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]
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]
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%.[11]
- 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.[12]
- 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.
- ↑ 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
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