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Use of propylene glycol-free melphalan conditioning in light-chain amyloidosis patients undergoing autologous hematopoietic cell transplantation is well tolerated and effective

Bone Marrow Transplantation volume 53, pages 1210–1213 (2018)Cite this article

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To the Editor: Light-chain amyloidosis (AL) is a malignant plasma cell disorder, characterized by misfolded fibrillar protein deposition in vitals organs of the body, leading to organ failure and eventually death [1]. Treatment is directed at eradicating the underlying plasma cell clone using systemic chemotherapy [2]. Autologous hematopoietic cell transplantation (auto-HCT) has been a preferred approach in transplant-eligible patients to improve long-term outcomes [3]. High-dose melphalan conditioning is the standard of care for auto-HCT in patients with plasma cell disorders [4]. The lyophilized melphalan formulation has inadequate solubility and stability after reconstitution, and propylene glycol (PG), which is used as a co-solvent to improve solubility and chemical stability of lyophilized melphalan, is associated with cardiac, neurologic, metabolic, and renal toxicities [5, 6]. A novel PG-free melphalan preparation, Evomela® (PG-free melphalan), uses captisol as a solubilizing agent and thus may be less toxic than PG melphalan formulations. In a phase IIb study of multiple myeloma (MM) patients undergoing auto-HCT, PG-free melphalan showed an acceptable safety profile and comparable efficacy [7]. Consequently, PG-free melphalan was granted FDA approval for use as a conditioning regimen in patients undergoing auto-HCT. Since AL patients have increased peri-transplant complications, we sought to determine the safety and efficacy of PG-free melphalan conditioning in AL patients undergoing auto-HCT compared to PG melphalan.

We switched to PG-free melphalan for auto-HCT conditioning on 15 November 2016. Herein, we compare early post-transplant outcomes of AL patients in the year before and after the change. We retrospectively analyzed AL patients who underwent auto-HCT from 31 October 2015 to 31 October 2017 at our institution (N = 18), nine each in PG melphalan and PG-free melphalan group. AL staging was determined using the 2012 revised staging system [8]. Hematologic response was defined according to the 2012-updated AL response criteria [9]. Chart review was conducted to identify events in the first 100 days following auto-HCT, including arrhythmias, cardiac and/or renal failure, mucositis, engraftment syndrome, days in hospital, rehospitalization, and transfer to intensive care unit (ICU). We also reviewed charts for need of platelet and pack red blood cell (PRBC) transfusion post auto-HCT in PG melphalan and PG-free melphalan group. The threshold for PRBC transfusion was hemoglobin <7 g/dl and for platelet transfusion was <10,000/mm3 during this entire period. Incidence and severity of chemotherapy-induced mucositis was determined based on documentation of oral mucositis in the charts and use of opioid medications for oral, throat, or abdominal pain. We also took into account the use of intravenous dexamethasone, intubation to protect airway, and ICU transfer due to suspected oropharyngeal mucositis. Categorical variables between groups were compared using χ2 test. Continuous variables were compared by non-parametric t test using analysis of variance.

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References

  1. Skinner M. AL amyloidosis: the last 30 years. Amyloid. 2000;7:13–4.

    Article  CAS  Google Scholar 

  2. Merlini G, Seldin DC, Gertz MA. Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol. 2011;29:1924–33.

    Article  Google Scholar 

  3. D’Souza A, Dispenzieri A, Wirk B, Zhang MJ, Huang J, Gertz MA. et al. Improved outcomes after autologous hematopoietic cell transplantation for light chain amyloidosis: a Center for International Blood and Marrow Transplant Research study. J Clin Oncol. 2015;33:3741–9.

    Article  Google Scholar 

  4. Cibeira MT, Sanchorawala V, Seldin DC, Quillen K, Berk JL, Dember LM. et al. Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients. Blood. 2011;118:4346–52.

    Article  CAS  Google Scholar 

  5. Barnes BJ, Gerst C, Smith JR, Terrell AR, Mullins ME. Osmol gap as a surrogate marker for serum propylene glycol concentrations in patients receiving lorazepam for sedation. Pharmacotherapy. 2006;26:23–33.

    Article  CAS  Google Scholar 

  6. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20:217–9.

    Article  Google Scholar 

  7. Hari P, Aljitawi OS, Arce-Lara C, Nath R, Callander N, Bhat G. et al. A phase IIb, multicenter, open-label, safety, and efficacy study of high-dose, propylene glycol-free melphalan hydrochloride for injection (EVOMELA) for myeloablative conditioning in multiple myeloma patients undergoing autologous transplantation. Biol Blood Marrow Transplant. 2015;21:2100–5.

    Article  CAS  Google Scholar 

  8. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C. et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30:989–95.

    Article  CAS  Google Scholar 

  9. Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN. et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012;30:4541–9.

    Article  CAS  Google Scholar 

  10. Cashen AF, Fletcher T, Ceriotti C, Gao F, Ghobadi A, Vij R. et al. Phase II study of propylene glycol-free melphalan combined with carmustine, etoposide, and cytarabine for myeloablative conditioning in lymphoma patients undergoing autologous stem cell transplantation. Biol Blood Marrow Transplant. 2016;22:2155–8.

    Article  CAS  Google Scholar 

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Acknowledgements

This publication is funded in part by the Research and Education Program Fund, a component of the Advancing a Healthier Wisconsin endowment at the Medical College of Wisconsin and by KL2TR001438 from the Clinical and Translational Science Award program of the National Center for Advancing Translational Sciences (A.D.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Author contributions

T.B. and A.D. designed the research, analyzed the data, interpreted the results, and wrote the manuscript; P.H., S.C., B.D., W.R.D., T.S.F., M.H., M.P., W.S., N.N.S., and B.E.S. assisted in interpretation and manuscript preparation; all authors approved the final draft of the manuscript.

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  1. Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    Talha Badar, Parameswaran Hari, Saurabh Chhabra, Binod Dhakal, William R. Drobyski, Timothy S. Fenske, Mehdi Hamadani, Marcelo Pasquini, Wael Saber, Nirav N. Shah, Bronwen E. Shaw & Anita D’Souza

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Correspondence to Anita D’Souza.

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Badar, T., Hari, P., Chhabra, S. et al. Use of propylene glycol-free melphalan conditioning in light-chain amyloidosis patients undergoing autologous hematopoietic cell transplantation is well tolerated and effective. Bone Marrow Transplant 53, 1210–1213 (2018). https://doi.org/10.1038/s41409-018-0178-5

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