Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

A model for predicting day-100 stem cell transplant-related mortality in AL amyloidosis

Bone Marrow Transplantation volume 60, pages 595–602 (2025)Cite this article

Subjects

Abstract

Autologous stem cell Transplant (ASCT)-related mortality (TRM) in AL amyloidosis remains elevated. AL amyloidosis patients (n = 1718) from 9 centers, transplanted 2003–2020 were included. Pre-ASCT variables of interest were assessed for association with day-100 all-cause mortality. A random forest (RF) classifier with 10-fold cross-validation assisted in variable selection. The final model was fitted using logistic regression. The median age at ASCT was 58 years. Day-100 TRM occurred in 75 patients (4.4%) with the predominant causes being shock, high-grade arrhythmia, and organ failure. Ten factors were associated with day-100 TRM on univariate analysis. RF classifier using these variables generated a model with an area under the curve (AUC) of 0.72 ± 0.12. To refine the model selection using importance hierarchy function, a 4-variable model [NT-proBNP/BNP, serum albumin, ECOG performance status (PS), and systolic blood pressure] was built with an AUC of 0.70 ± 0.12. Based on logistic regression coefficients, ECOG PS 2/3 was assigned two points while other adverse predictors 1-point each. The model score range was 0–5, with a day-100 TRM of 0.46%, 3.2%, 5.8%, and 14.5% for 0, 1, 2, and ≥3 points, respectively. This model to predict day-100 TRM in AL amyloidosis allows better-informed decision-making in this heterogeneous disease.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Day-100 TRM weekly distribution.
Fig. 2: SHAP summary plot.
Fig. 3: ROC-AUC of the model.

Similar content being viewed by others

Data availability

The dataset of this study is not publicly available due to the proprietary nature of the electronic health records and maintaining patient anonymity mandated by the institutional review boards.

References

  1. Sanchorawala V, Boccadoro M, Gertz M, Hegenbart U, Kastritis E, Landau H, et al. Guidelines for high dose chemotherapy and stem cell transplantation for systemic AL amyloidosis: EHA-ISA working group guidelines. Amyloid. 2022;29:1–7. https://doi.org/10.1080/13506129.2021.2002841.

    Article  CAS  PubMed  Google Scholar 

  2. 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. https://doi.org/10.1182/blood-2011-01-330738.

    Article  CAS  PubMed  PubMed Central  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. https://doi.org/10.1200/JCO.2015.62.4015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gertz MA, Schonland S. Stem cell mobilization and autologous transplant for immunoglobulin light-chain amyloidosis. Hematol Oncol Clin North Am. 2020;34:1133–44. https://doi.org/10.1016/j.hoc.2020.07.007.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gutierrez-Garcia G, Cibeira MT, Rovira M, Fernandez de Larrea C, Tovar N, Rodriguez-Lobato LG, et al. Improving security of autologous hematopoietic stem cell transplant in patients with light-chain amyloidosis. Bone Marrow Transplant. 2019;54:1295–303. https://doi.org/10.1038/s41409-019-0447-y.

    Article  CAS  PubMed  Google Scholar 

  6. Jaccard A, Moreau P, Leblond V, Leleu X, Benboubker L, Hermine O, et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007;357:1083–93. https://doi.org/10.1056/NEJMoa070484.

    Article  CAS  PubMed  Google Scholar 

  7. Sharpley FA, Petrie A, Mahmood S, Sachchithanantham S, Lachmann HJ, Gillmore JD, et al. A 24-year experience of autologous stem cell transplantation for light chain amyloidosis patients in the United Kingdom. Br J Haematol. 2019;187:642–52. https://doi.org/10.1111/bjh.16143.

    Article  CAS  PubMed  Google Scholar 

  8. Skinner M, Sanchorawala V, Seldin DC, Dember LM, Falk RH, Berk JL, et al. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med. 2004;140:85–93. https://doi.org/10.7326/0003-4819-140-2-200401200-00008.

    Article  CAS  PubMed  Google Scholar 

  9. Tandon N, Muchtar E, Sidana S, Dispenzieri A, Lacy MQ, Dingli D, et al. Revisiting conditioning dose in newly diagnosed light chain amyloidosis undergoing frontline autologous stem cell transplant: impact on response and survival. Bone Marrow Transplant. 2017;52:1126–32. https://doi.org/10.1038/bmt.2017.68.

    Article  CAS  PubMed  Google Scholar 

  10. Tsai SB, Seldin DC, Quillen K, Berk JL, Ruberg FL, Meier-Ewert H, et al. High-dose melphalan and stem cell transplantation for patients with AL amyloidosis: trends in treatment-related mortality over the past 17 years at a single referral center. Blood. 2012;120:4445–6. https://doi.org/10.1182/blood-2012-09-457341.

    Article  CAS  PubMed  Google Scholar 

  11. Gertz MA, Lacy MQ, Dispenzieri A, Kumar SK, Dingli D, Leung N, et al. Refinement in patient selection to reduce treatment-related mortality from autologous stem cell transplantation in amyloidosis. Bone Marrow Transplant. 2013;48:557–61. https://doi.org/10.1038/bmt.2012.170.

    Article  CAS  PubMed  Google Scholar 

  12. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK, Dingli D, et al. Autologous stem cell transplant for immunoglobulin light chain amyloidosis: a status report. Leuk Lymphoma. 2010;51:2181–7. https://doi.org/10.3109/10428194.2010.524329.

    Article  PubMed  Google Scholar 

  13. Dingli D, Tan TS, Kumar SK, Buadi FK, Dispenzieri A, Hayman SR, et al. Stem cell transplantation in patients with autonomic neuropathy due to primary (AL) amyloidosis. Neurology. 2010;74:913–8. https://doi.org/10.1212/WNL.0b013e3181d55f4d.

    Article  CAS  PubMed  Google Scholar 

  14. Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385:46–58. https://doi.org/10.1056/NEJMoa2028631.

    Article  CAS  PubMed  Google Scholar 

  15. Kastritis E, Wechalekar AD, Dimopoulos MA, Merlini G, Hawkins PN, Perfetti V, et al. Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. J Clin Oncol. 2010;28:1031–7. https://doi.org/10.1200/JCO.2009.23.8220.

    Article  CAS  PubMed  Google Scholar 

  16. Manwani R, Cohen O, Sharpley F, Mahmood S, Sachchithanantham S, Foard D, et al. A prospective observational study of 915 patients with systemic AL amyloidosis treated with upfront bortezomib. Blood. 2019;134:2271–80. https://doi.org/10.1182/blood.2019000834.

    Article  CAS  PubMed  Google Scholar 

  17. 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. https://doi.org/10.1200/JCO.2011.38.5724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wechalekar AD, Schonland SO, Kastritis E, Gillmore JD, Dimopoulos MA, Lane T, et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood. 2013;121:3420–7. https://doi.org/10.1182/blood-2012-12-473066.

    Article  CAS  PubMed  Google Scholar 

  19. Dispenzieri A, Kyle RA, Gertz MA, Therneau TM, Miller WL, Chandrasekaran K, et al. Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins. Lancet. 2003;361:1787–9. https://doi.org/10.1016/S0140-6736(03)13396-X.

    Article  CAS  PubMed  Google Scholar 

  20. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9. https://doi.org/10.1182/blood-2005-05-2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Leung N, Kumar SK, Glavey SV, Dispenzieri A, Lacy MQ, Buadi FK, et al. The impact of dialysis on the survival of patients with immunoglobulin light chain (AL) amyloidosis undergoing autologous stem cell transplantation. Nephrol Dial Transplant. 2016;31:1284–9. https://doi.org/10.1093/ndt/gfv328.

    Article  CAS  PubMed  Google Scholar 

  22. Rezk T, Lachmann HJ, Fontana M, Naharro AM, Sachchithanantham S, Mahmood S, et al. Cardiorenal AL amyloidosis: risk stratification and outcomes based upon cardiac and renal biomarkers. Br J Haematol. 2019;186:460–70. https://doi.org/10.1111/bjh.15955.

    Article  CAS  PubMed  Google Scholar 

  23. Park MA, Mueller PS, Kyle RA, Larson DR, Plevak MF, Gertz MA. Primary (AL) hepatic amyloidosis: clinical features and natural history in 98 patients. Medicine. 2003;82:291–8. https://doi.org/10.1097/01.md.0000091183.93122.c7.

    Article  PubMed  Google Scholar 

  24. Dispenzieri A, Gertz MA, Kyle RA, Lacy MQ, Burritt MF, Therneau TM, et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol. 2004;22:3751–7. https://doi.org/10.1200/JCO.2004.03.029.

    Article  CAS  PubMed  Google Scholar 

  25. Palladini G, Sachchithanantham S, Milani P, Gillmore J, Foli A, Lachmann H, et al. A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis. Blood. 2015;126:612–5. https://doi.org/10.1182/blood-2015-01-620302.

    Article  CAS  PubMed  Google Scholar 

  26. Muchtar E, Kumar SK, Gertz MA, Grogan M, AbouEzzeddine OF, Jaffe AS, et al. Staging systems use for risk stratification of systemic amyloidosis in the era of high-sensitivity troponin T assay. Blood. 2019;133:763–6. https://doi.org/10.1182/blood-2018-10-875252.

    Article  CAS  PubMed  Google Scholar 

  27. Azur MJ, Stuart EA, Frangakis C, Leaf PJ. Multiple imputation by chained equations: what is it and how does it work? Int J Methods Psychiatr Res. 2011;20:40–49. https://doi.org/10.1002/mpr.329.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Barrett CD, Dobos K, Liedtke M, Tuzovic M, Haddad F, Kobayashi Y, et al. A changing landscape of mortality for systemic light chain amyloidosis. JACC Heart Fail. 2019;7:958–66. https://doi.org/10.1016/j.jchf.2019.07.007.

    Article  PubMed  Google Scholar 

  29. Khwaja J, Ravichandran S, Bomsztyk J, Cohen O, Foard D, Martinez-Naharro A, et al. Limited utility of Mayo 2012 cardiac staging system for risk stratification of patients with advanced cardiac AL amyloidosis—analysis of a uniformly treated cohort of 1,275 patients. Haematologica. 2024;109:1598–602. https://doi.org/10.3324/haematol.2023.284348.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Sidiqi MH, Aljama MA, Buadi FK, Warsame RM, Lacy MQ, Dispenzieri A, et al. Stem cell transplantation for light chain amyloidosis: decreased early mortality over time. J Clin Oncol. 2018;36:1323–9. https://doi.org/10.1200/JCO.2017.76.9554.

    Article  PubMed  Google Scholar 

  31. Ho M, Moscvin M, Low SK, Evans B, Close S, Schlossman R, et al. Risk factors for the development of orthostatic hypotension during autologous stem cell transplant in patients with multiple myeloma. Leuk Lymphoma. 2022;63:2403–12. https://doi.org/10.1080/10428194.2022.2084729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Muchtar E, Lin G, Grogan M. The challenges in chemotherapy and stem cell transplantation for light-chain amyloidosis. Can J Cardiol. 2020;36:384–95. https://doi.org/10.1016/j.cjca.2019.11.032.

    Article  PubMed  Google Scholar 

  33. Biran N, Sehgal P, Sahni G, Doucette J, Chari A. Outcome of patients with multiple myeloma and hypotension during high-dose chemotherapy. Am J Hematol. 2015;90:E125–127. https://doi.org/10.1002/ajh.23991.

    Article  PubMed  Google Scholar 

  34. Hryciw N, Joannidis M, Hiremath S, Callum J, Clark EG. Intravenous albumin for mitigating hypotension and augmenting ultrafiltration during kidney replacement therapy. Clin J Am Soc Nephrol. 2021;16:820–8. https://doi.org/10.2215/CJN.09670620.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lee SY, Meehan RS, Seldin DC, Sloan JM, Quillen K, Shelton A, et al. Effect of severe hypoalbuminemia on toxicity of high-dose melphalan and autologous stem cell transplantation in patients with AL amyloidosis. Bone Marrow Transplant. 2016;51:1318–22. https://doi.org/10.1038/bmt.2016.132.

    Article  CAS  PubMed  Google Scholar 

  36. Levy BI, Schiffrin EL, Mourad JJ, Agostini D, Vicaut E, Safar ME, et al. Impaired tissue perfusion: a pathology common to hypertension, obesity, and diabetes mellitus. Circulation. 2008;118:968–76. https://doi.org/10.1161/CIRCULATIONAHA.107.763730.

    Article  PubMed  Google Scholar 

  37. Sharma PP, Payvar S, Litovsky SH. Histomorphometric analysis of intramyocardial vessels in primary and senile amyloidosis: epicardium versus endocardium. Cardiovasc Pathol. 2008;17:65–71. https://doi.org/10.1016/j.carpath.2007.05.008.

    Article  PubMed  Google Scholar 

  38. Mellgard GS, Bhutani D, Mapara MY, Maurer MS, Radhakrishnan J, Lentzsch S, et al. High-dose melphalan-autologous hematopoietic cell transplantation in systemic AL amyloidosis following daratumumab-based frontline therapy. Bone Marrow Transplant. 2024;59:1181–3. https://doi.org/10.1038/s41409-024-02301-7.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the Mayo Clinic Transplant Center Scholarly Award.

Author information

Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    Eli Muchtar, Angela Dispenzieri, Francis Buadi & Morie Gertz

  2. Section of Hematology and Oncology, Amyloidosis Center, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, MA, USA

    Vaishali Sanchorawala & Hamza Hassan

  3. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA

    Raphael Mwangi & Matthew Maurer

  4. Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Hans C. Lee

  5. Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Muzaffar Qazilbash

  6. Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Andrew Kin & Jeffrey Zonder

  7. Stanford University School of Medicine, Stanford, CA, USA

    Sally Arai & Michelle M. Chin

  8. University of Central Florida College of Medicine, Orlando, FL, USA

    Michelle M. Chin

  9. Division of Hematology/Oncology, Columbia University Medical Center, New York, NY, USA

    Rajshekhar Chakraborty & Suzanne Lentzsch

  10. Hematology Institute, Chaim Sheba Medical Center, Tel Hashomer, and Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel

    Hila Magen & Eden Shkury

  11. Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Caitlin Sarubbi & Heather Landau

  12. Medical Department V, Amyloidosis Center, University of Heidelberg, Heidelberg, Germany

    Stefan Schönland & Ute Hegenbart

Authors
  1. Eli Muchtar
    View author publications

    Search author on:PubMed Google Scholar

  2. Angela Dispenzieri
    View author publications

    Search author on:PubMed Google Scholar

  3. Vaishali Sanchorawala
    View author publications

    Search author on:PubMed Google Scholar

  4. Hamza Hassan
    View author publications

    Search author on:PubMed Google Scholar

  5. Raphael Mwangi
    View author publications

    Search author on:PubMed Google Scholar

  6. Matthew Maurer
    View author publications

    Search author on:PubMed Google Scholar

  7. Francis Buadi
    View author publications

    Search author on:PubMed Google Scholar

  8. Hans C. Lee
    View author publications

    Search author on:PubMed Google Scholar

  9. Muzaffar Qazilbash
    View author publications

    Search author on:PubMed Google Scholar

  10. Andrew Kin
    View author publications

    Search author on:PubMed Google Scholar

  11. Jeffrey Zonder
    View author publications

    Search author on:PubMed Google Scholar

  12. Sally Arai
    View author publications

    Search author on:PubMed Google Scholar

  13. Michelle M. Chin
    View author publications

    Search author on:PubMed Google Scholar

  14. Rajshekhar Chakraborty
    View author publications

    Search author on:PubMed Google Scholar

  15. Suzanne Lentzsch
    View author publications

    Search author on:PubMed Google Scholar

  16. Hila Magen
    View author publications

    Search author on:PubMed Google Scholar

  17. Eden Shkury
    View author publications

    Search author on:PubMed Google Scholar

  18. Caitlin Sarubbi
    View author publications

    Search author on:PubMed Google Scholar

  19. Heather Landau
    View author publications

    Search author on:PubMed Google Scholar

  20. Stefan Schönland
    View author publications

    Search author on:PubMed Google Scholar

  21. Ute Hegenbart
    View author publications

    Search author on:PubMed Google Scholar

  22. Morie Gertz
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Conceptualization: Eli Muchtar, Morie Gertz. Data curation: Eli Muchtar, Angela Dispenzieri, Vaishali Sanchorawala, Hamza Hassan, Francis Buadi, Hans C. Lee, Muzaffar Qazilbash, Andrew Kin, Jeffrey Zonder, Sally Arai, Michelle M. Chin, Rajshekhar Chakraborty, Suzanne Lentzsch, Hila Magen, Eden Shkury, Caitlin Sarubbi, Heather Landau, Stefan Schönland, Ute Hegenbart, Morie Gertz. Formal and statistical analysis: Eli Muchtar, Angela Dispenzieri, Raphael Mwangi, Matthew Maurer, Morie Gertz. Original draft writing: Eli Muchtar, Morie Gertz, Draft editing and critical review: All authors. Approval of final draft: All authors.

Corresponding author

Correspondence to Eli Muchtar.

Ethics declarations

Competing interests

EM received a consultation fee from Protego (a fee paid to the institution). AD received research funding from Celgene, Millennium Pharmaceuticals, Pfizer, and Janssen and received a travel grant from Pfizer. VS received research support from Celgene, Millennium-Takeda, Janssen, Prothena, Sorrento, Karyopharm, Oncopeptide, Caelum, serves as a consultant for Janssen and Pfizer and served on the advisory board for Proclara, Caelum, Abbvie, Janssen, Regeneron, Protego, Pharmatrace, Telix, Prothena. MM received research funding from Roche/Genentech, BMS, and GenMab and provided consultancy/Advisory Board for AstraZeneca and BMS. HCL received research funding from Amgen, Bristol Myers Squibb, Janssen, GlaxoSmithKline, Regeneron, and Takeda Pharmaceuticals and provided consultancy to Abbvie, Bristol Myers Squibb, Janssen, Regeneron, GlaxoSmithKline, Sanofi, Takeda Pharmaceuticals, Allogene Therapeutics, and Pfizer. RC serves as Consultant/Advisory Board for Janssen, Sanofi, Adaptive Biotech and received research funding from Genentech, AbbVie. UH received honoraria from Janssen, Pfizer, Alnylam, Prothena, Astra Zeneca, received financial support for congress participation from Janssen, Prothena, and Pfizer, serves on advisory Boards for Pfizer, Prothena, Janssen, Alexion, Alnylam and received financial sponsoring of Amyloidosis Registry from Janssen. MAG served as a consultant for Millennium Pharmaceuticals and received honoraria from Celgene, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Novartis, GlaxoSmithKline, Prothena, Ionis Pharmaceuticals, and Amgen). The remaining authors declare no competing financial interests.

Ethics approval and consent to participate statement

All methods were performed in accordance with the relevant guidelines and regulations. The study was approved by the IRBs in all participating centers [lead site (Mayo Clinic) IRB number 20-011936]. Informed consent for medical research was obtained from all participants.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Muchtar, E., Dispenzieri, A., Sanchorawala, V. et al. A model for predicting day-100 stem cell transplant-related mortality in AL amyloidosis. Bone Marrow Transplant 60, 595–602 (2025). https://doi.org/10.1038/s41409-025-02535-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41409-025-02535-z

Search

Advanced search

Quick links