Monoclonal Proteinuria as a Prognostic Factor for Multiple Myeloma Patients with Intact Immunoglobulin Type

Dong Hoe Koo; Ji Seon Oh; Seong-Ho Choi; Hyun Gu Park; Sung Sook Lee; Min Kyoung Kim; Sun Jin Sym; Won-Ki Min; Shin Kim; Sheolwon Suh

doi:10.5045/kjh.2007.42.3.276

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Koo, Oh, Choi, Park, Lee, Kim, Sym, Min, Kim, and Suh: Monoclonal Proteinuria as a Prognostic Factor for Multiple Myeloma Patients with Intact Immunoglobulin Type

Original Article

Korean J Hematol 2007;42(3):276-282.

Published online: 19 September 2007

DOI: https://doi.org/10.5045/kjh.2007.42.3.276

Monoclonal Proteinuria as a Prognostic Factor for Multiple Myeloma Patients with Intact Immunoglobulin Type

Dong Hoe Koo, Ji Seon Oh, Seong-Ho Choi, Hyun Gu Park, Sung Sook Lee, Min Kyoung Kim, Sun Jin Sym, Won-Ki Min¹, Shin Kim, Sheolwon Suh

Departments of Internal Medicine, Seoul, Korea

¹Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to：Sheolwon Suh, M.D. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine 388-1, Pungnap 2-dong, Songpa-gu, Seoul 138-738, Korea Tel: ＋82-2-3010-3209, Fax: ＋82-2-3010-6961 E-mail: csuh@amc.seoul.kr

Received 13 July 2007 Revised 7 August 2007 Accepted 10 August 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Urine/serum protein electrophoresis (PEP) and immunofixation electrophoresis (IEP) for monoclonal protein (M-protein) are used for initial evaluation in patients with multiple myeloma. We evaluated the prognostic significance of M-proteinuria status and its association with other prognostic factors.

Methods:

Between December 2002 and December 2004, 64 de novo symptomatic multiple myeloma patients with intact immunoglobulin (Ig) type were divided into two groups according to their initial urine PEP/IEP findings.

Results:

Twenty-seven patients with undetectable or free light-chains only were classified into F group, and 37 with whole Ig with or without light-chains were classified into W group. The two groups were similar in sex, age, performance, azotemia, β2-microglobulin, stage and treatment, but M-protein concentration was significantly higher in the W than in F group (5.1 vs 1.3g/dL, P＜0.01). The overall response rate was significantly higher in F group than in W group (80.8% vs 63.6%, P=0.02), whereas the 2-year OS rate did not differ significantly between the groups (81.0% vs 57.7%, P=0.15).

Conclusion:

Monoclonal proteinuria is helpful in identifying patients with advanced disease and poorer prognosis in multiple myeloma.

Keywords: Multiple myeloma, Proteinuria, Prognosis

REFERENCES

1). Clark AD., Shetty A., Soutar R. Renal failure and multiple myeloma: pathogenesis and treatment of renal failure and management of underlying myeloma. Blood Rev. 1999. 13:79–90.

2). Honkanen E., Pettersson T., Teppo AM. Urinary alpha 1- and beta 2-microglobulin in light chain proteinuria. Clin Nephrol. 1995. 44:22–7.

3). Markowitz GS. Dysproteinemia and the kidney. Adv Anat Pathol. 2004. 11:49–63.

4). International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Hae-matol. 2003. 121:749–57.

5). Blade J., Samson D., Reece D, 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 Haematol. 1998. 102:1115–23.

6). Greipp PR., San Miguel J., Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005. 23:3412–20.

7). Anagnostopoulos A., Gika D., Symeonidis A, et al. Multiple myeloma in elderly patients: prognostic factors and outcome. Eur J Haematol. 2005. 75:370–5.

8). Kyle RA. Multiple myeloma: review of 869 cases. Mayo Clin Proc. 1975. 50:29–40.

9). Knudsen LM., Hippe E., Hjorth M., Holmberg E., Westin J. Renal function in newly diagnosed multiple myeloma—a demographic study of 1,353 patients. The Nordic Myeloma Study Group. Eur J Haematol. 1994. 53:207–12.

10). Rota S., Mougenot B., Baudouin B, et al. Multiple myeloma and severe renal failure: a clinicopathologic study of outcome and prognosis in 34 patients. Medicine (Baltimore). 1987. 66:126–37.

11). Tricot G., Alberts DS., Johnson C, et al. Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study. Clin Cancer Res. 1996. 2:947–52.

12). Tosi P., Zamagni E., Ronconi S, et al. Safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma and chronic renal failure. Leukemia. 2000. 14:1310–3.

13). San Miguel JF., Lahuerta JJ., Garcia-Sanz R, et al. Are myeloma patients with renal failure candidates for autologous stem cell transplantation? Hematol J. 2000. 1:28–36.

14). BladéJ. Fernández-Llama P., Bosch F, et al. Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution. Arch Intern Med. 1998. 158:1889–93.

15). Knudsen LM., Hjorth M., Hippe E. Renal failure in multiple myeloma: reversibility and impact on the prognosis. Eur J Haematol. 2000. 65:175–81.

16). Bazzi C., Petrini C., Rizza V, et al. Urinary excretion of IgG and alpha(1)-microglobulin predicts clinical course better than extent of proteinuria in membranous nephropathy. Am J Kidney Dis. 2001. 38:240–8.

17). Corso A., Zappasodi P., Pascutto C, et al. Urinary proteins in multiple myeloma: correlation with clinical parameters and diagnostic implications. Ann Hematol. 2003. 82:487–91.

18). Yun JP., Suh C., Lee E, et al. Comparison of serum beta 2-microglobulin and 24 hour urinary creatinine clearance as a prognostic factor in multiple myeloma. J Korean Med Sci. 2006. 21:639–44.

Fig. 1

Overall survival curves relative to M-proteinuria.

Table 1.

Patient demographic and clinical characteristics at baseline

	F group n (%)	W group n (%)	P value
No. of patients	27 (100.0%)	37 (100.0%)
No. of males	17 (63.0%)	17 (45.9%)	0.13
Median age (range)	59 yrs (42~77)	61 yrs (41∼82)	0.45
Median f/u time (range)	24.9 months (14.1∼37.4)
ECOG (PS) 1	21 (77.8%)	25 (67.6%)	0.54
2	4 (14.8%)	6 (16.2%)
3	2 (7.4%)	6 (16.2%)
ISS stage I	4 (14.8%)	1 (2.7%)	0.09
II	14 (51.9%)	16 (43.2%)
III	9 (33.3%)	20 (54.1%)

Abbreviations: PS, performance status; ISS, International staging system.

Table 2.

Patient laboratory characteristics at baseline

	F group median (range)	W group median (range)	P value
M-protein (g/dL)	1.3 (0.1∼6.2)	5.1 (0.9∼10.5)	*0.001*
BJ protein (mg/24 hr)	53.2 (0∼6,980)	385.1 (9∼6,044)	0.78
Hb (g/dL)	10.5 (6.3∼14.0)	8.4 (4.7∼13.8)	*0.008*
Albumin (g/dL)	3.1 (2.0∼4,1)	2.6 (1.3∼3.8)	*0.001*
Calcium (mg/dL)	9.3 (7.9∼14.1)	9.3 (7.8∼14.5)	0.84
CRP (mg/dL)	0.50 (0.07~10.86)	0.85 (0.03∼19.85)	0.13
Creatinine (mg/dL)	1.0 (0.4∼10.9)	1.2 (0.5∼5.5)	0.53
Azotemia patients (n, %)	9 (33.3%)	10 (27.0%)	0.59
B2-MG (ug/mL)	4.4 (0.8∼29.8)	6.1 (2.1∼21.8)	0.80
LDH (IU/L)	195.0 (100∼771)	163.0 (79.0∼437.0)	*0.04*
Plasma cell in BM	30.8% (6.2∼96.2)	53.1% (1.2∼97.2)	*0.03*

Abbreviations; BJ protein, Bence-Jones protein; CRP, C-reactive protein; B2-MG, β₂-microglobulin; LDH, lactate dehydrogen ase; BM, bone marrow.

Table 3.

Univariate and multivariate analysis of clinicopathologic factors associated with overall survival

Factors (n)	2-year OS	Univariate P value	Multivariate
Factors (n)	2-year OS	Univariate P value	P value	Hazard ratio
Age
＞60 years (31) ≤60 years (33)	57.7% 77.0%	0.14	0.34	1.55 (0.63∼3.82)
Gender
Male (34) Female (30)	66.8% 68.4%	0.56	0.78	1.14 (0.46∼2.83)
ECOG (PS)
2/3 (18) 0/1 (46)	27.5% 80.1%	＜0.01	＜0.01	4.17 (1.68∼10.39)
ISS stage
Stage III (29) Stage I, II (35)	62.4% 71.4%	0.25	-	-
Urine electrophoresis
Whole Ig (37) FLC/undetectable (27)	57.7% 81.0%	0.15	0.13	2.12 (0.79∼5.67)
M-protein
＞3.7g/dL (32) ≤3.7g/dL (32)	66.9% 68.2%	0.74	-	-
Hb
＜8.0g/dL (22) ≥8.0g/dL (42)	63.7% 75.0%	0.59
Albumin
＜3.3g/dL (51) ≥3.3g/dL (13)	60.9% 92.3%	0.08
Calcium
＞10.0mg/dL (16) ≤10.0mg/dL (48)	55.6% 71.9%	0.08
C-reactive protein
＞0.5mg/dL (33) ≤0.5mg/dL (31)	57.1% 82.1%	0.02	0.03	3.02 (1.14∼7.99)
Creatinine
≥1.4mg/dL (22) ＜1.4mg/dL (42)	54.8% 73.3%	0.06
β₂-microglobulin
＞2.4ug/dL (58) ≤2.4ug/dL (6)	65.8% 83.3%	0.67
LDH
＞250IU/L (18) ≤250IU/L (46)	56.3% 75.0%	0.28
Plasma cells in BM
＞33% (38)	66.8%	0.86
≤33% (24)	70.2%

Abbreviations: FLC, free light-chain; See Table 1, 2.

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