Clinical-Laboratory Significance of Myelofibrosis in Patients with Multiple Myeloma

Tatyana Yu. Dolgikh*, PhD; Yuliya A. D’yachkova; Natalya P. Domnikova, PhD, ScD; Nina A. Maltseva; Igor V. Kachesov

Institute of Regional Pathology and Pathomorphology of Siberian Branch of the RAMS Novosibirsk, Russian Federation.

*Corresponding author: Tatyana Yu. Dolgikh, PhD. Institute of Regional Pathology and Pathomorphology of Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia. E-mail:

Published: June 22, 2014.


Background: Currently, there are not many studies of correlations between myelofibrosis (MF) and clinical-laboratory data on multiple myeloma (MM).

Methods and Results: In our study, MF was evaluated according to the scale of the European consensus (2005). Additionally, we used an automated morphometric study. The inverse correlations between the prevalence of MF and the total number of erythroid cells and megakaryocytes, as well as hemoglobin level were found. The total relative area of fibrosis tissue (Srel.fibr.tis.) in initial and advanced MF>20% was associated with anemia requiring a blood transfusion.The development of severe anemia was observed in patients with a greater relative area of ​​ Srel.fibr.tis. The direct correlations between Srel.fibr.tis. and relative area of tumor tissue (Srel.tum.tis.), between Srel.fibr.tis. and the level of total serum protein, between Srel.fibr.tis. and daily proteinuria were found both in initial and in advanced MF. Additionally, a direct correlation between Srel.fibr.tis. and the number of plasma cells was revealed in initial MF. Greater Srel.fibr.tis. in initial and advanced MF was found in patients with chronic renal failure.

Conclusion: The clinical-laboratory significance of MF in MM is an inhibition of erythroid cells and megakaryocytes and development of anemia. The relative area of ​​fibrous tissue is a marker of tumor volume and tumor progression.

myelofibrosis (MF); multiple myeloma (MM); anemia; tumor progression.

1.  Babarović E, Valković T, ŠtifterS,  Budisavljević I, Seili-Bekafigo M, Duletić-Načinović A, Assessment of bone marrow fibrosis and angiogenesis in monitoring patients with multiple myeloma. Am J Clin Pathol 2012;137(6):870-8.

2. Subramanian R, Basu D, Dutta TK. Significance of bone marrow fibrosis in multiple myeloma.  Pathology 2007;39(5):512-5.

3. Singhal N, Singh T, Singh ZN, Shome DK, Gaiha M. Histomorphology of multiple myeloma on bone marrow biopsy. Indian J Pathol Microbiol 2004; 47(3):359-63.

4. Chen HS, Liu EB, Wang TT, Yang RC, Fang LH, Yang QY. et al. Morphologic and clinical study of 131 cases of plasma cell myeloma. Zhonghua Bing Li Xue Za Zhi 2004; 33(1):44-8. [Article in Chinese].

5. Abildgaard N, Bendix-Hansen K, Kristensen JE, Vejlgaard T, Ristelli L, Nielsen JL, et al. Bone marrow fibrosis and disease activity in multiple myeloma monitored by the aminoterminal propeptide of procollagen III in serum. Br J Haematol 1997; 99(3):641-8.

6. Huang YW, Hamilton A, Arnuk OJ, Chaftari P, Chemaly R. Current drug therapy for multiple myeloma. Drugs1999; 57(4):485-506.

7. Russian clinical practice guidelines for the diagnosis and treatment of lymphoproliferative diseases. Edit  by Professor I. Poddubnaya and Professor VG Savchenko. M.: Media Medica; 2013.

8. Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer1975;36(3):842-54.

9. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009; 23(1):3–9.

10. Bladé J, Samson D, Reece D, Apperley J, Orkstand BJ, Gahrton G, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol1998;102(5):1115-23.

11. Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 2005; 90:1128–32.

12. Tadmor T, Shvidel L, Aviv A, Ruchlemer R, Bairey O, Yuklea M, et al. Significance of bone marrow reticulin fibrosis in chronic lymphocytic leukemia at diagnosis: a study of 176 patients with prognostic implications. Cancer 2013;119 (10):1853-9.

13. Frassanito MA, Rao L, Moschetta M, Ria R, Marzo L Di, Luisi AD, et al. Bone marrow fibroblasts parallel multiple myeloma progression in patients and mice: in vitro and in vivo studies. Leukemia 2014;28(4):904-16.

14. Kuter DJ, Bain B, Mufti G, Bagg A, Hasserjian RP. Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol 2007;139 (3):351-362.

15. Lauta VM. A review of the cytokine network in multiple myeloma: diagnostic, prognostic, and therapeutic implications. Cancer2003; 97(10):2440-52.

16. Huang X., Pierce LJ, Chen GL, Chang KT, Spanqrude GJ, Prchal JT. Erythropoietin receptor signaling regulates both erythropoiesis and megakaryopoiesis in vivo. Blood Cells Mol Dis 2010;144(1):1-6.

17. Petrusenko EE, Domnikova NP, Nepomnyashchikh GI, Mal'tseva NA. Changes in bone marrow and peripheral compartments of the erythron under the effect of tumor cells in indolent non-Hodgkin lymphomas and multiple myeloma. Bull Exp Biol Med 2010;150(3):359-64.

18. Gangat N, Wolanskyj AP. Anemia of chronic disease. Semin Hematol 2013; 50(3):232-8.

19. Wynn TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest 2007; 117(3):524-9.

20. Chavynchak RB, Rekhtina IG. Prognostic factors in multiple myeloma complicated with renal failure. Ter Arkh 2008; 80(1):84-8. [Article in Russian].

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Int J Biomed. 2014; 4(2):72-75. © 2014 International Medical Research and Development Corporation. All rights reserved.