Long-Term Remission of Acquired von-Willebrand's Disease and Platelet Dysfunction after High-Dose Melphalan in a Patient with Multiple Myeloma

Abstract

Background: Autologous stem cell transplantation is considered a standard of care treatment in eligible patients with multiple myeloma, but puts the patient at high risk for infections and bleeding complications. Acquired von-Willebrand's disease (AVWD) and acquired platelet dysfunction are rare bleeding disorders that are associated with lymphoproliferative disorders such as multiple myeloma. Patients with acquired bleeding disorders who are planned for ASCT to treat the underlying condition are considered at highest risk for bleeding complications, and optimal treatment strategies are not known.
 Materials and Methods: We summarized the diagnostic and therapeutic approach to a patient affected by AVWD and acquired platelet disorder related to multiple myeloma. The patient who was planned for ASCT presented with moderate to severe bleeding symptoms.
 Results: Acute bleeding episodes were successfully controlled and prevented during induction and consolidation therapy with immunoglobulins, whereas replacement of plasma-derived VW factor showed no clinical improvement. High-dose melphalan-based consolidation therapy supported with autologous stem-cell transplantation led to an immediate and sustainable rise of von-Willebrand antigen and activity and a subsequent normalization of platelet aggregation activity. After a follow-up of 40 weeks, the patient maintained normalized VW levels and platelet aggregation capacity. There were no further signs or symptoms of bleeding.
 Conclusion: This case report highlights the necessity for combined supportive and causal treatment in patients with AVWD and paraproteinemic PD. High-dose melphalan with autologous stem cell support may function as a treatment option in patients with myeloma-related AVWD.

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

“…Eight patients benefited from autologous HSCT in PRD, including two patients who underwent two autologous HSCTs 25–27,30,31,33,34 . No severe bleeding was reported.…”

“…Notably, bortezomib steroid‐based regimens were used nine times with an AWS‐ORR of 66.7% (6/9), 19,22,23,25–27,29,30 including associations with thalidomide, 27 melphalan, 25 cyclophosphamide 26,27 and lenalidomide 30 . For ASCT, nine lines of treatment included autologous haematopoietic stem cell transplantation (HSCT) with an AWS‐ORR of 88.9% 25–27,30,31,33,34 . Autologous HSCT was performed immediately 33,34 or was preceded by induction therapy.…”

“…The median and mean times to normalise VWF levels in PRD were 6 and 8.1 months (1–20 months), respectively 17,22,23,25,26,28,36 . Notably, several cases described an improvement of bleeding syndrome prior to the biological improvement of AWS 25,31 .…”

“…22,23,[25][26][27][28][29][30][31]33,34,38 The median and mean times to normalise VWF levels in PRD were 6 and 8.1 months (1-20 months), respectively. 17,22,23,25,26,28,36 Notably, several cases described an improvement of bleeding syndrome prior to the biological improvement of AWS. 25,31 The overall response for AWS was several months to up to two years after the initial improvement of VWF levels and/or clinical bleeding.…”

“…Responses in PRD (PRD-R) were rarely provided, but when the drug used to treat AWS-PRD was an anti-myeloma drug, the AWS-ORR matched the PRD-R for 20/21 lines of treatment (95.2%). 22,23,[25][26][27][28][29][30][31]33,34,38 The median and mean times to normalise VWF levels in PRD were 6 and 8.1 months (1-20 months), respectively. 17,22,23,25,26,28,36 Notably, several cases described an improvement of bleeding syndrome prior to the biological improvement of AWS.…”