scholarly journals Multiple myeloma with intramedullary masses of M-component

Blood ◽  
1975 ◽  
Vol 46 (6) ◽  
pp. 931-935
Author(s):  
GM Bernier ◽  
VD Duca Jr ◽  
R Brereton ◽  
RC Graham Jr
Keyword(s):  
Electron Microscopy ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Fluorescent Antibody ◽  
Intracytoplasmic Inclusions

The bone marrow of a patient with light chain myeloma and amyloidosis was substantially infiltrated with basophilic globular particles. The globules, which were confined to the bone marrow, ranged in size from tiny intracytoplasmic inclusions to large (100 mu) extracellular particles. Both the intra- and extracellular globules stained with fluorescent antibody directed against the light chain (kappa) produced by the patient's abnormal clone, and not with other fluorescent antiserums. By electron microscopy, even the largest extracytophasmic globules were bounded at least in part by rough membranes, suggesting that their extreme size was the result of cellular synthesis rather than extracellular coalescence.

scholarly journals Multiple myeloma with intramedullary masses of M-component

Blood ◽  
1975 ◽  
Vol 46 (6) ◽  
pp. 931-935 ◽  
Author(s):  
GM Bernier ◽  
VD Duca Jr ◽  
R Brereton ◽  
RC Graham Jr
Keyword(s):  
Electron Microscopy ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Fluorescent Antibody ◽  
Intracytoplasmic Inclusions

Abstract The bone marrow of a patient with light chain myeloma and amyloidosis was substantially infiltrated with basophilic globular particles. The globules, which were confined to the bone marrow, ranged in size from tiny intracytoplasmic inclusions to large (100 mu) extracellular particles. Both the intra- and extracellular globules stained with fluorescent antibody directed against the light chain (kappa) produced by the patient's abnormal clone, and not with other fluorescent antiserums. By electron microscopy, even the largest extracytophasmic globules were bounded at least in part by rough membranes, suggesting that their extreme size was the result of cellular synthesis rather than extracellular coalescence.

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.

scholarly journals Successful Treatment of Concurrently Diagnosed Multiple Myeloma and Myelodysplastic Syndrome with Isolated Del(5q) with Lenalidomide, Bortezomib, and Dexamethasone

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Nyomi Washington ◽  
Eugen A Shippey ◽  
Michael B Osswald
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Partial Response ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Biopsy ◽  
Induction Therapy ◽  
Successful Treatment ◽  
Light Chain ◽  
Plasma Cells ◽  
Bone Marrow Blasts

Lenalidomide is known to be an effective therapy for multiple myeloma (MM) and for myelodysplastic syndrome with isolated del(5q). However, there have been very few reports of treatment of both conditions using lenalidomide when they are diagnosed concurrently. A review of the literature revealed two reports of MM and del(5q) MDS treated with lenalidomide. We report the case of a patient simultaneously diagnosed with multiple myeloma and myelodysplastic syndrome with isolated del(5q) who was treated successfully with lenalidomide. The patient is a 74 year old female who was referred to hematology for worsening chronic macrocytic anemia with a hemoglobin of 9.4 g/dL. A serum protein electrophoresis (SPEP) was obtained during her workup and demonstrated an IgG kappa monoclonal spike of 4.7 g/dL. Free light chain analysis demonstrated a kappa/lambda ratio of 36.7. The patient was mildly hypercalcemic at 10.6 g/dL but had no renal insufficiency. Platelet and white blood cell counts were normal. There were no osteolytic lesions on skeletal survey and a whole body PET scan identified no bony disease or plasmacytomas. A β-2 microglobulin level was 3.7 mg/L and albumin was 3.3 g/dL. Bone marrow biopsy revealed 60% plasma cells in a 70% cellular marrow. Granulocytic and megakaryocytic dysplasia was identified. Fluorescence in situ hybridization returned showing a 4:14 translocation in 72% of analyzed nuclei and monosomy 13 in 61% of nuclei analyzed consistent with an unfavorable risk profile. Chromosome analysis also revealed a 5q deletion in 15 of 20 analyzed cells. Bone marrow blasts were measured at 1%. Therefore, the patient concurrently met diagnostic criteria for stage II IgG kappa multiple myeloma per the International Staging System and low risk myelodysplastic syndrome with isolated del(5q) per the 2016 WHO classification of MDS with a Revised International Prognostic Scoring System Score (IPSS-R) of 2. She was started on lenalidomide 25 mg daily, bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 and dexamethasone 20 mg on days 1, 8, and 15 of a 21 day cycle. After 3 cycles of therapy, serum immunofixation electrophoresis showed an unquantifiably low IgG kappa monoclonal spike and the patient's kappa/gamma light chain ratio had normalized to 1.1. Hemoglobin and calcium returned to normal. On repeat bone marrow biopsy, there was normocellular marrow with 4% polytypic plasma cells by kappa/lambda immunohistochemistry. No dysplasia was identified and bone marrow blasts were 1.5%. Therefore, the patient achieved a very good partial response (VGPR) to therapy for multiple myeloma according to International Myeloma Working Group criteria within 3 months. She met National Comprehensive Cancer Network criteria for response of her MDS to lenalidomide by normalization of hemoglobin. The patient's case demonstrates successful treatment of concurrently diagnosed multiple myeloma and MDS with isolated del(5q) using lenalidomide. Among the two other similar cases we discovered in the literature, one patient was treated with low-dose lenalidomide and dexamethasone [Nolte, et al. Eur J Haematol. 2017 Mar;98(3):302-310.], and the other patient was treated with high-dose lenalidomide and dexamethasone, achieving a partial response [Ortega, et al. Leuk Res. 2013 Oct;37(10):1248-50.]. Neither patient received a proteasome inhibitor. In our case, the patient was treated with higher intensity induction therapy for multiple myeloma and achieved a VGPR. She did not have worsening cytopenias during therapy, and in fact experienced normalization of her blood counts. Therefore, it is reasonable to treat patients simultaneously diagnosed with MM and MDS with isolated del(5q) with standard three-drug induction therapy for multiple myeloma. While our approach makes sense in the abstract, hematology/oncologists should be aware that it works in practice. Disclosures No relevant conflicts of interest to declare.

scholarly journals Immunoglobulin gene rearrangement in Koreans with multiple myeloma: Clonality assessment and repertoire analysis using next-generation sequencing

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253541
Author(s):  
Miyoung Kim ◽  
Kibum Jeon ◽  
Kasey Hutt ◽  
Alyssa M. Zlotnicki ◽  
Hyo Jung Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Next Generation Sequencing ◽  
Light Chain ◽  
Gene Rearrangement ◽  
Lymphoid Cells ◽  
Immunoglobulin Gene ◽  
Next Generation ◽  
Korean Patients ◽  
Generation Sequencing

Introduction We assessed the applicability of next-generation sequencing (NGS)-based IGH/IGK clonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time. Methods Fifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted the IGH and IGK genes was performed using IGH FR1 and IGK primer sets. Results Clonal IGH and IGK rearrangements were observed in 74.2% and 67.7% of samples from Korean patients with kappa-restricted MM, respectively (90.3% had one or both), and in 60.7% and 95.5% of samples from those with lambda-restricted MM, respectively (85.7% had one or both). In total, 88.1% of samples from Koreans with MM had clonal IGH and/or IGK rearrangement. Clonal rearrangement was not significantly associated with the bone marrow plasma cells as a proportion of all BM lymphoid cells. IGHV3-9 (11.63%) and IGHV4-31 (9.30%) were the most frequently reported IGHV genes and were more common in Koreans with MM than in Western counterparts. IGHD3-10 and IGHD3-3 (13.95% each) were the most frequent IGHD genes; IGHD3-3 was more common in Koreans with MM. No IGK rearrangement was particularly prevalent, but single IGKV-J rearrangements were less common in Koreans with kappa-restricted MM than in Western counterparts. IGKV4-1 was less frequent in Koreans regardless of light chain type. Otherwise, the usages of the IGH V, D, and J genes and of the IGK gene were like those observed in previous Western studies. Conclusion NGS-based IGH/IGK clonality testing ought to be applicable to most Koreans with MM. The overrepresentation of IGHV3-9, IGHV4-31, and IGHD3-3 along with the underrepresentation of IGKV4-1 and the differences in IGK gene rearrangement types suggest the existence of ethnicity-specific variations in this disease.

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.

Superior Rate of Complete Response with up-Front Velcade-Thalidomide-Dexamethasone Versus Thalidomide-Dexamethasone in Newly Diagnosed Multiple Myeloma Is Not Affected by Adverse Prognostic Factors, Including High-Risk Cytogenetic Abnormalities.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1662-1662
Author(s):  
Michele Cavo ◽  
Nicoletta Testoni ◽  
Carolina Terragna ◽  
Giulia Marzocchi ◽  
Sandra Durante ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Light Chain ◽  
Complete Response ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Cox Regression Analysis

Abstract Complete response (CR) is an important objective of autologous stem-cell transplantation (ASCT) in multiple myeloma (MM). In comparison with conventional induction treatments, newer combinations of novel agents may effect increased rates of CR and near CR (nCR), a benefit potentially translating into even higher frequencies of CR/nCR after ASCT and improved clinical outcome. We designed a phase III study to detect an increase in CR+nCR rates from 10–15% with conventional Thalidomide-Dexamethasone (TD) to 20–30% with Velcade added to TD (VTD) in newly diagnosed MM. Both TD and VTD were given as three 21-day cycles in preparation for double ASCT. In the present analysis, CR+nCR rates by the two induction treatments were examined in relationship to baseline prognostic variables in 399 evaluable pts aged ≤65 years, of whom 199 randomized to VTD and 200 to TD. All analyses were intent to treat. In comparison with TD, VTD effected higher rates of CR+nCR (12% vs 33%, P&lt;0.001) and of ≥very good partial response (VGPR) (30% vs 61%, P&lt;0.001). By univariate analysis, superiority of VTD to TD was maintained across all sub-group analyses according to standard prognostic factors, including β2-m, albumin, stage (ISS), Hb, PLTs, bone marrow PC, M protein isotype, LDH, CRP. In particular, the rates of CR+nCR with VTD vs TD in pts with standard poor prognostic factors were as follows: ISS stage 3 (23.5% vs 6%, P=0.03), Hb&lt;10 g/dL (24% vs 4%, P=0.002), PLTs&lt;150.000/μL (35% vs 4%, P=0.009), bone marrow PC ≥50% (31% vs 13%, P&lt;0.001), IgA isotype (63% vs 15%, P&lt;0.001), LDH &gt;190 U/L (33% vs 9%, P&lt;0.001), CRP ≥8 mg/L (29% vs 10%, P=0.004). We next examined CR+nCRs by treatment arms in relationship to cytogenetics (FISH data available in 93% to 99% of all pts). Superior CR+nCR rates were effected by VTD vs TD in the presence of high-risk cytogenetics, including del(13) (39% vs 10%, P&lt;0.001), t(4;14) (39.5% vs 10%, P=0.002), combined t(4;14) and del(13) (32% vs 0%, P=0.001), and del(17p) (28.5% vs 0%, P=0.03). Remarkably, when examined in the context of the VTD arm, high-quality response rates were significantly higher for pts carrying del(13) and t(4;14) vs those who lacked these abnormalities [del(13): CR+nCR:39% vs 24%, P=0.03; ≥VGPR: 71% vs 48%, P=0.001] [t(4;14): ≥VGPR:79% vs 55%, P=0.007)]. An opposite trend was noted for pts in the TD arm, whose probability to attain ≥VGPR was adversely affected by the presence of del(13) (P=0.07) and del(17p) (P=0.03). Variables associated with achievement of CR+nCR in the two arms that retained statistical significance when assessed by multivariate Cox regression analysis included randomization to VTD (P&lt;0.001), light chain only subtype (P&lt;0.001), IgA isotype (P&lt;0.001) and Hb&gt;10 g/dL (P=0.01). In the VTD arm, a positive correlation was observed with del(13) (P=0.006) and t(4;14) (P=0.02). Response to first ASCT with melphalan 200 mg/m2 could be evaluated in 297 pts, of whom 145 randomized to VTD and 152 to TD. Randomization to VTD was closely associated with increased CR+nCR rates (54% vs 29% with TD, P&lt;0.001) and remained statistically significant (P&lt;0.001) also in the multivariate analysis. Additional factors predicting for superior post-ASCT CR+nCR rates in the multivariate setting included light chain only subtype (P&lt;0.001) and IgA isotype (P=0.005). We conclude that randomization to up-front VTD was the strongest and independent factor associated with increased rates of CR+nCR before ASCT. Superiority of VTD to TD pertained in both low-risk and high-risk sub-groups, including the traditionally unfavorable sub-groups carrying del(13), t(4,14) and del(17p). Remarkably, in the VTD arm improved postinduction CR+nCR rates were significantly associated with the presence of del(13) and t(4;14) in the multivariate analysis. Benefit from VTD vs TD as primary induction therapy translated into significantly improved CR+nCR rates after the first ASCT and remained statistically significant when assessed by multivariate analysis.

Evaluation of Serum Free Light Chains In Chinese Multiple Myeloma Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5011-5011
Author(s):  
Chengcheng Fu ◽  
Shiqiang Qu ◽  
Wu Depei
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Elevated Level ◽  
Response Assessment ◽  
Myeloma Cells ◽  
Serum Free ◽  
Β2 Microglobulin ◽  
Measurable Disease

Abstract Abstract 5011 Purpose: Serum Free-Light Chain (sFLC) Assay is a sensitive tool recently used for diagnosis and response assessment of plasma cell disorders, especially in light chain multiple myeloma, nonsecretory multiple myeloma and primary amyloidosis. According to assemble analysis of multiple large-scale clinical research results, guideline of sFLC analysis was introduced by IMWG in 2008. But sFLC assay has not been routinely used in China and the clinical significance of the item has been explored in this study. Patients and Methods: Serum specimens from 36 cases of MM patients identified by IFE were analyzed. The median age was 56.2(36-74). 24(66.7%) patients were male. The M protein type was IgG in 50%, IgA in 22%, IgD in 3%, light chain in 25%. According to D-S staging, 11% pts was inIIA, 58% in IIIA, 31% in IIIB. 8% patients was in±of ISS staging, 17% inII and 75% in III. Normal range for FLC measurements is as follows: κ3.3–13.1 mg/L, λ5.7–26.3 mg/L, and κ/λ ratio of 0.26–1.65. Results: Abnormal rFLCs were detected 100% in 14 newly-diagnosed patients. 86% patients had measurable disease. In κ-MM patients, levels of sFLC-κ were (553.1±471) mg/L; sFLC-λ were (14.2±4) mg/L; the median of rFLC was 32.62. In λ-MM patients, levels of sFLC-κ were (5.3±2.67) mg/L; sFLC-λ were (2503±1043) mg/L; the median of rFLC was 0.002. 22 MM patients were detected during the follow up after treatment. Abnormal clonal rFLC could be found 100% in 3 PD patients, 66.7% in 12 PR/SD patients and 0 in 7 ≥VGPR patients. There was no statistical significance between sFLC and sTLC (p≥0.05). The value of iFLC in ≥VGPR group was statistical different from other response assessment groups (p<0.05). In 24 patients with measurable disease (9 with κ-MM,15 with λ-MM), an elevated level of iFLC was associated with increased myeloma cells in bone marrow and β2-microglobulin, but not with ALB, LDH. Conclusions: sFLC assay is a highly sensitive diagnostic and response monitoring tool for multiple myeloma. An elevated level of iFLC was associated with increased myeloma cells in bone marrow and β2-microglobulin, but not with ALB, LDH in measurable disease. More patients and longer follow-up are needed to further evaluate the diagnostic and prognostic significance of this judgment parameter. Disclosures: No relevant conflicts of interest to declare.

Hevylite™ Assays Detect a Hidden Immunoparesis Associated with Adverse Biology in Myeloma Precursor Disease: A Prospective Clinical Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5065-5065
Author(s):  
Rene Costello ◽  
Karina Espana ◽  
Neha Korde ◽  
Mary Kwok ◽  
Adriana Zingone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prospective Study ◽  
Heavy Chain ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Prospective Clinical Study ◽  
Biological Features ◽  
Increased Risk ◽  
M Spike

Abstract Abstract 5065 Recent studies have found immunoparesis (suppression of an uninvolved heavy-chain immunoglobulin (Ig) isotype; e.g. low quantitative IgA and/or IgM levels in a patient with an IgG M-spike) to be an independent risk factor for transformation from smoldering multiple myeloma (SMM) to multiple myeloma (MM). About 70–80% of SMM patients have evidence of immunoparesis. Among remaining 20–30% of SMM patients without immunoparesis, it is currently unknown whether there could be a hidden immunoparesis, reflected in suppression of the uninvolved light chain counter part of the same heavy-chain Ig isotype (e.g. IgG kappa in a patient with an IgG lambda M-spike), which in turn may be associated with adverse biology. A total of 50 SMM patients were enrolled in the first analysis of this prospective study (target: 124 SMM patients). At baseline, a bone marrow core biopsy/aspirate was conducted, and comprehensive immunohistochemistry and flow cytometry analyses were done to confirm the diagnosis and to generate risk profile data for individual patients. For each patient we obtained peripheral blood at baseline. Using serum, we performed the following clinical analyses: serum protein electrophoresis (SPEP); immunofixation electrophoresis (IFE); serum free light chains (sFLC); and quantitative Ig levels for IgG, IgA, and IgM. Using the Hevylite™ assay on a SPAplus (Specialty Protein Analyzer) platform, for each patient, we measured the heavy-light chain (HLC) protein pairs for the complete pair of the patient's heavy-chain Ig isotype (e.g. IgG kappa and IgG lambda for a patient with an IgG M-spike). Consistent with the literature; overall, we found 32/50 (64%) SMM patients to have immunoparesis of an uninvolved heavy-chain Ig isotype; 31 (97%) of these patients also had suppression of the uninvolved HLC counterpart. Among remaining SMM patients without immunoparesis of an uninvolved heavy-chain Ig isotype, using the Hevylite™ assay we found 8/18 (44%) to have a hidden immunoparesis of the uninvolved HLC counterpart. Compared to SMM patients without any type of Ig suppression, adverse biological features were profound in patients with a hidden immunoparesis of the uninvolved HLC counterpart. For example, the FLC-ratios were more skewed (mean: 14.2 vs. 2.5), the distribution of abnormal/normal plasma cells was more pronounced (90.1% vs. 80.3%), the concentration of the M-spike was higher (1.4 g/dL vs. 1.0 g/dL), and the plasma cell percentage in the bone marrow was higher (15.1% vs. 11.9%). In conclusion, using the Hevylite™ assay we identified, for the first time, among SMM patients without immunoparesis, a hidden immunoparesis of the uninvolved HLC counterpart, associated with adverse biological features. Our ongoing prospective study will evaluate whether immunoparesis of the uninvolved HLC counterpart is associated with an increased risk of progression to MM. Disclosures: No relevant conflicts of interest to declare.

An Intact Immunoglobulin IgAλ Multiple Myeloma Patient Exhibiting Light Chain Escape

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5008-5008
Author(s):  
Maria Kraj ◽  
Barbara Kruk ◽  
Krzysztof Warzocha ◽  
Andrzej Szczepinski ◽  
Kelly Endean ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Light Chain ◽  
Plasma Cells ◽  
Induction Treatment ◽  
Mild Renal Impairment ◽  
Multiple Myeloma Patient ◽  
Monoclonal Protein ◽  
Serum And Urine

Abstract Abstract 5008 A 48 year old man was referred to the Institute of Hematology and Transfusion Medicine, Warsaw, Poland in April 2008 with anemia (Hemoglobin; 10. 4 g/dl) and mild renal impairment (eGFR; 75. 4 mL/min/1. 73m2). An initial diagnostic monoclonal protein screen (serum protein electrophoresis (SPE), serum immunofixation electrophoresis (IFE) and serum free light chain (FLC) analysis) revealed an IgAλ monoclonal protein (0. 8g/dL) with monoclonal serum FLC and an abnormal serum FLC κ/λ ratio (0. 0001; RI, 0. 26–1. 65). A bone marrow biopsy at that time confirmed 60% involvement of monoclonal λ - restricted plasma cells; a bone survey did not detect any osteolysis. The patient was diagnosed with multiple myeloma (MM) (ISS stage I, Durie and Salmon stage IA) and was initially treated with 6 cycles of vincristin, doxorubicin and dexamethasone (VAD). The patient responded well to the induction treatment and subsequently underwent a successful autologous stem cell transplantation (ASCT). The patient was monitored for 3 years subsequent to the ASCT with both serum and urine electrophoresis, serum FLC analysis (Freelite) and heavy chain/light chain (HLC) immunoassays (Hevylite). Sixteen months following the ASCT the dFLC (involved λ FLC– uninvolved κ FLC) concentration began to increase, the FLC κ/λ ratio became abnormal with a trace of λ Bence Jones protein (BJP) detected by urine IFE. However, both SPE and IFE were normal and the HLC ratio (IgAλ/IgAκ) was within the normal range. During the next 9 months the dFLC continued to increase and a λ BJP could now be clearly detected on the urine IFE. 27 months following the ASCT the patient sustained a pathological fracture of the tibiae and was referred to our centre 4 months later. At this point, the dFLC concentration was highly elevated (3168 mg/L) with a λ BJP detectable by both serum and urine IFE. However, there was no detectable monoclonal intact immunoglobulin by serum IFE or HLC analysis, indicating disease relapse by a separate FLC clone; referred to as light chain escape (LCE). A bone marrow biopsy revealed 15% involvement of λ restricted plasma cells; this time a bone survey identified osteolysis. The patient was diagnosed with progression of multiple myeloma and received 6 cycles of bortezomib, cyclophosphamide and dexamethasone (VCD regimen). He responded well to treatment and 3 years following the ASCT achieved a CR as indicated by a normalized κ/λ FLC ratio, negative immunofixation with 1–3% bone marrow plasma cells. The patient is now well and able to continue with normal life. In this case study the increase in the dFLC levels was the first indication of disease progression and highlights the importance of monitoring intact immunoglobulin MM patients with serum FLC immunoassays for early detection of LCE. Disclosures: Endean: The Binding Site Group Ltd: Employment. Harding:Binding Site: Employment.

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