open access

Vol 52, No 5 (2021)
Original research article
Submitted: 2021-09-14
Accepted: 2021-09-14
Get Citation

The prognostic significance of bone marrow histological evaluation in patients with multiple myeloma

Andrzej Szczepaniak1, Macie Kaźmierczak1, Mieczysław Komarnicki1, Anna Przybylowicz-Chalecka1, Violetta Filas2, Michał Michalak3, Lidia Gil1
DOI: 10.5603/AHP.2021.0088
·
Acta Haematol Pol 2021;52(5):493-503.
Affiliations
  1. Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences Poznan, Poland
  2. Department of Tumor Pathology and Prophylaxis, Poznan University of Medical Sciences, Poznan, Poland
  3. Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland

open access

Vol 52, No 5 (2021)
ORIGINAL RESEARCH ARTICLE
Submitted: 2021-09-14
Accepted: 2021-09-14

Abstract

Introduction: Recently, there has been enormous progress in the diagnosis and treatment of multiple myeloma (MM). Despite the importance of flow cytometry and cytogenetic, biomarkers are being sought to assess prognosis and response to treatment. The aim of this study was to determine the significance of histological evaluation and immunohistochemical markers in MM patients.

Material and methods: A retrospective analysis was performed in 90 bone marrow (BM) biopsies collected during the diagnosis period and related to the recognized prognostic factors and response to treatment. The standardized staining methods and monoclonal antibodies were used to detect cluster of differentiation antigens — CD138, CD56, CD20, CD117, cyclin D1, p53, kappa and lambda light chains.

Results: During the follow-up period of 49.6 (2–119.7) months in patients with increased levels of β2-microglobulin, higher International Prognostic Classification stage, with resistance to induction and higher relapse rate after first-line, a clonal lambda plasmocytes infiltration was observed. It also affected the response to induction with immunomodulatory drugs (IMiDs), but not bortezomib. The lowest response rate to IMiDs was noted in patients with CD117-lambda+ and CD56-lambda+ plasma cells. Clonal lambda hyperplasia connected with reduction in overall survival [hazard ratio (HR) 2.4; 95% confidence interval (CI): 0.96–5.92; p =0.047) and progression-free survival (PFS) (HR 4,32, 95% CI: 1.9–9.5; p =0.0002). The presence of plasmocytes with phenotype CD117-lambda+ (HR 3.37; 95% CI: 1.57–7.24; p =0.002) and CD56-lambda+ (HR 3,44; 95% CI: 1,63–7,27; p =0.001) contributed to PFS shortening.

Conclusions: In conclusions, BM biopsy with immunohistochemistry allow the identification of poorly prognostic patients with MM.

Abstract

Introduction: Recently, there has been enormous progress in the diagnosis and treatment of multiple myeloma (MM). Despite the importance of flow cytometry and cytogenetic, biomarkers are being sought to assess prognosis and response to treatment. The aim of this study was to determine the significance of histological evaluation and immunohistochemical markers in MM patients.

Material and methods: A retrospective analysis was performed in 90 bone marrow (BM) biopsies collected during the diagnosis period and related to the recognized prognostic factors and response to treatment. The standardized staining methods and monoclonal antibodies were used to detect cluster of differentiation antigens — CD138, CD56, CD20, CD117, cyclin D1, p53, kappa and lambda light chains.

Results: During the follow-up period of 49.6 (2–119.7) months in patients with increased levels of β2-microglobulin, higher International Prognostic Classification stage, with resistance to induction and higher relapse rate after first-line, a clonal lambda plasmocytes infiltration was observed. It also affected the response to induction with immunomodulatory drugs (IMiDs), but not bortezomib. The lowest response rate to IMiDs was noted in patients with CD117-lambda+ and CD56-lambda+ plasma cells. Clonal lambda hyperplasia connected with reduction in overall survival [hazard ratio (HR) 2.4; 95% confidence interval (CI): 0.96–5.92; p =0.047) and progression-free survival (PFS) (HR 4,32, 95% CI: 1.9–9.5; p =0.0002). The presence of plasmocytes with phenotype CD117-lambda+ (HR 3.37; 95% CI: 1.57–7.24; p =0.002) and CD56-lambda+ (HR 3,44; 95% CI: 1,63–7,27; p =0.001) contributed to PFS shortening.

Conclusions: In conclusions, BM biopsy with immunohistochemistry allow the identification of poorly prognostic patients with MM.

Get Citation

Keywords

multiple myeloma, histology, immunohistochemistry, prognosis

About this article
Title

The prognostic significance of bone marrow histological evaluation in patients with multiple myeloma

Journal

Acta Haematologica Polonica

Issue

Vol 52, No 5 (2021)

Article type

Original research article

Pages

493-503

Page views

3475

Article views/downloads

367

DOI

10.5603/AHP.2021.0088

Bibliographic record

Acta Haematol Pol 2021;52(5):493-503.

Keywords

multiple myeloma
histology
immunohistochemistry
prognosis

Authors

Andrzej Szczepaniak
Macie Kaźmierczak
Mieczysław Komarnicki
Anna Przybylowicz-Chalecka
Violetta Filas
Michał Michalak
Lidia Gil

References (48)
  1. Dmoszyńska A, Usnarska-Zubkiewicz L, Walewski J, et al. Zalecenia Polskiej Grupy Szpiczakowej dotyczące rozpoznawania i leczenia szpiczaka plazmocytowego oraz innych dyskrazji plazmocytowych na rok 2017. Acta Haematol Pol. 2017; 48(2): 55–103.
  2. Rajkumar S, Dimopoulos M, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014; 15(12): e538–e548.
  3. Rawstron AC, Orfao A, Beksac M, et al. European Myeloma Network. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica. 2008; 93(3): 431–438.
  4. Swerdlow SH, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J. WHO Classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Vol. 2. IARC Publication, Lyon 2017.
  5. Matsue K, Matsue Y, Kumata K, et al. Quantification of bone marrow plasma cell infiltration in multiple myeloma: usefulness of bone marrow aspirate clot with CD138 immunohistochemistry. Hematol Oncol. 2017; 35(3): 323–328.
  6. Jaffe ES, Arber DA, Campo E, Harris NL, Quintanilla-Martinez L. Hematoathology. Elsevier, Philadelphia 2016: 474–493.
  7. Thiele J, Kvasnicka F, Facchetti F, et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica, 2005. Haematologica. 2005; 90(8): 1128–1132.
  8. Al-Quran SZ, Yang L, Magill JM, et al. Assessment of bone marrow plasma cell infiltrates in multiple myeloma: the added value of CD138 immunohistochemistry. Hum Pathol. 2007; 38(12): 1779–1787.
  9. Yeung J, Chang H. Genomic aberrations and immunohistochemical markers as prognostic indicators in multiple myeloma. J Clin Pathol. 2008; 61(7): 832–836.
  10. Ng AP, Wei A, Bhurani D, et al. CD 138 immunostaining of bone marrow trephine specimens is the most sensitive method for quantifying marrow involvement in patients with plasma cell dyscrasias. Blood. 2005; 106(11): 5071–5071.
  11. Chang H, Samiee S, Yi QiL. Prognostic relevance of CD56 expression in multiple myeloma: a study including 107 cases treated with high-dose melphalan-based chemotherapy and autologous stem cell transplant. Leuk Lymphoma. 2006; 47(1): 43–47.
  12. Yavasoglu I, Sargin G, Kadikoylu G, et al. Immunohistochemical evaluation of CD20 expression in patients with multiple myeloma. Rev Bras Hematol Hemoter. 2015; 37(1): 34–37.
  13. Goto K, Takai T, Fukumoto T, et al. CD117 (KIT) is a useful immunohistochemical marker for differentiating porocarcinoma from squamous cell carcinoma. J Cutan Pathol. 2016; 43(3): 219–226.
  14. Padhi S, Varghese RG, Ramdas A. Cyclin D1 expression in multiple myeloma by immunohistochemistry: case series of 14 patients and literature review. Indian J Med Paediatr Oncol. 2013; 34(4): 283–291.
  15. Chng WJ, Price-Troska T, Gonzalez-Paz N, et al. Clinical significance of TP53 mutation in myeloma. Leukemia. 2007; 21(3): 582–584.
  16. Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009; 23(12): 2210–2221.
  17. Mikhael JR, Dingli D, Roy V, et al. Mayo Clinic. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013; 88(4): 360–376.
  18. Rajan AM, Rajkumar SV. Interpretation of cytogenetic results in multiple myeloma for clinical practice. Blood Cancer J. 2015; 5: e365.
  19. Greipp PR, San Miguel J, Durie BGM, et al. International staging system for multiple myeloma. J Clin Oncol. 2005; 23(15): 3412–3420.
  20. Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for Multiple Myeloma: a Report from International Myeloma Working Group. J Clin Oncol. 2015; 33(26): 2863–2869.
  21. Tran DN, Smith SA, Brown DA, et al. Polychromatic flow cytometry is more sensitive than microscopy in detecting small monoclonal plasma cell populations. Cytometry B Clin Cytom. 2017; 92(2): 136–144.
  22. Lee N, Moon SY, Lee JH, et al. Discrepancies between the percentage of plasma cells in bone marrow aspiration and BM biopsy: Impact on the revised IMWG diagnostic criteria of multiple myeloma. Blood Cancer J. 2017; 7(2): e530.
  23. Rajkumar SV, Fonseca R, Dispenzieri A, et al. Methods for estimation of bone marrow plasma cell involvement in myeloma: predictive value for response and survival in patients undergoing autologous stem cell transplantation. Am J Hematol. 2001; 68(4): 269–275.
  24. Rajkumar SV, Fonseca R, Lacy MQ, et al. Plasmablastic morphology is an independent predictor of poor survival after autologous stem-cell transplantation for multiple myeloma. J Clin Oncol. 1999; 17(5): 1551–1557.
  25. Hallgrimsdottir T, Porwit A, Björkholm M, et al. Bone marrow fibrosis in patients with multiple myeloma: a new prognostic factor for survival? Blood. 2013; 122(21): 1946–1946.
  26. Subramanian R, Basu D, Dutta TK. Significance of bone marrow fibrosis in multiple myeloma. Pathology. 2007; 39(5): 512–515.
  27. Sahara N, Takeshita A, Shigeno K, et al. Clinicopathological and prognostic characteristics of CD56-negative multiple myeloma. Br J Haematol. 2002; 117(4): 882–885.
  28. Yeung J, Samiee S, Yi Q, et al. Prognostic relevance of CD56 expression in patients with multiple myeloma treated with High-Dose Melphalan-Based Chemotherapy and Autologous Stem Cell Transplant. Blood. 2005; 106(11): 5086–5086.
  29. Pan Y, Wang H, Tao Q, et al. Absence of both CD56 and CD117 expression on malignant plasma cells is related with a poor prognosis in patients with newly diagnosed multiple myeloma. Leuk Res. 2016; 40: 77–82.
  30. Mateo G, Castellanos M, Rasillo A, et al. Genetic abnormalities and patterns of antigenic expression in multiple myeloma. Clin Cancer Res. 2005; 11(10): 3661–3667.
  31. Bataille R, Pellat-Deceunynck C, Robillard N, et al. CD117 (c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis. Leuk Res. 2008; 32(3): 379–382.
  32. Schmidt-Hieber M, Pérez-Andrés M, Paiva B, et al. CD117 expression in gammopathies is associated with an altered maturation of the myeloid and lymphoid hematopoietic cell compartments and favorable disease features. Haematologica. 2011; 96(2): 328–332.
  33. Ceran F, Falay M, Dağdaş S, et al. The assessment of CD56 and CD117 expressions at the time of the diagnosis in multiple myeloma patients. Turk J Haematol. 2017; 34(3): 226–232.
  34. Robillard N, Avet-Loiseau H, Garand R, et al. CD20 is associated with a small mature plasma cell morphology and t(11;14) in multiple myeloma. Blood. 2003; 102(3): 1070–1071.
  35. Quinn J, Percy L, Glassford J, et al. CD20-positive multiple myeloma — differential expression of cyclins D1 and D2 suggests a heterogeneous disease. Br J Haematol. 2010; 149(1): 156–159.
  36. Fernández de Larrea C, Kyle RA, Durie BGM, et al. International Myeloma Working Group. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group. Leukemia. 2013; 27(4): 780–791.
  37. Dispenzieri A, Kyle RA, Katzmann JA, et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood. 2008; 111(2): 785–789.
  38. Kyrtsonis MC, Vassilakopoulos TP, Kafasi N, et al. Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma. Br J Haematol. 2007; 137(3): 240–243.
  39. Shustik C, Bergsagel DE, Pruzanski W. Kappa and lambda light chain disease: survival rates and clinical manifestations. Blood. 1976; 48(1): 41–51.
  40. Kozlowski P, Montgomery S, Befekadu R, et al. The risk of renal disease is increased in lambda myeloma with bone marrow amyloid deposits. J Blood Med. 2017; 8: 29–34.
  41. Shameem M, Akhtar J, Bhargava R, et al. Lambda light chain multiple myeloma presenting as pleural mass. Respiratory Medicine CME. 2011; 4(1): 12–14.
  42. Morgan GJ, Davies F, Gregory W, et al. The addition of thalidomide to the induction treatment of newly presenting myeloma patients increases the CR rate which is likely to translate into improved PFS and OS. Blood. 2009; 114(22): 352–352.
  43. Munehiko A, Sameshima Y, Oda T, et al. [Factors affecting the response of thalidomide therapy for patients with multiple myeloma] [Article in Japanese]. Rinsho Ketsueki. 2010; 51(3): 189–195.
  44. Avet-Loiseau H, Leleu X, Roussel M, et al. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol. 2010; 28(30): 4630–4634.
  45. El-Ghammaz AMS, Abdelwahed E. Bortezomib-based induction improves progression-free survival of myeloma patients harboring 17p deletion and/or t(4;14) and overcomes their adverse prognosis. Ann Hematol. 2016; 95(8): 1315–1321.
  46. San Miguel JF, Schlag R, Khuageva NK, et al. VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008; 359(9): 906–917.
  47. Rosiñol L, Oriol A, Teruel AI, et al. Programa para el Estudio y la Terapéutica de las Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) group. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012; 120(8): 1589–1596.
  48. Tacchetti P, Pantani L, Stefano VDe, et al. Superior PFS2 with VTD vs TD for newly diagnosed, transplant eligible, multiple myeloma (MM) patients: updated analysis of Gimema MMY-3006 study. Blood. 2014; 124(21): 196–196.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Via Medica Publishers

ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
phone +48 58 320 94 94, fax+48 58 320 94 60,

e-mail: journals@viamedica.pl