Clinical Manifestations, Immunoglobulin Subtypes, and Chromosomal Translocations in Multiple Myeloma: A Tertiary Care Center Study from Pakistan

Mustajab Alam; Hamid Nawaz  Tipu; Muhammad Aftab Hassan; Muhammad Hussain; Muhammad Zain Ul Abdeen

doi:10.51253/pafmj.v76i4.13204

Authors

Mustajab Alam Department of Immunology, Armed Forces Institute of Pathology /National University of Medical Sciences (NUMS) Rawalpindi Pakistan
Hamid Nawaz Tipu Department of Immunology, Armed Forces Institute of Pathology /National University of Medical Sciences (NUMS) Rawalpindi Pakistan
Muhammad Aftab Hassan Department of Immunology, Armed Forces Institute of Pathology /National University of Medical Sciences (NUMS) Rawalpindi Pakistan
Muhammad Hussain Department of Immunology, Armed Forces Institute of Pathology /National University of Medical Sciences (NUMS) Rawalpindi Pakistan
Muhammad Zain Ul Abdeen Department of Immunology, Armed Forces Institute of Pathology /National University of Medical Sciences (NUMS) Rawalpindi Pakistan

DOI:

https://doi.org/10.51253/pafmj.v76i4.13204

Keywords:

Cytogenetic profiles, Multiple Myeloma, Plasma cell neoplasms

Abstract

Objective: To analyze the clinical manifestations, immunoglobulin subtypes, and chromosomal translocations in multiple myeloma patients at a tertiary care center in Rawalpindi, Pakistan.

Study Design: Retrospective descriptive study

Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology, NUMS, Rawalpindi, Pakistan, from Aug 2021 to Aug 2024.

Methodology: In this study, 100 symptomatic patients of multiple myeloma were included. Serum protein electrophoresis was performed to detect abnormal paraproteins produced by myeloma cells, followed by Immunofixation electrophoresis to characterize the type of abnormal paraproteins. Fluorescence in situ hybridization was used to detect chromosomal translocations and other genetic abnormalities in 38 patients. Chi-square test was applied to find any significant association between identified translocations and clinical features. A p-value less than 0.05 was deemed statistically significant.

Results: Out of 100 cases, the majority of participants were male (64.0%) with ages ranging from 38 – 82 years. Chromosomal analysis by FISH revealed that most frequent translocations were t(4;14) in 5(13.2%) patients, t(11;14) in 4(10.5%), and t(14;18) in 3(7.9%) patients. A co-occurrence of t(4;14), del(1p32), and gain(1q21) was observed in 3(7.9%) patients. Regarding immunoglobulin isotypes, IgG was present in 66 patients (65.0%), IgA was present in 27.0% of cases, while light chain myeloma was found in 6% of cases.

Conclusions: Multiple myeloma is a complex hematologic malignancy requiring comprehensive evaluation of clinical presentations, immunoglobulin subtypes, and genetic abnormalities for effective patient management. Continued research is crucial for enhancing therapeutic strategies and improving the quality of life for affected patients

Downloads

Download data is not yet available.

Author Biography

Mustajab Alam, Department of Immunology, Armed Forces Institute of Pathology /National University of Medical Sciences (NUMS) Rawalpindi Pakistan

References

1. Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol 2016; 43(6): 676-681. https://doi.org/10.1053/j.seminoncol.2016.11.004

2. Mikhael J, Bhutani M, Cole CE. Multiple myeloma for the primary care provider: a practical review to promote earlier diagnosis among diverse populations. Am J Med 2023; 136(1): 33-41.

https://doi:10.1016/j.amjmed.2022.08.030

3. Furukawa Y, Kikuchi J. Molecular pathogenesis of multiple myeloma. Int J Clin Oncol 2015;20(3):413-422. https://doi:10.1007/s10147-015-0837-0

4. Shah UA, Mailankody S. Emerging immunotherapies in multiple myeloma. BMJ 2020; 370: m3176.

https://doi:10.1136/bmj.m3176

6. Faiman B, Valent J. Assessment and monitoring of patients receiving chemotherapy for multiple myeloma: strategies to improve outcomes. Blood Lymphat Cancer Targets Ther 2016; 6: 21-35. https://doi:10.2147/BLCTT.S90764

5. Landgren O, Rajkumar SV. New developments in diagnosis, prognosis, and assessment of response in multiple myeloma. Clin Cancer Res 2016; 22(22): 5428-5433. https://doi:10.1158/1078-0432.CCR-16-0866

7. Zhu S, Li W, Lin M, Li T. Serum protein electrophoresis and immunofixation electrophoresis detection in multiple myeloma. J Coll Physicians Surg Pak 2021; 31(7): 864-867.

https://doi:10.29271/jcpsp.2021.07.864

8. Gay F, Bertuglia G, Mina R. A rational approach to functional high-risk myeloma. Hematology Am Soc Hematol Educ Program 2023; 2023(1): 433-442. https://doi:10.1182/hematology.2023000443

9. Sullivan KM, Dean A, Soe MM. OpenEpi: a web-based epidemiologic and statistical calculator for public health. Public Health Rep 2009; 124(3): 471-474. https://doi:10.1177/003335490912400320

10.Wang S, Xu L, Feng J, Liu Y, Liu L, Wang J, et al. Prevalence and incidence of multiple myeloma in urban area in China: a national population-based analysis. Front Oncol 2019; 9: 1513. https://doi:10.3389/fonc.2019.01513

11.Manier S, Salem KZ, Park J, Landau DA, Getz G, Ghobrial IM. Genomic complexity of multiple myeloma and its clinical implications. Nat Rev Clin Oncol 2017; 14(2): 100-113. https://doi:10.1038/nrclinonc.2016.122

12. Bal S, Giri S, Godby KN, Costa LJ. Revisiting the impact of immunoglobulin isotypes in multiple myeloma. Ann Hematol 2022; 101(4): 825-829. https://doi:10.1007/s00277-022-04783-1

13. Nair B, Shaughnessy JD Jr, Zhou Y, Astrid-Cartron M, Qu P, van Rhee F, et al. Gene expression profiling of plasma cells at myeloma relapse from tandem transplantation trial Total Therapy 2 predicts subsequent survival. Blood 2009; 113(26): 6572-6575.

https://doi:10.1182/blood-2009-02-207803

14. Jian Y, Chen X, Zhou H, Zhu W, Liu N, Geng C, et al. Prognostic impact of cytogenetic abnormalities in multiple myeloma: a retrospective analysis of 229 patients. Medicine 2016; 95(19): e3521. https://doi:10.1097/MD.0000000000003521

15. Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol 2020; 95(5): 548-567. https://doi:10.1002/ajh.25791

16. Orzetti S, Tommasi F, Bertola A, Bortolin G, Caccin E, Cecco S, et al. Genetic therapy and molecular targeted therapy in oncology: safety, pharmacovigilance, and perspectives for research and clinical practice. Int J Mol Sci 2022; 23(6): 3012. https://doi:10.3390/ijms23063012

17. Cardona-Benavides IJ, de Ramón C, Gutiérrez NC. Genetic abnormalities in multiple myeloma: prognostic and therapeutic implications. Cells. 2021; 10(2): 336. https://doi:10.3390/cells10020336

18. Hagen P, Zhang J, Barton K. High-risk disease in newly diagnosed multiple myeloma: beyond the R-ISS and IMWG definitions. Blood Cancer J 2022; 12(5): 83.

https://doi:10.1038/s41408-022-00679-5

19. Zaheer S, Robert HM, Mahmood A, Mahmood R, Khurshid A, Khan N. Frequency of t(4;14) in multiple myeloma and its clinicopathological correlation. Pak Armed Forces Med J 2022; 72(Suppl 2): S103-S106. https://doi:10.51253/pafmj.v72iSUPPL-2.3384

20. Schavgoulidze A, Perrot A, Cazaubiel T, Leleu X, Montes L, Jacquet C, et al. Prognostic impact of translocation t(14;16) in multiple myeloma according to the presence of additional genetic lesions. Blood Cancer J 2023;1 3(1): 160.

https://doi:10.1038/s41408-023-00933-4

21. Hussain M, Mahmood A, Mahmood R, Iqbal H, Khurshid A, Khan N. Multiple myeloma-clinicopathological features and risk stratification. Pak Armed Forces Med J 2022; 72(Suppl 2): S95-S98. https://doi:10.51253/pafmj.v72iSUPPL-2.3100

22. Malard F, Neri P, Bahlis NJ, Terpos E, Moukalled N, Hungria VTM, et al. Multiple myeloma. Nat Rev Dis Primers 2024; 10(1): 45. https://doi:10.1038/s41572-024-00529-7

23. Bong IPN, Esa E. Molecular genetic aberrations in the pathogenesis of multiple myeloma. Asian Biomed 2023; 17(4): 152-162. https://doi:10.2478/abm-2023-0056