Monoclonal gammopathy of undetermined significance natural history, complications and prognosis: Difference between revisions

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==Natural History==
==Natural History==
==Complications==
==Complications==
The following are frequent complications of [[Monoclonal gammopathy of undetermined significance]]
*Fractures specially in lumbar vertebrae<ref name="pmid16848794">{{cite journal |vauthors=Pepe J, Petrucci MT, Nofroni I, Fassino V, Diacinti D, Romagnoli E, Minisola S |title=Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance |journal=Br. J. Haematol. |volume=134 |issue=5 |pages=485–90 |date=September 2006 |pmid=16848794 |doi=10.1111/j.1365-2141.2006.06217.x |url=}}</ref><ref name="pmid14753733">{{cite journal |vauthors=Melton LJ, Rajkumar SV, Khosla S, Achenbach SJ, Oberg AL, Kyle RA |title=Fracture risk in monoclonal gammopathy of undetermined significance |journal=J. Bone Miner. Res. |volume=19 |issue=1 |pages=25–30 |date=January 2004 |pmid=14753733 |doi=10.1359/JBMR.0301212 |url=}}</ref><ref name="pmid16925792">{{cite journal |vauthors=Gregersen H, Jensen P, Gislum M, Jørgensen B, Sørensen HT, Nørgaard M |title=Fracture risk in patients with monoclonal gammopathy of undetermined significance |journal=Br. J. Haematol. |volume=135 |issue=1 |pages=62–7 |date=October 2006 |pmid=16925792 |doi=10.1111/j.1365-2141.2006.06269.x |url=}}</ref><ref name="pmid20610813">{{cite journal |vauthors=Kristinsson SY, Tang M, Pfeiffer RM, Björkholm M, Blimark C, Mellqvist UH, Wahlin A, Turesson I, Landgren O |title=Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study |journal=Blood |volume=116 |issue=15 |pages=2651–5 |date=October 2010 |pmid=20610813 |pmc=3324256 |doi=10.1182/blood-2010-04-282848 |url=}}</ref>
*Fractures specially in lumbar vertebrae<ref name="pmid16848794">{{cite journal |vauthors=Pepe J, Petrucci MT, Nofroni I, Fassino V, Diacinti D, Romagnoli E, Minisola S |title=Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance |journal=Br. J. Haematol. |volume=134 |issue=5 |pages=485–90 |date=September 2006 |pmid=16848794 |doi=10.1111/j.1365-2141.2006.06217.x |url=}}</ref><ref name="pmid14753733">{{cite journal |vauthors=Melton LJ, Rajkumar SV, Khosla S, Achenbach SJ, Oberg AL, Kyle RA |title=Fracture risk in monoclonal gammopathy of undetermined significance |journal=J. Bone Miner. Res. |volume=19 |issue=1 |pages=25–30 |date=January 2004 |pmid=14753733 |doi=10.1359/JBMR.0301212 |url=}}</ref><ref name="pmid16925792">{{cite journal |vauthors=Gregersen H, Jensen P, Gislum M, Jørgensen B, Sørensen HT, Nørgaard M |title=Fracture risk in patients with monoclonal gammopathy of undetermined significance |journal=Br. J. Haematol. |volume=135 |issue=1 |pages=62–7 |date=October 2006 |pmid=16925792 |doi=10.1111/j.1365-2141.2006.06269.x |url=}}</ref><ref name="pmid20610813">{{cite journal |vauthors=Kristinsson SY, Tang M, Pfeiffer RM, Björkholm M, Blimark C, Mellqvist UH, Wahlin A, Turesson I, Landgren O |title=Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study |journal=Blood |volume=116 |issue=15 |pages=2651–5 |date=October 2010 |pmid=20610813 |pmc=3324256 |doi=10.1182/blood-2010-04-282848 |url=}}</ref>
*Thromboembolic phenomena<ref name="pmid15367409">{{cite journal |vauthors=Sallah S, Husain A, Wan J, Vos P, Nguyen NP |title=The risk of venous thromboembolic disease in patients with monoclonal gammopathy of undetermined significance |journal=Ann. Oncol. |volume=15 |issue=10 |pages=1490–4 |date=October 2004 |pmid=15367409 |doi=10.1093/annonc/mdh385 |url=}}</ref><ref name="pmid17875234">{{cite journal |vauthors=Auwerda JJ, Sonneveld P, de Maat MP, Leebeek FW |title=Prothrombotic coagulation abnormalities in patients with paraprotein-producing B-cell disorders |journal=Clin Lymphoma Myeloma |volume=7 |issue=7 |pages=462–6 |date=July 2007 |pmid=17875234 |doi= |url=}}</ref>
*Thromboembolic phenomena<ref name="pmid15367409">{{cite journal |vauthors=Sallah S, Husain A, Wan J, Vos P, Nguyen NP |title=The risk of venous thromboembolic disease in patients with monoclonal gammopathy of undetermined significance |journal=Ann. Oncol. |volume=15 |issue=10 |pages=1490–4 |date=October 2004 |pmid=15367409 |doi=10.1093/annonc/mdh385 |url=}}</ref><ref name="pmid17875234">{{cite journal |vauthors=Auwerda JJ, Sonneveld P, de Maat MP, Leebeek FW |title=Prothrombotic coagulation abnormalities in patients with paraprotein-producing B-cell disorders |journal=Clin Lymphoma Myeloma |volume=7 |issue=7 |pages=462–6 |date=July 2007 |pmid=17875234 |doi= |url=}}</ref>
*Hypercoaguable state<ref name="pmid20299513">{{cite journal |vauthors=Kristinsson SY, Pfeiffer RM, Björkholm M, Goldin LR, Schulman S, Blimark C, Mellqvist UH, Wahlin A, Turesson I, Landgren O |title=Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study |journal=Blood |volume=115 |issue=24 |pages=4991–8 |date=June 2010 |pmid=20299513 |pmc=2890150 |doi=10.1182/blood-2009-11-252072 |url=}}</ref><ref name="pmid17875234">{{cite journal |vauthors=Auwerda JJ, Sonneveld P, de Maat MP, Leebeek FW |title=Prothrombotic coagulation abnormalities in patients with paraprotein-producing B-cell disorders |journal=Clin Lymphoma Myeloma |volume=7 |issue=7 |pages=462–6 |date=July 2007 |pmid=17875234 |doi= |url=}}</ref>
*Hypercoaguable state<ref name="pmid20299513">{{cite journal |vauthors=Kristinsson SY, Pfeiffer RM, Björkholm M, Goldin LR, Schulman S, Blimark C, Mellqvist UH, Wahlin A, Turesson I, Landgren O |title=Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study |journal=Blood |volume=115 |issue=24 |pages=4991–8 |date=June 2010 |pmid=20299513 |pmc=2890150 |doi=10.1182/blood-2009-11-252072 |url=}}</ref><ref name="pmid17875234">{{cite journal |vauthors=Auwerda JJ, Sonneveld P, de Maat MP, Leebeek FW |title=Prothrombotic coagulation abnormalities in patients with paraprotein-producing B-cell disorders |journal=Clin Lymphoma Myeloma |volume=7 |issue=7 |pages=462–6 |date=July 2007 |pmid=17875234 |doi= |url=}}</ref>
*Development of secondary cancers<ref name="pmid22310913">{{cite journal |vauthors=Thomas A, Mailankody S, Korde N, Kristinsson SY, Turesson I, Landgren O |title=Second malignancies after multiple myeloma: from 1960s to 2010s |journal=Blood |volume=119 |issue=12 |pages=2731–7 |date=March 2012 |pmid=22310913 |pmc=3327452 |doi=10.1182/blood-2011-12-381426 |url=}}</ref><ref name="pmid21795746">{{cite journal |vauthors=Mailankody S, Pfeiffer RM, Kristinsson SY, Korde N, Bjorkholm M, Goldin LR, Turesson I, Landgren O |title=Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS) |journal=Blood |volume=118 |issue=15 |pages=4086–92 |date=October 2011 |pmid=21795746 |pmc=3204729 |doi=10.1182/blood-2011-05-355743 |url=}}</ref>
*Development of secondary cancers eg. acute myeloid leukemia and myelodysplastic syndromes<ref name="pmid22310913">{{cite journal |vauthors=Thomas A, Mailankody S, Korde N, Kristinsson SY, Turesson I, Landgren O |title=Second malignancies after multiple myeloma: from 1960s to 2010s |journal=Blood |volume=119 |issue=12 |pages=2731–7 |date=March 2012 |pmid=22310913 |pmc=3327452 |doi=10.1182/blood-2011-12-381426 |url=}}</ref><ref name="pmid21795746">{{cite journal |vauthors=Mailankody S, Pfeiffer RM, Kristinsson SY, Korde N, Bjorkholm M, Goldin LR, Turesson I, Landgren O |title=Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS) |journal=Blood |volume=118 |issue=15 |pages=4086–92 |date=October 2011 |pmid=21795746 |pmc=3204729 |doi=10.1182/blood-2011-05-355743 |url=}}</ref>


==Prognosis==
==Prognosis==


* MGUS may be considered a pre-malignant condition, given the possibility of transformation into multiple myeloma.  However, because the condition tends to occur in the elderly, and because the rate of progression is slow, only a small proportion of people with MGUS 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%.<ref>{{cite journal | author = Bladé J | title = Clinical practice. Monoclonal gammopathy of undetermined significance. | journal = N Engl J Med | volume = 355 | issue = 26 | pages = 2765-70 | year = 2006 | id =PMID 17192542 [http://content.nejm.org/cgi/content/short/355/26/2765 Abstract]}}</ref>
* MGUS may be considered a pre-malignant condition, given the possibility of transformation into multiple myeloma.  However, because the condition tends to occur in the elderly, and because the rate of progression is slow, only a small proportion of people with MGUS 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%.<ref>{{cite journal | author = Bladé J | title = Clinical practice. Monoclonal gammopathy of undetermined significance. | journal = N Engl J Med | volume = 355 | issue = 26 | pages = 2765-70 | year = 2006 | id =PMID 17192542 [http://content.nejm.org/cgi/content/short/355/26/2765 Abstract]}}</ref>


* The annual risk of progressing to multiple myeloma is around 1&ndash;2% a year.  Kyle ''et al'' studied the prevalence of myeloma in a population-wide cohort in Olmsted County, Minnesota. They found that the prevalence of MGUS was 3.2% in people above 50, with a slight male predominance (4.0% vs. 2.7%). Prevalence increased with age: of 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 was &lt;1 g/dl, while only a very small group had levels over 2 g/dl.<ref name="Kyle">{{cite journal | author=Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, Dispenzieri A, Katzmann JA, Melton LJ 3rd. | title=Prevalence of monoclonal gammopathy of undetermined significance | journal=N Engl J Med | year=2006 | month=28 December | volume=354| pages=1362-9 | id=PMID 16571879}}</ref>
* The annual risk of progressing to multiple myeloma is around 1&ndash;2% a year.  The prevalence of myeloma in a population-wide cohort in Olmsted County, Minnesota. They found that the prevalence of MGUS was 3.2% in people above 50, with a slight male predominance (4.0% vs. 2.7%). Prevalence increased with age: of 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 was &lt;1 g/dl, while only a very small group had levels over 2 g/dl.<ref name="Kyle">{{cite journal | author=Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, Dispenzieri A, Katzmann JA, Melton LJ 3rd. | title=Prevalence of monoclonal gammopathy of undetermined significance | journal=N Engl J Med | year=2006 | month=28 December | volume=354| pages=1362-9 | id=PMID 16571879}}</ref>


* In addition to multiple myeloma, MGUS may also progress to [[Waldenström's macroglobulinemia]], primary [[amyloidosis]], [[B-cell lymphoma]], or[[chronic lymphocytic leukemia]]. <font color="#777777">'</font>
* In addition to multiple myeloma, MGUS may also progress to [[Waldenström's macroglobulinemia]], primary [[amyloidosis]], [[B-cell lymphoma]], or[[chronic lymphocytic leukemia]]. <font color="#777777">'</font>

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Overview

Natural History

Complications

The following are frequent complications of Monoclonal gammopathy of undetermined significance

  • Fractures specially in lumbar vertebrae[1][2][3][4]
  • Thromboembolic phenomena[5][6]
  • Hypercoaguable state[7][6]
  • Development of secondary cancers eg. acute myeloid leukemia and myelodysplastic syndromes[8][9]

Prognosis

  • MGUS may be considered a pre-malignant condition, given the possibility of transformation into multiple myeloma. However, because the condition tends to occur in the elderly, and because the rate of progression is slow, only a small proportion of people with MGUS 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%.[10]
  • The annual risk of progressing to multiple myeloma is around 1–2% a year. The prevalence of myeloma in a population-wide cohort in Olmsted County, Minnesota. They found that the prevalence of MGUS was 3.2% in people above 50, with a slight male predominance (4.0% vs. 2.7%). Prevalence increased with age: of 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 was <1 g/dl, while only a very small group had levels over 2 g/dl.[11]

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 6.0 6.1 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ Bladé J (2006). "Clinical practice. Monoclonal gammopathy of undetermined significance". N Engl J Med. 355 (26): 2765–70. PMID 17192542 Abstract.
  11. ↑ 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)

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