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High-dose melphalan and stem cell transplantation in systemic AL amyloidosis in the era of novel anti-plasma cell therapy: a comprehensive review

Bone Marrow Transplantation (2018) | Download Citation

Abstract

The application of high-dose melphalan and autologous stem cell transplant (SCT) to systemic AL amyloidosis (AL) has evolved over the past two decades and remains an important component of therapy for patients with AL. The era of novel agents created the opportunity to provide well -tolerated induction and post-SCT consolidation to AL patients eligible for SCT and the current availability of new monoclonal antibody therapies will likely provide additional opportunities to enhance the outcomes with SCT. In this review, we touch on the history of SCT for AL and examine the data on eligibility, mobilization, induction, risk-adapted melphalan dosing, engraftment, consolidation and maintenance, and long-term outcomes with SCT. We note that induction therapy may deprive some patients of the opportunity to proceed to SCT but is likely needed if the marrow plasmacytosis is > 10%, that risk-adapted melphalan dosing continues to be relevant, and that post-SCT consolidation improves the complete response rate as well as long-term overall survival. The importance of baseline cytogenetics is also highlighted, particularly for patients whose clonal plasma cells are ≤ 10% but harbor the t(11;14), because they may have improved survival with SCT.

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Acknowledgements

We thank the Division of Hematology-Oncology and Departments of Medicine and Pathology and Laboratory Medicine at Tufts for their continued support, and also acknowledge the support by the Amyloidosis and Myeloma Research Fund at Tufts, the Cam Neely and John Davis Myeloma Research Fund, the John C Davis Program for Myeloma and Amyloid at Tufts, the Sidewater Family Fund, the Lavonne Horowitz Trust, the Werner and Elaine Dannheiser Fund for Research on the Biology of Aging of the Lymphoma Foundation, David and Barbara Levine (in memoriam), and the Demarest Lloyd Jr Foundation.

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  1. The Division of Hematology-Oncology, Department of Medicine, Tufts Medical Center, Boston, MA, USA

    • Cindy Varga
    •  & Raymond L. Comenzo
  2. The John Conant Davis Myeloma and Amyloid Program, Tufts Medical Center, Boston, MA, USA

    • Cindy Varga
    •  & Raymond L. Comenzo

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The authors declare that they have no conflict of interest.

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Correspondence to Cindy Varga.

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https://doi.org/10.1038/s41409-018-0284-4