Acquired von Willebrand syndrome and lymphoid neoplasms: A review of malignancy management, and propositions of practical recommendations

Abstract

Introduction: 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.

Aim: We performed a literature review to help manage these rare cases.

Method: Thirty-two AWS-PRD and 43 AWS-LRD cases with data on malignancy treatment were reported in 56 articles from the Medline database.

Results: 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.

Conclusion: 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.

Keywords: MGUS; acquired von Willebrand; guideline; lymphoma; lymphoproliferative disease; myeloma.