Skip to main content
Log in

Features of extramedullary myeloma relapse: high proliferation, minimal marrow involvement, adverse cytogenetics: a retrospective single-center study of 24 cases

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Extramedullary (e) relapse in multiple myeloma (MM) has an adverse prognosis, but knowledge concerning biological features and preferred treatment is scarce. We screened the myeloma registry of our institution for eMM relapses and identified 24 cases among 357 patients (pts). Only 8% of eMM relapses occurred after initial therapy, but 54% occurred after third-line or subsequent therapy. Baseline molecular cytogenetics revealed high-risk features in 10 of 19 evaluable patients. Most frequently, eMM presented as soft tissue (67%) and organ involvement (25%) or malignant effusion (12.5%). Incidence of leptomeningeal/CNS involvement was 21%. At eMM relapse, bone marrow infiltration was absent in 46% and low in 21%. Ten eMM biopsies were available showing increased proliferation, i.e., Ki-67 of 67% (range, 30–90%) of all cancer cells. Pts received radiation therapy, dose-intense chemotherapy, novel agents, and allogeneic SCT resulting in an overall response rate of 54%. Median progression-free survival was 2 (95% CI 0.08–3.92) and median overall survival 7 months (95% CI 3.56–10.43), respectively, with only three patients being alive at 12 months from diagnosis. EMM relapse may present at any anatomical site with frequent CNS involvement. Biological features include increased proliferation and low rate of marrow involvement. Prognosis remains poor despite intensive treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Varettoni M, Corso A, Pica G, Mangiacavalli S, Pascutto C, Lazzarino M (2010) Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients. Ann Oncol 21(2):325–330. doi:https://doi.org/10.1093/annonc/mdp329

    Article  CAS  PubMed  Google Scholar 

  2. Alegre A, Granda A, Martinez-Chamorro C, Diaz-Mediavilla J, Martinez R, Garcia-Larana J, Lahuerta JJ, Sureda A, Blade J, de la Rubia J, Fernandez-Ranada JM, San Miguel J (2002) Different patterns of relapse after autologous peripheral blood stem cell transplantation in multiple myeloma: clinical results of 280 cases from the Spanish Registry. Haematologica 87(6):609–614

    PubMed  Google Scholar 

  3. Blade J, Kyle RA, Greipp PR (1996) Presenting features and prognosis in 72 patients with multiple myeloma who were younger than 40 years. Br J Haematol 93(2):345–351

    Article  CAS  PubMed  Google Scholar 

  4. Perez-Simon JA, Sureda A, Fernandez-Aviles F, Sampol A, Cabrera JR, Caballero D, Martino R, Petit J, Tomas JF, Moraleda JM, Alegre A, Canizo C, Brunet S, Rosinol L, Lahuerta J, Diez-Martin JL, Leon A, Garcia A, Vazquez L, Sierra J, San Miguel JF (2006) Reduced-intensity conditioning allogeneic transplantation is associated with a high incidence of extramedullary relapses in multiple myeloma patients. Leukemia 20(3):542–545. doi:https://doi.org/10.1038/sj.leu.2404085

    Article  CAS  PubMed  Google Scholar 

  5. Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC (2009) Multiple myeloma. Lancet 374(9686):324–339. doi:https://doi.org/10.1016/S0140-6736(09)60221-X

    Article  PubMed  Google Scholar 

  6. Drexler HG, Matsuo Y (2000) Malignant hematopoietic cell lines: in vitro models for the study of multiple myeloma and plasma cell leukemia. Leuk Res 24(8):681–703

    Article  CAS  PubMed  Google Scholar 

  7. Bink K, Haralambieva E, Kremer M, Ott G, Beham-Schmid C, de Leval L, Peh SC, Laeng HR, Jutting U, Hutzler P, Quintanilla-Martinez L, Fend F (2008) Primary extramedullary plasmacytoma: similarities with and differences from multiple myeloma revealed by interphase cytogenetics. Haematologica 93(4):623–626. doi:https://doi.org/10.3324/haematol.12005

    Article  PubMed  Google Scholar 

  8. Lopez-Anglada L, Gutierrez NC, Garcia JL, Mateos MV, Flores T, San Miguel JF (2010) P53 deletion may drive the clinical evolution and treatment response in multiple myeloma. Eur J Haematol 84(4):359–361. doi:https://doi.org/10.1111/j.1600-0609.2009.01399.x

    Article  PubMed  Google Scholar 

  9. Sheth N, Yeung J, Chang H (2009) p53 nuclear accumulation is associated with extramedullary progression of multiple myeloma. Leuk Res 33(10):1357–1360. doi:https://doi.org/10.1016/j.leukres.2009.01.010

    Article  CAS  PubMed  Google Scholar 

  10. Dahl IM, Rasmussen T, Kauric G, Husebekk A (2002) Differential expression of CD56 and CD44 in the evolution of extramedullary myeloma. Br J Haematol 116(2):273–277

    Article  CAS  PubMed  Google Scholar 

  11. Chang H, Bartlett ES, Patterson B, Chen CI, Yi QL (2005) The absence of CD56 on malignant plasma cells in the cerebrospinal fluid is the hallmark of multiple myeloma involving central nervous system. Br J Haematol 129(4):539–541. doi:https://doi.org/10.1111/j.1365-2141.2005.05493.x

    Article  PubMed  Google Scholar 

  12. Minnema MC, van de Donk NW, Zweegman S, Hegenbart U, Schonland S, Raymakers R, Zijlmans JM, Kersten MJ, Bos GM, Lokhorst HM (2008) Extramedullary relapses after allogeneic non-myeloablative stem cell transplantation in multiple myeloma patients do not negatively affect treatment outcome. Bone Marrow Transplant 41(9):779–784. doi:https://doi.org/10.1038/sj.bmt.1705982

    Article  CAS  PubMed  Google Scholar 

  13. Kapoor P, Rajkumar SV (2011) Update on risk stratification and treatment of newly diagnosed multiple myeloma. Int J Hematol 94:310–320

    Article  CAS  PubMed  Google Scholar 

  14. Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, Leyvraz S, Michallet M, Yakoub-Agha I, Garderet L, Marit G, Michaux L, Voillat L, Renaud M, Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dorvaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C (2007) Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood 109(8):3489–3495

    Article  CAS  PubMed  Google Scholar 

  15. Damaj G, Mohty M, Vey N, Dincan E, Bouabdallah R, Faucher C, Stoppa AM, Gastaut JA (2004) Features of extramedullary and extraosseous multiple myeloma: a report of 19 patients from a single center. Eur J Haematol 73(6):402–406. doi:https://doi.org/10.1111/j.1600-0609.2004.00331.x

    Article  CAS  PubMed  Google Scholar 

  16. Cerny J, Fadare O, Hutchinson L, Wang SA (2008) Clinicopathological features of extramedullary recurrence/relapse of multiple myeloma. Eur J Haematol 81(1):65–69. doi:https://doi.org/10.1111/j.1600-0609.2008.01087.x

    Article  PubMed  Google Scholar 

  17. Terpos E, Rezvani K, Basu S, Milne AE, Rose PE, Scott GL, Rahemtulla A, Samson D, Apperley JF (2005) Plasmacytoma relapses in the absence of systemic progression post-high-dose therapy for multiple myeloma. Eur J Haematol 75(5):376–383. doi:https://doi.org/10.1111/j.1600-0609.2005.00531.x

    Article  PubMed  Google Scholar 

  18. Petersen SL, Wagner A, Gimsing P (1999) Cerebral and meningeal multiple myeloma after autologous stem cell transplantation. A case report and review of the literature. Am J Hematol 62(4):228–233

    Article  CAS  PubMed  Google Scholar 

  19. Fassas AB, Muwalla F, Berryman T, Benramdane R, Joseph L, Anaissie E, Sethi R, Desikan R, Siegel D, Badros A, Toor A, Zangari M, Morris C, Angtuaco E, Mathew S, Wilson C, Hough A, Harik S, Barlogie B, Tricot G (2002) Myeloma of the central nervous system: association with high-risk chromosomal abnormalities, plasmablastic morphology and extramedullary manifestations. Br J Haematol 117(1):103–108

    Article  PubMed  Google Scholar 

  20. Xu JL, Lai R, Kinoshita T, Nakashima N, Nagasaka T (2002) Proliferation, apoptosis, and intratumoral vascularity in multiple myeloma: correlation with the clinical stage and cytological grade. J Clin Pathol 55(7):530–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kremer M, Ott G, Nathrath M, Specht K, Stecker K, Alexiou C, Quintanilla-Martinez L, Fend F (2005) Primary extramedullary plasmacytoma and multiple myeloma: phenotypic differences revealed by immunohistochemical analysis. J Pathol 205(1):92–101. doi:https://doi.org/10.1002/path.1680

    Article  CAS  PubMed  Google Scholar 

  22. Waterhouse DF, Moloney GA, Gargoum FS, Hayden PS, O'Gorman T (2009) Extramedullary relapse of IgA-lambda myeloma after recent bortezomib therapy: a case report. Cases J 2:7456. doi:https://doi.org/10.4076/1757-1626-2-7456

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rosinol L, Cibeira MT, Blade J, Esteve J, Aymerich M, Rozman M, Segarra M, Cid MC, Filella X, Montserrat E (2004) Extramedullary multiple myeloma escapes the effect of thalidomide. Haematologica 89(7):832–836

    CAS  PubMed  Google Scholar 

  24. Katodritou E, Gastari V, Verrou E, Hadjiaggelidou C, Varthaliti M, Georgiadou S, Laschos K, Xirou P, Yiannaki E, Constantinou N, Markala D, Zervas K (2009) Extramedullary (EMP) relapse in unusual locations in multiple myeloma: is there an association with precedent thalidomide administration and a correlation of special biological features with treatment and outcome? Leuk Res 33(8):1137–1140. doi:https://doi.org/10.1016/j.leukres.2009.01.036

    Article  CAS  PubMed  Google Scholar 

  25. Balleari E, Ghio R, Falcone A, Musto P (2004) Possible multiple myeloma dedifferentiation following thalidomide therapy: a report of four cases. Leuk Lymphoma 45(4):735–738

    Article  PubMed  Google Scholar 

  26. Nakazato T, Suzuki K, Mihara A, Sanada Y, Kakimoto T (2009) Refractory plasmablastic type myeloma with multiple extramedullary plasmacytomas and massive myelomatous effusion: remarkable response with a combination of thalidomide and dexamethasone. Intern Med 48(20):1827–1832

    Article  PubMed  Google Scholar 

  27. Rosinol L, Cibeira MT, Uriburu C, Yantorno S, Salamero O, Blade J, Montserrat E (2006) Bortezomib: an effective agent in extramedullary disease in multiple myeloma. Eur J Haematol 76(5):405–408. doi:https://doi.org/10.1111/j.0902-4441.2005.t01-1-EJH2462.x

    Article  CAS  Google Scholar 

  28. Calvo-Villas JM, Alegre A (2009) Efficacy of lenalidomide-based regimens in multiple myeloma complicated by extramedullary plasmacytomas at relapse or progression (Abstract 4952). Paper presented at the ASH Annual Meeting Abstracts

  29. Pulini S, Natale A, Fioritoni G (2009) Extramedullary relapses after stem cell transplantation in multiple myeloma. Paper presented at the ASH Annual Meeting Abstracts

  30. Laubach JP, Mahindra A, Mitsiades CS, Schlossman RL, Munshi NC, Ghobrial IM, Carreau N, Hideshima T, Anderson KC, Richardson PG (2009) The use of novel agents in the treatment of relapsed and refractory multiple myeloma. Leukemia 23(12):2222–2232. doi:https://doi.org/10.1038/leu.2009.179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Engelhardt M, Kleber M, Frydrychowicz A, Pache G, Schmitt-Graff A, Wasch R, Durie BG (2009) Superiority of magnetic resonance imaging over conventional radiographs in multiple myeloma. Anticancer Res 29(11):4745–4750

    PubMed  Google Scholar 

  32. Shortt CP, Gleeson TG, Breen KA, McHugh J, O'Connell MJ, O'Gorman PJ, Eustace SJ (2009) Whole-body MRI versus PET in assessment of multiple myeloma disease activity. AJR Am J Roentgenol 192(4):980–986. doi:https://doi.org/10.2214/AJR.08.1633

    Article  PubMed  Google Scholar 

  33. Chen Z, Issa B, Huang S, Aston E, Xu J, Yu M, Brothman AR, Glenn M (2005) A practical approach to the detection of prognostically significant genomic aberrations in multiple myeloma. J Mol Diagn 7(5):560–565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chim CS, Hwang YY, Pang C, Shek TW (2009) Restoration of chemosensitivity by bortezomib: implications for refractory myeloma. Nat Rev Clin Oncol 6(4):237–240. doi:https://doi.org/10.1038/nrclinonc.2009.15

    Article  CAS  PubMed  Google Scholar 

  35. Zeiser R, Deschler B, Bertz H, Finke J, Engelhardt M (2004) Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome. Bone Marrow Transplant 34(12):1057–1065. doi:https://doi.org/10.1038/sj.bmt.1704713

    Article  CAS  PubMed  Google Scholar 

  36. Creach KM, Foote RL, Neben-Wittich MA, Kyle RA (2009) Radiotherapy for extramedullary plasmacytoma of the head and neck. Int J Radiat Oncol Biol Phys 73(3):789–794. doi:https://doi.org/10.1016/j.ijrobp.2008.04.077

    Article  PubMed  Google Scholar 

  37. Yaneva MP, Goranova-Marinova V, Goranov S (2006) Palliative radiotherapy in patients with multiple myeloma. J BUON 11(1):43–48

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Interdisciplinary Center for Clinical Research (IZKF) Wuerzburg, Germany (grant to LR).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Leo Rasche.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rasche, L., Bernard, C., Topp, M.S. et al. Features of extramedullary myeloma relapse: high proliferation, minimal marrow involvement, adverse cytogenetics: a retrospective single-center study of 24 cases. Ann Hematol 91, 1031–1037 (2012). https://doi.org/10.1007/s00277-012-1414-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-012-1414-5

Keywords

Navigation