Acquired von Willebrand syndrome and lymphoproliferative disorders: A case report

Nicol, Christophe; Raj, Leela; Guillerm, Gaëlle; Couturaud, Francis; Eveillard, Jean‐Richard; Pan‐Petesch, Brigitte

doi:10.1002/ccr3.2770

Cited by 6 publications

(25 citation statements)

References 17 publications

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“…Data are scarce, but the clinical response of AWS generally precedes the first improvement of VWF biology, and sometimes occurs years before the normalisation of VWF biology, but the LRD/PRD may have responded quickly. 25,31,48,51 In our opinion, the absence of biological improvement of AWS in the context of a reduction of haemorrhagic syndrome and PRD/LRD response should not induce a modification of the treatment.…”

Section: Discussionmentioning

confidence: 92%

“…AWS was often the unique reason to initiate malignancy treatment, notably in PRD, which emphasises the difficult choice to treat the underlying disorder because there is no test to firmly establish the link between AWS and LRD or PRD. There is no clear correlation between the clinical and biological severity of AWS, and severe biological AWS may be present for years without clinical impact, which makes treatment initiation of the underlying malignancy at the proper time even more difficult 25 . Strict education on these patients would be important to alert haematologists when new bleeding symptoms appear.…”

Section: Discussionmentioning

confidence: 99%

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

2022

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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.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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

2022

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“…Consequently, lenalidomide is unlikely suited as a treatment in patients with an elevated risk of thromboembolism or a prior history of thromboembolism. In this setting, an alternative combinations of therapies including daratumumab, bortezomib, cyclophosphamide, and dexamethasone may be considered [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Successful use of lenalidomide to treat refractory acquired von Willebrand disease associated with monoclonal gammopathy

et al. 2022

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Acquired von Willebrand syndrome (AVWS) is a rare hematologic disorder characterized by quantitative or qualitative defects of von Willebrand factor (vWF), a protein crucial for normal hemostasis. AVWS has been described in association with several pathologic entities with varied mechanisms. Among these, lymphoproliferative disorders are the most common, with monoclonal gammopathy of undetermined significance (MGUS) being the most frequently reported. AVWS in this setting is commonly associated with the development of bleeding that is clinically challenging to manage due to accelerated clearance of vWF, limiting the utility of many conventional treatment modalities such as DDAVP or vWF/FVIII. We report a case of a 43-year-old male who was sent to our institution for new-onset easy bruising and laboratories concerning for von Willebrand disease (vWD). Further diagnostic workup revealed evidence of an IgG monoclonal gammopathy and findings suggestive of vWF inhibition. Ultimately, he was found to have monoclonal gammopathy of clinical significance (MGCS)-associated AVWS refractory to conventional treatment but responsive to lenalidomide and dexamethasone. This case suggests that lenalidomide may be suitable for patients with AVWS secondary to MGCS.

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“…A number of recently published cases reported encouraging results with clonal directed treatment [ 12 – 14 ]; however, the experience from these cases showed that remissions were less likely to be durable if single drug regimens were used or if the treatment was discontinued prematurely, i.e. before the causative plasma cell clone was sufficiently eradicated.…”

Section: Discussionmentioning

confidence: 99%

“…While in patients with end-organ damage related to MM, immediate treatment is required and recommended according to international guidelines, the approach in avWS patients with MGUS or SMM without end-organ damage or formal treatment indications is less clear [ 11 ]. Several groups reported improvement or even normalization of MG-avWS following antimyeloma treatment [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Successful treatment of acquired von Willebrand syndrome associated with monoclonal gammopathy

Jeryczynski

Agis

Eichinger-Hasenauer

et al. 2022

Wien Klin Wochenschr

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SummaryAcquired von Willebrand syndrome is exceedingly rare and accounts for only 1–3% of von Willebrand disease cases. In this short report, we present our own cases of acquired von Willebrand syndrome associated with monoclonal gammopathy. Both cases went into complete and sustained remission after intensive antimyeloma treatment. The first patient was not deemed fit for autologous stem cell transplantation and was managed with an extensive multidrug combination including daratumumab, carfilzomib, lenalidomide, cyclophosphamide and dexamethasone. After at least VGPR was achieved the coagulation studies rapidly normalized and remained normal after treatment de-escalation to lenalidomide/dexamethasone maintenance. The second patient successfully underwent ASCT after 5 cycles of induction with daratumumab, bortezomib, cyclophosphamide and dexamethasone and has remained in full hematologic and hemostaseologic remission ever since.The two cases highlight the efficacy of aggressive antimyeloma treatment in monoclonal gammopathy-associated acquired von Willebrand syndrome to achieve normalization of coagulation study, providing a possible way to manage these patients.

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Acquired von Willebrand syndrome and lymphoproliferative disorders: A case report

Cited by 6 publications

References 17 publications

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

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

Successful use of lenalidomide to treat refractory acquired von Willebrand disease associated with monoclonal gammopathy

Successful treatment of acquired von Willebrand syndrome associated with monoclonal gammopathy

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