency did not necessarily correlate with severe bleeding. Immunosuppressive drugs in AWS-PRD, including rituximab, provided an overall response rate of AWS (AWS-ORR) of 30% (3/10), including short responses. Anti-myeloma drugs provided an AWS-ORR of 71.4% (20/28), with long-lasting remissions. Bortezomib was the most commonly used drug and provided an AWS-ORR of 66.7% (6/9), including therapeutic associations with other anti-myeloma drugs. Autologous and allogeneic stem cell transplantation was performed in eight and two patients, respectively, and some details on the management of AWS during these procedures were provided. Rituximab in AWS-LRD provided an AWS-ORR of 60% (3/5), and a chemotherapy + rituximab regimen increased the AWS-ORR to above 50%. Bleeding syndrome in AWS-PRD and AWS-LRD generally improved prior to AWS biological improvement.
Long term remission of AWS due to lymphoid neoplasms is attainable by treating the underlying clonal cell. Some data and recommendations are provided to help answer difficult questions, including treatment timing, choice of drug, and the timing of evaluations and treatment changes.
获得性血管性血友病（AWS）是一种罕见且潜在危及生命的出血性疾病。AWS 主要与淋巴细胞相关疾病（AWS-LRD）相关，如淋巴瘤和免疫球蛋白 M 单克隆丙种球蛋白血症（MGUS），以及浆细胞相关疾病（AWS-PRD），如非免疫球蛋白 M MGUS 和骨髓瘤。对症治疗对于控制和预防出血很重要，但 AWS-LRD 和 AWS-PRD 只能通过靶向负责的克隆细胞来治愈。目前尚无关于 AWS 这一特定亚组的综述。
我们进行了文献回顾，以帮助管理这些罕见病例。
从 Medline 数据库的 56 篇文章中报告了 32 例 AWS-PRD 和 43 例 AWS-LRD 病例，这些病例均有恶性肿瘤治疗的数据。
LRD 均为惰性，主要与免疫球蛋白 M 单克隆化合物相关。LRD 和 PRD 可能因严重出血症状而接受治疗，但严重的 VWF 缺乏并不一定与严重出血相关。AWS-PRD 中的免疫抑制药物，包括利妥昔单抗，总体反应率为 AWS（AWS-ORR）为 30%（3/10），包括短暂反应。抗骨髓瘤药物的 AWS-ORR 为 71.4%（20/28），缓解持久。硼替佐米是最常用的药物，AWS-ORR 为 66.7%（6/9），包括与其他抗骨髓瘤药物的治疗联合。分别对 8 例和 2 例患者进行了自体和同种异体干细胞移植，并提供了一些关于这些治疗过程中 AWS 管理的细节。LRD 中的利妥昔单抗 AWS-ORR 为 60%（3/5），化疗+利妥昔单抗方案可将 AWS-ORR 提高至 50%以上。AWS-PRD 和 AWS-LRD 的出血综合征在 AWS 生物学改善之前通常会有所改善。
通过治疗潜在的克隆细胞，可实现淋巴肿瘤相关的 AWS 长期缓解。提供了一些数据和建议，以帮助回答一些困难的问题，包括治疗时机、药物选择以及评估和治疗改变的时机。
