Monoclonal gammopathy of undetermined significance natural history, complications and prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2] Muhammad Saad, M.B.B.S.[3]
Overview
Frequent complications of Monoclonal gammopathy of undetermined significance include fractures specially in lumbar vertebrae and thromboembolic phenomena. MGUS, is considered as a pre-malignant condition, and its transformation to multiple myeloma. However, as it mostly occurs in elderly, and its slow rate of progression, only a small proportion of people go on to develop a haematological malignancy. In patients with MGUS, although the actuarial risk of myeloma at 25 years of follow-up is 30%, the actual risk (when competing causes of death are taken into account) is only 11%.
Natural History
Each patient with MGUS should be followed up for progression to multiple myeloma, it can be considered as a pre-malignant condition. The probability for malignant transformation was 6.1, 15.4 and 31.3% at 5, 10 and 20 years, respectively. 157 patients (59.7%), 119 (45.3%) of whom with no increase and 38 (14.4%) with an increase in serum M-component, died of causes unrelated to MGUS and without development of any plasma cell proliferative disease; 47 patients (17.9%) were still alive without increase in M-component; 11 patients (4.1%) were still alive and at follow-up presented values of serum M-component > 30 g/l without any evidence of plasma cell proliferative or lymphoproliferative disease; 48 patients (18.3%) developed multiple myeloma (35 cases, 13.1%), solitary plasmacytoma of the bone (2 cases, 0.8%), macroglobulinaemia (4 cases, 1.6%), malignant lymphoma (3 cases, 1.2%), amyloidosis (2 cases, 0.8%), chronic lymphocytic leukaemia (1 case, 0.4%), and plasma cell leukaemia (1 case, 0.4%).[1]
Complications
The following are frequent complications of Monoclonal gammopathy of undetermined significance
- Fractures specially in lumbar vertebrae[2][3][4][5]
- Thromboembolic phenomena[6][7]
- Hypercoaguable state[8][7]
- Development of secondary cancers eg. acute myeloid leukemia and myelodysplastic syndromes[9][10]
- Autoimmune diseases[11]
- Increased mortality[12]
Prognosis
- MGUS, is considered as a pre-malignant condition, and its transformation to multiple myeloma. However, as it mostly occurs in elderly, and its slow rate of progression, only a small proportion of people go on to develop a hematological malignancy. In patients with MGUS, although the actuarial risk of myeloma at 25 years of follow-up is 30%, the actual risk (when competing causes of death are taken into account) is only 11%.[13]
- The annual risk of progressing to multiple myeloma is around 1–2% a year. The prevalence of MGUS was 3.2% in people above 50, with a slight male predominance (4.0% vs. 2.7%). Prevalence increases with age. In people over 70 up to 5.3% had MGUS, while in the over-85 age group the prevalence was 7.5%. In the majority of cases (63.5%), the paraprotein level reported as <1 g/dl, while only a very small group reported levels over 2 g/dl.[14]
- In addition to multiple myeloma, MGUS may also progress to Waldenström's macroglobulinemia, primary amyloidosis, B-cell lymphoma, orchronic lymphocytic leukemia. '
References
- ↑ Pasqualetti P, Festuccia V, Collacciani A, Casale R (1997). "The natural history of monoclonal gammopathy of undetermined significance. A 5- to 20-year follow-up of 263 cases". Acta Haematol. 97 (3): 174–9. doi:10.1159/000203676. PMID 9066713.
- ↑ Pepe J, Petrucci MT, Nofroni I, Fassino V, Diacinti D, Romagnoli E, Minisola S (September 2006). "Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance". Br. J. Haematol. 134 (5): 485–90. doi:10.1111/j.1365-2141.2006.06217.x. PMID 16848794.
- ↑ Melton LJ, Rajkumar SV, Khosla S, Achenbach SJ, Oberg AL, Kyle RA (January 2004). "Fracture risk in monoclonal gammopathy of undetermined significance". J. Bone Miner. Res. 19 (1): 25–30. doi:10.1359/JBMR.0301212. PMID 14753733.
- ↑ Gregersen H, Jensen P, Gislum M, Jørgensen B, Sørensen HT, Nørgaard M (October 2006). "Fracture risk in patients with monoclonal gammopathy of undetermined significance". Br. J. Haematol. 135 (1): 62–7. doi:10.1111/j.1365-2141.2006.06269.x. PMID 16925792.
- ↑ Kristinsson SY, Tang M, Pfeiffer RM, Björkholm M, Blimark C, Mellqvist UH, Wahlin A, Turesson I, Landgren O (October 2010). "Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study". Blood. 116 (15): 2651–5. doi:10.1182/blood-2010-04-282848. PMC 3324256. PMID 20610813.
- ↑ Sallah S, Husain A, Wan J, Vos P, Nguyen NP (October 2004). "The risk of venous thromboembolic disease in patients with monoclonal gammopathy of undetermined significance". Ann. Oncol. 15 (10): 1490–4. doi:10.1093/annonc/mdh385. PMID 15367409.
- ↑ 7.0 7.1 Auwerda JJ, Sonneveld P, de Maat MP, Leebeek FW (July 2007). "Prothrombotic coagulation abnormalities in patients with paraprotein-producing B-cell disorders". Clin Lymphoma Myeloma. 7 (7): 462–6. PMID 17875234.
- ↑ Kristinsson SY, Pfeiffer RM, Björkholm M, Goldin LR, Schulman S, Blimark C, Mellqvist UH, Wahlin A, Turesson I, Landgren O (June 2010). "Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study". Blood. 115 (24): 4991–8. doi:10.1182/blood-2009-11-252072. PMC 2890150. PMID 20299513.
- ↑ Thomas A, Mailankody S, Korde N, Kristinsson SY, Turesson I, Landgren O (March 2012). "Second malignancies after multiple myeloma: from 1960s to 2010s". Blood. 119 (12): 2731–7. doi:10.1182/blood-2011-12-381426. PMC 3327452. PMID 22310913.
- ↑ Mailankody S, Pfeiffer RM, Kristinsson SY, Korde N, Bjorkholm M, Goldin LR, Turesson I, Landgren O (October 2011). "Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS)". Blood. 118 (15): 4086–92. doi:10.1182/blood-2011-05-355743. PMC 3204729. PMID 21795746.
- ↑ Sverrisdottir I, Thorsteinsdottir S, Rognvaldsson S, Aspelund T, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Thorsteinsdóttir I, Sveinsdottir SV, Palmason R, Olafsson I, Sigurdsson F, Thordardóttir AR, Eythorsson E, Jonsson A, Palsson R, Indridason OS, Gislason GK, Olafsson A, Sigurdsson J, Steingrímsdóttir H, Einarsson Long T, Hultcrantz M, Durie BG, Harding S, Landgren O, Kristinsson SY, Love TJ (June 2024). "Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance : An Analysis From a Population-Based Screening Study". Ann Intern Med. 177 (6): 711–718. doi:10.7326/M23-2867. PMID 38768457 Check
|pmid=value (help). - ↑ Ji M, Huber JH, Schoen MW, Sanfilippo KM, Colditz GA, Wang SY, Chang SH (September 2023). "Mortality in the US Populations With Monoclonal Gammopathy of Undetermined Significance". JAMA Oncol. 9 (9): 1293–1295. doi:10.1001/jamaoncol.2023.2278. PMID 37498610 Check
|pmid=value (help). - ↑ Bladé J (2006). "Clinical practice. Monoclonal gammopathy of undetermined significance". N Engl J Med. 355 (26): 2765–70. PMID 17192542 Abstract.
- ↑ Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, Dispenzieri A, Katzmann JA, Melton LJ 3rd. (2006). "Prevalence of monoclonal gammopathy of undetermined significance". N Engl J Med. 354: 1362–9. PMID 16571879. Unknown parameter
|month=ignored (help)