Abstract 1893

Background:

Recent data has shown that the level of immunoglobulin free light chain (FLC) is a prognostic factor for patients with AL amyloidosis. Approximately 25% of patients with AL amyloidosis have coexistent multiple myeloma (MM) with myeloma-related end-organ damage and patients may also present with 310% plasma cells (PC) in the bone marrow (BM) in the absence of any MM features. The goal of this study was to determine the effect of increased BM plasmacytosis in the absence of MM end-organ damage on early mortality.

Methods:

We performed a retrospective study of 263 consecutive patients with AL amyloidosis seen at Mayo Clinic within 30 days of diagnosis from July 2002 – April 2009, to compare the effect of PC burden among those who died within 90 days of diagnosis (n=88) and those who survived more than 90 days after diagnosis (n=175). Only those patients with documented BM PC were included in this study. MM end-organ damage was defined according to the CRAB criteria.

Results:

In those who died <90 days after diagnosis and patients who lived beyond 90 days, the proportion of patients with 310% BM PC were 57% and 55%, respectively. Overall survival (OS) was significantly shorter in the early mortality group when there was 310% BM PC present at diagnosis (25 vs. 54 days, p=0.006), but this was not observed in the group who survived beyond 90 days (Figure 1). In patients with 310% BM PC, troponin-T, ejection fraction (EF), and hemoglobin (Hgb) were significantly worse in the early mortality cohort but patients who survived beyond 90 days had significant increase in intraventricular septal (IVS) thickness and beta-2 microglobulin (Table 1). As expected, patients with 310% BM PC in both cohorts had significantly higher serum M-spike and involved FLC (Table). The same cohort of patients were analyzed substituting MM-related end-organ damage for 310% BM PC and similar results were observed with the exception of uric acid and calcium being significantly higher in the early mortality cohort with MM (results not shown).

Conclusion:

This study demonstrated that an excess of early—but not late—deaths occur in AL amyloidosis patients with 310% BM PC at diagnosis. In our cohort, this finding can be attributed to higher troponin-T levels, indicating more severe cardiac involvement as observed by worse cardiac function. These findings warrant additional investigation.

Figure 1
Figure 1. Kaplan-Meier analysis of AL amyloidosis patients who died within 90 days of diagnosis, demonstrating shorter overall survival in patients with 310% BM PC (p=0.006)
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Kaplan-Meier analysis of AL amyloidosis patients who died within 90 days of diagnosis, demonstrating shorter overall survival in patients with 310% BM PC (p=0.006)

Figure 1
Figure 1. Kaplan-Meier analysis of AL amyloidosis patients who died within 90 days of diagnosis, demonstrating shorter overall survival in patients with 310% BM PC (p=0.006)
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Kaplan-Meier analysis of AL amyloidosis patients who died within 90 days of diagnosis, demonstrating shorter overall survival in patients with 310% BM PC (p=0.006)

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Table 1:

Variables (median) analyzed in patients who died within 90 days or survived beyond 90 days of diagnosis of AL amyloidosis based on their BM PC%

VariableDied within 90 days of diagnosisSurvived beyond 90 days of diagnosis
BM PC <10% (n = 38)BM PC 310% (n = 50)p-valueBM PC <10% (n = 79)BM PC 310% (n = 96)p-value
Hemoglobin, g/dl 13.6 12.6 0.01 13.4 13.1 0.55 
Serum M-spike, g/dl 0 0 0.02 0.5 1.2 0.04 
Beta-2 microglobulin, mcg/ml 3.4 4.6 0.17 2.61 3.16 0.01 
Troponin-T, ng/ml 0.07 0.14 0.01 0.01 0.01 0.30 
NT-proBNP, pg/ml 5644 9360 0.09 1325 1261 0.46 
EF, % 55.5 45 0.02 64 64 0.74 
IVS, mm 14 15 0.21 12 13.5 0.01 
PCLI, % 0 0.2 0.17 0 0.1 0.001 
BM PC, % 5 20 <0.0001 5 16.5 <0.0001 
Involved FLC, mg/dl 23.2 86.9 <0.0001 13.5 31.1 0.0004 
Lambda- restricted patients, % 34.1 37.5 0.94 31.0 37.4 0.56 
VariableDied within 90 days of diagnosisSurvived beyond 90 days of diagnosis
BM PC <10% (n = 38)BM PC 310% (n = 50)p-valueBM PC <10% (n = 79)BM PC 310% (n = 96)p-value
Hemoglobin, g/dl 13.6 12.6 0.01 13.4 13.1 0.55 
Serum M-spike, g/dl 0 0 0.02 0.5 1.2 0.04 
Beta-2 microglobulin, mcg/ml 3.4 4.6 0.17 2.61 3.16 0.01 
Troponin-T, ng/ml 0.07 0.14 0.01 0.01 0.01 0.30 
NT-proBNP, pg/ml 5644 9360 0.09 1325 1261 0.46 
EF, % 55.5 45 0.02 64 64 0.74 
IVS, mm 14 15 0.21 12 13.5 0.01 
PCLI, % 0 0.2 0.17 0 0.1 0.001 
BM PC, % 5 20 <0.0001 5 16.5 <0.0001 
Involved FLC, mg/dl 23.2 86.9 <0.0001 13.5 31.1 0.0004 
Lambda- restricted patients, % 34.1 37.5 0.94 31.0 37.4 0.56 
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Disclosures:

Lacy:Celgene: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria.

Topics:
immunoglobulin deposition disease, plasma cells, plasmacytosis, primary amyloidosis, end organ damage, free immunoglobulin light chain, hemoglobin, beta 2-microglobulin, m-spike, multiple myeloma

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2010 by The American Society of Hematology
2010
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