scholarly journals Quantification of number of CD38 sites on bone marrow plasma cells in patients with light chain amyloidosis and smoldering multiple myeloma

2018 ◽  
Vol 94 (5) ◽  
pp. 767-776 ◽  
Author(s):  
Katharina Kriegsmann ◽  
Tobias Dittrich ◽  
Brigitte Neuber ◽  
Mohamed H. S. Awwad ◽  
Ute Hegenbart ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Light Chain Amyloidosis ◽  
Smoldering Multiple Myeloma ◽  
Bone Marrow Plasma

Immunoglobulin Free Light Chain Ratio Is an Independent Risk Factor for Progression of Smoldering Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1487-1487 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
Dirk Larson ◽  
Joanne Benson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Free Light Chain ◽  
M Protein ◽  
Baseline Serum ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Bone Marrow Plasma

Abstract Background: Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell proliferative disorder with a high risk of progression to symptomatic multiple myeloma. Identification of risk factors that predict progression of SMM to symptomatic MM could identify higher risk patients who might benefit from chemoprevention or more intensive surveillance. We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased the risk of progression to active myeloma. Methods: Of 276 pathologically confirmed SMM patients seen at the Mayo Clinic from 1970 to 1995, baseline serum samples obtained within 30 days of diagnosis were available in 273. Results: At a median follow-up of surviving patients of 12.4 years, transformation to active disease has occurred in 161 (59%) patients. An abnormal FLC ratio was present at baseline in 90% of patients. The best break-point for predicting risk of progression was a FLC ratio less than or equal to 0.125 or greater than or equal to 8 (hazard ratio, 2.3; 95% CI, 1.6–3.2) [Figure 1]. The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of plasma cells in the bone marrow and size of serum M-proteins (bone marrow plasma cells ≥ 10% and serum M protein ≥ 3 g/dL; bone marrow plasma cells ≥ 10% but serum M protein < 3 g/dL; and serum M protein ≥ 3 g/dL but bone marrow plasma cells < 10%). Incorporating the FLC ratio into the risk model, the division of patients into high-, intermediate-, and low-risk groups is 28, 42, and 30% with 5 year progression rates of 76, 51, and 25%, respectively [Figure 2]. Conclusions: The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM. Figure Figure Figure Figure

Serum Free Light Chain Ratio in Distinguishing Smoldering Multiple Myeloma From Active Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3948-3948
Author(s):  
Jeremy T Larsen ◽  
Shaji Kumar ◽  
S. Vincent Rajkumar
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Predictive Value ◽  
Plasma Cells ◽  
Organ Damage ◽  
End Organ Damage ◽  
Cut Point ◽  
Smoldering Multiple Myeloma ◽  
Bone Marrow Plasma

Abstract Abstract 3948 Background: Smoldering multiple myeloma (SMM) is an asymptomatic precursor disease of multiple myeloma, and is defined by excess bone marrow plasma cells and monoclonal protein without evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions [CRAB]). The identification of SMM patients with more aggressive underlying disease remains a challenge. We hypothesize that SMM is a clinical entity comprised of both premalignant, high-risk MGUS and early multiple myeloma in transition to malignant disease, which may be differentiated with the use of the serum FLC (FLC) ratio. Methods: This was a retrospective analysis of 586 patients with newly diagnosed SMM from 1970–2010 with available stored serum samples around the time of diagnosis to be utilized for quantification of FLC ratios. SMM was defined by the International Myeloma Working Group 2003 definition; serum M-protein ≥ 3 g/dL and/or ≥ 10% bone marrow plasma cells with no evidence of CRAB features. The immunoglobulin FLC assay (Binding Site, U.K.) was used for testing. The FLC ratio was calculated as κ/λ (reference range 0.26–1.65). The involved/uninvolved FLC ratio was recorded to simplify the reporting of data. Receiver Operating Characteristics (ROC) curves were created to assess the ability of the FLC ratio to discriminate patients who progressed to symptomatic multiple myeloma (MM) in the first 2 years or at any point during follow-up versus patients without evidence of progression. Patients with less than 24 months follow-up without progression were censored. The optimal diagnostic cut-point for FLC involved/uninvolved ratio to identify patients with progressive disease from the ROC curve was >88.6 (equivalent to <0.011 or >88.6). For ease of clinical application, the optimal value for involved/uninvolved FLC ratio was rounded to >100. Time to progression (TTP) from date of the initial FLC to active MM was calculated using Kaplan-Meier analysis and compared to patients with a high (>100) and low (<100) involved/uninvolved FLC ratio at time of SMM diagnosis. TTP within 24 months of the initial FLC was also calculated. Results: During the study period, 54% of patients progressed to active MM. On ROC analysis, a cut-point of >100 corresponded to a sensitivity of 25% (95% CI, 20.5–30.4) and specificity of 99.3% (97.3–99.9), with positive likelihood (+LR) ratio of 33.9 (38.1–41.0), negative likelihood ratio (−LR) of 0.75 (0.2–3.0), positive predictive value (PPV) of 97.6 (91.5–99.7) and negative predictive value of 53.0 (48.5–57.4). Using the ROC to assess progression to MM within 24 months (Figure 1), sensitivity was 29.6% (23.5–36.4), specificity 94.5% (91.7–96.5), +LR 5.36 (4.3–6.6), -LR 0.75 (0.5–1.1), PPV 85.8 (77.7–91.8), and NPV 54.3 (49.8–58.9). Median TTP to active MM in the FLC >100 group was 15 months (9–17) versus 52 months (44–60) in the FLC <100 group (p <.0001) [Figure 2]. In the FLC ratio >100 group, progression at 1 year was 47%, 76% at 2 years, and 90% at 3 years. Only 25% of the FLC <100 patients had progressed at 2 years. The most common progression event was bone disease (42%), followed by anemia (26%), renal impairment (23%), and hypercalcemia (5%). Conclusion: Elevation of the FLC ratio >100 (or <0.01) is highly specific for the future development of active MM, with 76% of these patients developing end-organ damage requiring therapy within 2 years. Risk of transformation to MM in the FLC <100 group was similar to previously reported rates of 10% per year for the first 5 years. Development of an FLC ratio >100 is associated with increasing disease burden and in this study behaved in a malignant fashion rather than a precursor state. The FLC is a simple and useful predictor of progression to MM in SMM, and patients with FLC ratios of <0.01 or >100 within the first 2 years of SMM diagnosis should be monitored especially closely. Future studies are needed to determine optimum cutoffs for FLC ratio to where a change in definition of MM could be considered. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Bence Jones Proteinuria in Smoldering Multiple Myeloma As Predictor Marker of Progression to Symptomatic Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3369-3369 ◽  
Author(s):  
Veronica Gonzalez de la Calle ◽  
Ramon Garcia-Sanz ◽  
Eduardo Sobejano ◽  
Enrique M. Ocio ◽  
Noemi Puig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Symptomatic Disease ◽  
Risk Of Progression ◽  
Bone Marrow Plasma ◽  
Active Disease ◽  
Bence Jones Proteinuria

Abstract BACKGROUND Smoldering multiple myeloma (SMM) is a plasma cell proliferative disorder with no related organ or tissue impairment. It is associated with a risk of progression to symptomatic multiple myeloma (MM) of approximately 10% per year. Several prognostic factors for the progression to active disease have been identified, such as those defined by the Mayo Clinic including the proportion of bone marrow plasma cells, the serum monoclonal protein level at diagnosis and the serum immunoglobulin free light chain ratio (FLC); or those defined by the Spanish Group including the proportion of bone marrow aberrant plasma cells assessed by flow cytometry plus immunoparesis. The presence of Bence Jones (BJ) proteinuria is a myeloma feature associated with renal function and tumor burden as well. There is lack of evidence about the role of BJ proteinuria in SMM as predictor marker of progression to symptomatic disease. AIMS The goal of the present study was to investigate the role of the presence of Bence Jones proteinuria at diagnosis in SMM as predictor of progression to symptomatic disease. METHODS We reviewed 147 medical records of SMM patients from area of Castilla y León (Spain), diagnosed between 1983 and 2013, according to the criteria of the International Myeloma Working Group. The primary endpoint was time to progression to active multiple myeloma (hypercalcemia, renal insufficiency, anemia or bone lesions). RESULTS 147 patients with SMM were included in the analysis. The median age at diagnosis was 69 years-old (range: 34-90).The serum M-protein at diagnosis ranged from 1 to 26 g/l (median,25). 70% of SMM were Ig G subtype. The proportion of bone marrow plasma cells ranged from 1% to 55% (median, 14). In 64 % of SMM, the percentage of aberrant plasma cells assessed by flow cytometry was superior to 95% and 51% had immunoparesis. Bence Jones proteinuria was detected at diagnosis in 40 patients (27%) and the average amount of urinary monoclonal light chain was 236 mg per 24h. Of those patients, 58% had a monoclonal kappa light chain. The FLC ratio was assessed in 18 patients and it was abnormal (<0.26 or >1.65) in 83% of them. The median level of involved Immunoglobulin was 88.5 mg/l (range, 13-1200) and the median ratio of involved to uninvolved was 10.8 (range, 2.2-3360). In 4 patients, FLC ratio was greater than 100. At a median follow-up of 54 months, progression to active disease occurred in 49%. Anemia was the most common CRAB feature at the time of progression. Median time to progression (TTP) to symptomatic disease in the whole series was 63 months. SMM with BJ proteinuria had a significantly shorter median TTP to active disease as compared with patients without BJ proteinuria (21.7 months vs 82.9 months ;HR: 2.44, IC 95%: 1.48-4.02; p<0.001). The progression risk at 2 years in the BJ group of SMM was 53%. Multivariate analysis selected BJ proteinuria at diagnosis as an independent variable for progression to symptomatic MM (HR: 2.47, IC 95%: 1.32-4.63; P=0.005). Using this independent variable, we identified 4 risk categories according to amount of urinary monoclonal light chain: 0 mg per 24h; 1-250 mg/24h; 251-500 mg/24h ; or more than 500 mg/24h, with a median TTP of 83, 37, 16 and 7 months, respectively; p <0.001. CONCLUSIONS The presence of Bence Jones proteinuria at diagnosis in SMM patients is associated with significantly higher risk of progression to active MM (53% risk of progression at 2 years). Moreover, the presence of more than 500 mg of BJ proteinuria can be considered as a marker for the identification of ultra high risk SMM. Disclosures No relevant conflicts of interest to declare.

The Natural History of Smoldering (Asymptomatic) Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3396-3396 ◽  
Author(s):  
Robert Kyle ◽  
Ellen Remstein ◽  
Terry Therneau ◽  
Angela Dispenzieri ◽  
Paul Kurtin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
M Protein ◽  
Cell Content ◽  
Bone Marrow Plasma ◽  
M Spike

Abstract Smoldering multiple myeloma (SMM) is characterized by a serum M protein ≥ 3g/dL and/or 10% or more of plasma cells in the bone marrow. However, the definition is not standardized, and it is not known whether both serum M protein levels and bone marrow plasma cell counts are necessary for diagnosis or if one parameter is sufficient. We reviewed the medical records and bone marrows of all patients from Mayo Clinic seen within 30 days of recognition of an IgG or IgA M protein ≥ 3g/dL or a bone marrow containing ≥ 10% plasma cells from 1970 to 1995. This allows for a minimum potential follow-up of 10 years. Patients with end-organ damage at baseline from plasma cell proliferation, including active multiple myeloma (MM) and primary amyloidosis (AL) and those who had received chemotherapy were excluded. A differential of the bone marrow aspirate coupled with the bone marrow biopsy morphology and immunohistochemistry using antibodies directed against CD138, MUM-1 and Cyclin D1 were evaluated in every case in order to estimate the plasma cell content. In all, 301 patients fulfilled either of the criteria for SMM. Their median age was 64 years and only 3% were less than 40 years of age; 60% were male. The median hemoglobin value was 12.9 g/dL; 7% were less than 10 g/dL, but the anemia was unrelated to plasma cell proliferation. IgG accounted for 75%, IgA 22%, and biclonal proteins were found in 3%. The serum light-chain was κ in 67% and λ in 33%. The median serum M spike was 2.9 g/dL; 11% were at least 4.0 g/dL. Uninvolved serum immunoglobulins were reduced in 81%; only 1 immunoglobulin was reduced in 31% and both were decreased in 50%. The urine contained a monoclonal κ protein in 36% and λ in 18% and 46% were negative. The median size of the urine M spike was 0.04 g/24h; only 5 (3%) were &gt; 1 g/24h. The median bone marrow plasma cell content was 15 – 19%; 10% had less than 10% plasma cells, while 10% had at least 50% plasma cells in the bone marrow. Cyclin D-1 was expressed in 17%. Patients were categorized into 3 groups: Group 1, serum M protein ≥ 3g/dL and bone marrow containing ≥ 10% plasma cells (n= 113, 38%); Group 2, bone marrow plasma cells ≥ 10% but serum M protein &lt; 3g/dL (n= 158, 52%); Group 3, serum M protein ≥ 3g/dL but bone marrow plasma cells &lt; 10% (n= 30, 10%). During 2,204 cumulative years of follow-up 85% died (median follow-up of those still living 10.8 years), 155 (51%) developed MM, while 7 (2%) developed AL. The overall rate of progression at 10 years was 62%; median time to progression was 5.5 yrs. The median time to progression was 2.4, 9.2, and 19 years in groups 1, 2, and 3 respectively; correspondingly at 10 years, progression occurred in 76%, 59%, and 32% respectively. Significant risk factors for progression with univariate analysis were serum M spike ≥ 4g/dL (p &lt; 0.001), presence of IgA (p = 0.003), presence of urine light chain (p = 0.006), presence of λ urinary light chain (p = 0.002), bone marrow plasma cells ≥ 20% (p &lt; 0.001) and reduction of uninvolved immunoglobulins (p &lt; 0.001). The hemoglobin value, gender, serum albumin, and expression of cyclin D-1 were not of prognostic importance. On multivariate analysis, the percentage of bone marrow plasma cells was the only significant factor predicting progression to MM or AL.

Assessing Proteostasis and Proteasome Stress In Light Chain Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3992-3992 ◽  
Author(s):  
Laura Oliva ◽  
Giovanni Palladini ◽  
Fulvia Cerruti ◽  
Niccolò Pengo ◽  
Paolo Cascio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
Ex Vivo ◽  
Response To Therapy ◽  
Proteasome Activity ◽  
Peptidase Activity ◽  
Light Chain Amyloidosis ◽  
Bone Marrow Plasma

Abstract Abstract 3992 Recently, proteasome inhibitors (PI) proved powerful against multiple myeloma (MM), the neoplastic transformation of plasma cells. The balance between proteasome expression and degradative workload (mainly contributed by protein synthesis) proved a crucial determinant of apoptotic sensitivity of MM cells to proteasome inhibition (Bianchi et al, Blood 2009). Light chain amyloidosis (AL) is a plasma cell dyscrasia caused by a bone marrow plasma cell clone synthesizing structurally unstable, misfolded, monoclonal immunoglobulin (Ig) light chains, which polymerize into amyloid fibrils. Interestingly, AL is proving even more sensitive than MM to PI in clinical trials with unprecedented response rates (>80%) rapidly achieved in previously untreated patients (Kastritis et al, J Clin Oncol 2010), raising the question as to whether, and if so why, AL cells are intrinsically more sensitive than MM to PI. We hypothesized that AL cells suffer from intense proteasome stress linked to the synthesis of the misfolded Ig light chain, thereby facing constitutive proteotoxicity. To test this hypothesis, we set out to optimize purification of primary bone marrow plasma cells from AL patients, and determine: intrinsic sensitivity to the PI bortezomib (by FACS); proteasome activity (by fluorogenic assays); accumulation of ubiquitinated (Ub) proteins and Ig light chain (by immunofluorescence). Our ex vivo studies demonstrated twofold higher PI sensitivity in AL plasma cells as compared to primary MM cells (EC50 in 24 hr apoptosis assays: AL, 8.3 ± 2.2 nM; MM, 15.1 ± 3.0 nM). We also found that, similar to MM cells, proteasome activity of primary AL plasma cells varies greatly among different patients (5.2 ± 3.6 nM substrate specifically cleaved by the chymotryptic β-peptidase activity per cell per min). Furthermore, accumulation of Ub proteins strongly correlates with light chain content, suggesting a crucial role for paraprotein synthesis and/or retention on proteasome stress. Interestingly, unlike MM cells, we failed to detect a clear correlation between proteasome activity and ex vivo assessed PI sensitivity, possibly due to intracellular toxicity of the misfolded light chain. The resulting hypothesis that different mutations could result in different intrinsic proteotoxicity in AL cells is currently being tested. In conclusion, our integrated approach indicates that AL cells are intrinsically more sensitive to PI than MM cells, providing a potential explanation for the excellent clinical responses. Moreover, we established a technological platform to investigate proteostasis and proteotoxic stress in primary AL cells. This strategy may help investigate the efficacy of proteostasis regulators on plasma cell dyscrasias, including MM, and identify molecular markers of clinical use to predict disease severity and response to therapy. Disclosures: No relevant conflicts of interest to declare.

The clinical utility and prognostic value of multiparameter flow cytometry immunophenotyping in light-chain amyloidosis

Blood ◽  
2011 ◽  
Vol 117 (13) ◽  
pp. 3613-3616 ◽  
Author(s):  
Bruno Paiva ◽  
María-Belén Vídriales ◽  
José J. Pérez ◽  
María-Consuelo López-Berges ◽  
Ramón García-Sanz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Light Chain ◽  
Clinical Utility ◽  
Plasma Cells ◽  
Multiparameter Flow Cytometry ◽  
Significant Prognostic Factor ◽  
Clinical Value ◽  
Light Chain Amyloidosis ◽  
Bone Marrow Plasma

Abstract The clinical value of multiparameter flow cytometry (MFC) immunophenotyping in primary or light chain amyloidosis (AL) remains unknown. We studied 44 consecutive bone marrow samples from newly diagnosed patients with amyloidosis; 35 patients with AL and 9 with other forms of amyloidosis. Monoclonal plasma cells (PCs) were identifiable by MFC immunophenotyping in 34 of 35 (97%) patients with AL, whereas it was absent from all but 1 of the 9 (11%) patients with other forms of amyloidosis. Quantification of bone marrow plasma cells (BMPCs) by MFC immunophenotyping was a significant prognostic factor for overall survival (OS) (≤ 1% vs > 1% BMPC cutoff; 2-year OS rates of 90% vs 44%, P = .02). Moreover, detecting persistent normal PCs at diagnosis identifies a subgroup of patients with AL with prolonged OS (> 5% vs ≤ 5% normal PC within all BMPC cutoff, 2-year rates of 88% vs 37%, P = .01). MFC immunophenotyping could be clinically useful for the demonstration of PC clonality in AL and for the prognostication of patients with AL.

A Highly Heterogeneous Mutational Pattern in POEMS Syndrome

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-19
Author(s):  
Jia Chen ◽  
Xue-min Gao ◽  
Hao Zhao ◽  
Hao Cai ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Poems Syndrome ◽  
Newly Diagnosed ◽  
Driver Genes ◽  
Target Region ◽  
Whole Exome ◽  
Bone Marrow Plasma

Background: POEMS syndrome is a rare plasma cell dyscrasia. Despite the presence of monoclonal protein, POEMS syndrome patients commonly have less than 5% monoclonal plasma cells in the bone marrow. Only one study has reported the genetic and transcriptional features of bone marrow plasma cells, and the underlying role of aberrant plasma cells is not well understood. Herein, in the current study, we aimed to characterize the genetic profile of bone marrow CD138-positive cells from Chinese patients with newly diagnosed POEMS syndrome. Methods: Forty-two patients with newly diagnosed POEMS syndrome based on the International Myeloma Working Group criteria at our institute were included in our study. Twenty milliliters of bone marrow aspirates was obtained and sorted by magnetic microbeads conjugated to monoclonal human anti-CD138 antibodies. The mutational features of these bone marrow plasma cells were analyzed using a two-step strategy. DNA of the bone marrow plasma cells from ten patients was first sequenced by whole exome sequencing to find significantly mutated genes and mutated driver genes, with paired peripheral blood mononuclear cells as a control. Bone marrow plasma cells of an additional thirty-two patients were then analyzed by target region sequencing to validate the mutations. Results: Whole exome sequencing of 10 newly diagnosed patients showed a total of 170 somatic mutations in exonic regions and splicing sites. Three significantly mutated genes-LILRB1 (10%), HEATR9 (20%), and FMNL2 (10%)-and eight mutated known driver genes (MYD88, NFKB2, CHD4, SH2B3, POLE, STAT3, CHD3, CUX1) were identified in five patients. The mutation spectrum of WES revealed C &gt; T/G &gt; A as the most common mutation type, while the mutation signature was not the same as known signatures reported in various cancer types. For significant pathway and gene ontology analysis, 69 genes with possibly pathogenic nonsynonymous mutations were selected. Mutated genes were enriched in pathways including "chromatin organization", "chromatin modifying enzymes", and "apoptosis", and terms such as "cellular anatomical entity", "regulatory region nucleic acid binding" and "centrosome" that are used to describe cellular structure construction. To evaluate the mutation prevalence of genes identified in WES, we performed target region sequencing of 77 candidate genes in 32 other patients. The candidate gene list consisted of significantly mutated genes and known driver genes identified in WES, recurrently mutated genes previously detected in POEMS syndrome, the VEGF gene, and genes of light-chain amyloidosis, multiple myeloma, hematopoietic disease or lymphoid neoplasm in the public databases. As a result, a total of 32 mutated genes were identified in 28 of 32 patients. Genes recurrently mutated in more than three patients included CUX1 (19%), DNAH5 (16%), USH2A (16%), KMT2D (16%), and RYR1 (12%). Driver genes of multiple myeloma (BIRC3, LRP1B, KDM6A, ATM) and eleven genes reported in light-chain amyloidosis were also identified in target region sequencing. Notably, VEGFA mutations were detected in one patient. Conclusions: Heterogeneous genomic profiles of bone marrow plasma cells in POEMS syndrome were revealed in our study. The mutational landscape of POEMS syndrome might share some similarity to that of other plasma cell diseases. Disclosures No relevant conflicts of interest to declare.

scholarly journals Coexistent Multiple Myeloma or Increased Bone Marrow Plasma Cells Define Equally High-Risk Populations in Patients With Immunoglobulin Light Chain Amyloidosis

2013 ◽  
Vol 31 (34) ◽  
pp. 4319-4324 ◽  
Author(s):  
Taxiarchis V. Kourelis ◽  
Shaji K. Kumar ◽  
Morie A. Gertz ◽  
Martha Q. Lacy ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
Survival Rates ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Characteristic Analysis ◽  
Bone Marrow Plasma

Purpose There is consensus that patients with light chain (AL) amyloidosis with hypercalcemia, renal failure, anemia, and lytic bone lesions attributable to clonal expansion of plasma cells (CRAB criteria) also have multiple myeloma (MM). The aim of this study was to examine the spectrum of immunoglobulin AL amyloidosis with and without MM, with a goal of defining the optimal bone marrow plasma cell (BMPC) number to qualify as AL amyloidosis with MM. Patients and Methods We identified 1,255 patients with AL amyloidosis seen within 90 days of diagnosis between January 1, 2000, and December 31, 2010. We defined a population of patients with coexisting MM on the basis of the existence of CRAB criteria (AL-CRAB). Receiver operating characteristic analysis determined the optimal BMPC cut point to predict for 1-year mortality in patients with AL amyloidosis without CRAB to produce two additional groups: AL only (≤ 10% BMPCs) and AL plasma cell MM (AL-PCMM; > 10% BMPCs). Results Among the 1,255 patients, 100 (8%) had AL-CRAB, 476 (38%) had AL-PCMM, and 679 (54%) had AL only. Their respective median overall survival rates were 10.6, 16.2, and 46 months (P < .001). Because the outcomes of AL-CRAB and AL-PCMM were similar, they were pooled for univariate and multivariate analyses. On multivariate analysis, pooled AL-CRAB and AL-PCMM retained negative prognostic value independent of age, Mayo Clinic AL amyloidosis stage, prior autologous stem-cell transplantation, and difference between the involved and uninvolved free light chain. Conclusion Patients with AL amyloidosis who have more than 10% BMPCs have a poor prognosis, similar to that of patients with AL-CRAB, and should therefore be considered together as AL amyloidosis with MM.

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