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Stem cell transplantation in patients with systemic AL amyloidosis referred for transplant after suboptimal responses to bortezomib-based initial therapy

Bone Marrow Transplantation volume 52, pages 936–937 (2017)Cite this article

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Toxic Ig light chains secreted by neoplastic plasma cells, and the fibrillar deposits they form cause light chain (AL) amyloidosis. Current treatments for AL target the neoplastic plasma cells in order to eliminate light chain production, stop and possibly reverse organ damage. Depth of hematologic response is thus a surrogate marker for survival.1 Only 25% of newly diagnosed AL patients have sufficient organ reserve to be considered eligible for stem cell transplantation (SCT). In a recent report, bortezomib-based initial therapy for AL patients ineligible for SCT reduced light chain production and reversed organ damage sufficiently enough to enable 33% to become eligible for SCT.2 As this series indicated, the treatment of AL patients has dramatically improved with bortezomib-based therapy and the rapid deep hematologic responses it effects. Hematologic response rates of 62% have been reported in a large series with 43% of patients achieving very good partial (VGPR) or complete responses (CR).3 Not all centers offer SCT for AL and, given the efficacy of bortezomib-based initial therapy, not all AL patients opt for SCT at diagnosis even if they are eligible.

We report a series of patients (N=12) with biopsy-proven AL amyloidosis who had less than a very good partial response (PR) to bortezomib-based initial therapy (nine had no response (NR) and three PR), and therefore were likely to have inferior overall survival,1 who then underwent SCT with risk-adapted melphalan. The median age was 58 (range, 53–70) and 9 were male. Ten came to us after being treated elsewhere; they did not receive SCT as first-line treatment because of plasma cells >10%, institutional limitations or poor performance status. Two patients diagnosed at our center as eligible for SCT refused our recommendation and chose bortezomib-based therapy instead. Nine patients were treated with bortezomib, cyclophosphamide and dexamethasone, and 3 with bortezomib and dexamethasone, for a median of 4 cycles (2–8). Patients receiving 2 or 3 cycles were switched to SCT because of the risk of organ disease progression due to ineffective therapy as is standard practice.4

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Acknowledgements

SW’s effort was supported in part by the Werner and Elaine Dannheiser Fund for Research on the Biology of Aging of the Lymphoma Foundation and by a Multiple Myeloma Research Foundation fellowship.

Author contributions

SW, MW and RLC collected and analyzed the data and wrote the manuscript. DL, KS and TF collected the data, monitored the patients and wrote the manuscript.

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Authors and Affiliations

  1. Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA, USA

    S W Wong

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

    D Larivee, K A Sprague, T Fogaren & R L Comenzo

  3. Division of Hematology-Oncology, The John C Davis Myeloma and Amyloid Program, Tufts Medical Center, Boston, MA, USA

    M Warner, K A Sprague, T Fogaren & R L Comenzo

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  1. S W Wong
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Correspondence to R L Comenzo.

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Wong, S., Larivee, D., Warner, M. et al. Stem cell transplantation in patients with systemic AL amyloidosis referred for transplant after suboptimal responses to bortezomib-based initial therapy. Bone Marrow Transplant 52, 936–937 (2017). https://doi.org/10.1038/bmt.2017.47

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