Seeking light-chain amyloidosis very early: The SAVE trial—identifying clonal lambda light chain genes in patients with MGUS or smoldering multiple myeloma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8010-8010 ◽  
Author(s):  
Ping Zhou ◽  
Adin Kugelmass ◽  
Denis Toskic ◽  
Amandeep Godara ◽  
Teresa Fogaren ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Plasma Cells ◽  
Unmet Need ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Rt Pcr ◽  
Smoldering Multiple Myeloma ◽  
Increased Risk ◽  
Germline Genes

8010 Background: In systemic AL amyloidosis (AL), caused by clonal Ig free light chains (LC) produced in 75% of cases by λ clones, patients often present with advanced organ damage, making earlier diagnosis a critical unmet need. Five λ IGLV germline genes account for 75% of AL λ-type ( IGLV 6-57, 1-44, 2-14, 1-51, 3-1) (Blood 2017;129:299), representing 56% of all AL patients. Relative risk of AL versus MM with these clonal genes can be high (7.3, 6-57; 2.5, 1-44), intermediate (1.7, 2-14; 1.2, 1-51) or low (0.8, 3-1) (Amyloid 2009;16:1). Progression to AL from smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS) occurs but is not well appreciated (JCO 2014; 32:2679). SAVE is a trial for λ SMM or λ MGUS patients with a κ:λ FLC ratio < 0.26 and difference between involved and uninvolved FLC > 23mg/L (JCO 2014;32:2699). Methods: Eligible patients ship peripheral blood (PB) or bone marrow (BM) samples to us for RT-PCR with cDNA from CD138+ cells, using primers for the Vλ families (Blood 2001;98:714). Amplicons are sequenced and the IGLV germline genes identified in IMGT (ImMunoGene-Tics, www.imgt.org). If the germline gene is AL-related, further evaluation is pursued. Results: Twenty asymptomatic λ patients from 18 states have been enrolled (3M, 17F) and 23 PB and 4 BM specimens obtained. Medians of months from diagnosis, involved FLC, κ:λ ratios, MNC and CD138-selected cells were 20.5 months, 113mg/L, κ:λ 0.06, 8.1x106 (0.8-24) and 3x105 (0-30), respectively. Seventeen patients have had IGLV genes identified, 12 with the first and 5 with additional specimens including 4 BM. Increased risk of AL was identified in 7 patients, 2 of whom had undiagnosed AL (both with IGLV2-14 germline genes). One patient with SMM diagnosed in 2016 had AL λ-type with GI involvement and is 9 months status post MEL 200 stem cell transplant (SCT), and the second with SMM diagnosed in 2009 had cardiac AL λ-type by heart biopsy with an NT-proBNP 171 (but with a suggestive MRI) and is en route to SCT. Conclusions: The SAVE trial enables early diagnosis of AL λ-type based on the λ IGLV gene used by the clonal plasma cells. By RT-PCR in this pilot study we identified the clonal λ gene 85% of the time. Earlier diagnosis will enable treatment with effective therapy such as MEL 200 SCT. Clinical trial information: NCT02741999.

Biclonal Multiple Myeloma with Monoclonal Free IgG3 Heavy Chain and kappa Free Light Chains.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4768-4768
Author(s):  
Alex G. Richter ◽  
Stephen Harding ◽  
Steve Rimmer ◽  
Guy Pratt ◽  
Aarnoud Huissoon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Western Blot ◽  
Heavy Chain ◽  
Light Chain ◽  
Lymphoproliferative Disorder ◽  
Plasma Cells ◽  
Light Chains ◽  
Cell Transplant ◽  
Free Light Chains ◽  
Night Sweats

Abstract Background: Heavy chain disease (HCD) is a rare lymphoproliferative disorder characterized by a monoclonal heavy chain (HC) unattached to a light chain (LC). IgGHCD or γHCD typically presents as a lymphoproliferative disorder with lymphadenopathy and hepatosplenomegaly. Myeloma has been described associated with γHCD but only with a second intact Ig paraprotein. This report describes a unique presentation of multiple myeloma with monoclonal free γ3HC and kappa free light chains. Case: A 34 year old gentleman presented with mild persistent neutropenia following two episodes of pneumonia, 18 months previously. He admitted to persistent night sweats but no other significant history. Baseline investigations revealed a mild anaemia, neutropenia and a large IgG paraprotein with no associated light chain. Bone marrow aspirate and trephine confirmed myeloma. The patient was treated with cyclophosphamide, thalidomide and dexamethasone and has had a very good partial remission. He is awaiting a sibling allogeneic peripheral blood stem cell transplant. Investigations and results: Serum Electrophoresis confirmed a large IgG paraprotein (23g/l) with no associated light chain in the serum and identified as γ3 subclass by radial immunodiffusion. Western blot showed the γ3HC was truncated with a large deletion. Markedly elevated free kappa (κ) LC (503.58 mg/l [3.30–19.4]) were found in the serum with gross skewing of the kappa/lambda ratio. Urine electrophoresis revealed separate γHC and κ LC paraproteins. Western blot of the fractionated urine protein demonstrated different sized κLC aggregates. Flow cytometry of the marrow aspirate revealed an unusual staining pattern; CD5,19,38,45+ve and CD20,22,23,34,56,138 –ve plasma cells. Cytoplasmic staining revealed 2 distinct populations of plasma cells, the first producing γ3HC and the second only free κLC. Cytogenetics and FISH analysis for 14q, p53 and c-myc abnormalities were normal. Discussion: This is the first description of a Biclonal Myeloma with separate plasma cell populations producing γ3HC and κLC paraproteins. The biclonality confirms the free HC occurs as a result of abnormal synthesis not cleavage. The clinical and immunological findings are clearly different to typical findings in both γ3HCD and Myeloma. HCD has an appalling prognosis and this case is likely to have been ‘smouldering’ for 18 months, evidenced by the 2 pneumonias and persistent night sweats. There is no lymphadenopathy or organomegaly associated with γ3HCD. The immunophenotype of the malignant plasma cells is unique. Other atypical features include frank proteinuria, with a HC in the urine, but normal renal function and no radiological or biochemical evidence of bone involvement. We propose that this unique biclonal myeloma has distinct immunological and clinical features.

scholarly journals The Clinical Features of Multiple Myeloma with AL Amyloidosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-10
Author(s):  
Junichiro Nashimoto ◽  
Moe Nomura ◽  
Hirofumi Irita ◽  
Kota Sato ◽  
Kanji Miyazaki ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Features ◽  
Light Chain ◽  
Mayo Clinic ◽  
Plasma Cells ◽  
Staging System ◽  
Stage I ◽  
P Value ◽  
Al Amyloidosis ◽  
Hepatic Amyloidosis

Background Multiple myeloma and AL amyloidosis are both caused by the clonal proliferation of the abnormal plasma cells. Although, the difference of the genetic features of multiple myeloma and AL amyloidosis has been reported, we see some patients present with both cases. We retrospectively investigated the clinical features of patients diagnosed with multiple myeloma and AL amyloidosis. Methods We reviewed medical records of patients who were diagnosed with multiple myeloma and AL amyloidosis before initiating treatment during January 2009 to November 2019 in our institution. We excluded patients who did not reach 10% of the plasma cells in the bone marrow. Patients diagnosed with light chain deposition disease were excluded. Treatment regimens were at the discretion of the treating physician. Results Forty-two patients were diagnosed with multiple myeloma and AL amyloidosis. The median follow-up time since diagnosis was 20 months [0-89]. The median age was 63-year-old [43-85]. There was no difference between the sex (male: female=1:1). Twenty-nine (69.0%) patients had lambda type of light chain. Patients with ISS stage I, II, and III were 13(31.7%), 21(51.2%), and 7(17.1%). Patients with R-ISS stage I, II, and III were 4(10.3%), 30(76.9%), and 5(12.8%). Patients with Revised Mayo Clinic AL amyloidosis Staging System 1, 2, 3, and 4 were 3(10.0%), 4(13.3%), 8(26.7%), and 15(50.0%). Twelve (35.3%), 2 (6.9%), 1 (3.4%) and 1 (4.0%) patients had t(11;14), t(4;14), t(14;16) and del(17p) by FISH analysis, respectively. Fourteen (33.3%), 16(38.1%), and 8(19.0%) patients were diagnosed with cardiac, renal, and hepatic amyloidosis, respectively. Thirty-five (83.3%) patients received Bortezomib containing regimen for the initial treatment (e.g., Bortezomib+Dexamethasone(7.1%), Cyclophosphamide+Bortezomib+Dexamethasone(23.8%), Bortezomib+Melphalan+Dexamethasone(7.1%), Bortezomib+Melphalan+Prednisolone(9.5%), Bortezomib+Lenalidomide+Dexamethasone(35.7%)). Thirteen (31.0%) patients underwent autologous stem cell transplantation with high dose melphalan. Median PFS was 25 months and the median OS was 82 months. There were no significant differences in OS between the I-SSS, R-ISSS, and Revised Mayo Clinic AL amyloidosis Staging System groups. Patients diagnosed with cardiac or hepatic amyloidosis had significantly worse outcome. The median OS diagnosed with and without cardiac amyloidosis were 14 and 28 months (p value = 0.034), and the median OS diagnosed with and without hepatic amyloidosis were 8 and 24 months (p value = 0.012). Conclusion Multiple myeloma with AL amyloidosis, especially cardiac or hepatic amyloidosis, has a poor prognosis even if treated with novel agents. Searching for the optimal treatment for these patient groups remains to be an issue. Disclosures Nashimoto: Janssen: Speakers Bureau; Celgene: Speakers Bureau. Tsukada:Takeda pharmaceutical co: Speakers Bureau. Ishida:Ono pharmaceutical co: Speakers Bureau; Takeda pharmaceutical co: Speakers Bureau; Janssen: Speakers Bureau; Celgene: Speakers Bureau. Suzuki:Bristol-Myers Squibb, Celgene and Amgen: Research Funding; Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria.

scholarly journals Seeking AL Amyloidosis Very Early: The SAVE Trial — Identifying Clonal Lambda Light Chain Genes in Patients with MGUS or Smoldering Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1903-1903 ◽  
Author(s):  
Ping Zhou ◽  
Adin Kugelmass ◽  
Denis Toskic ◽  
Melissa Warner ◽  
Lisa X. Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Variable Region ◽  
Organ Damage ◽  
Al Amyloidosis ◽  
Germline Gene ◽  
Fat Pad ◽  
Rt Pcr ◽  
Patients At Risk

Abstract INTRODUCTION : Currently patients with systemic AL amyloidosis (AL) are not identified until they are sick due to end-organ damage, usually a result of elevated clonal Ig free light chains (FLC) produced by λ clones in 75% of cases. Delays in diagnosis put patients at risk of developing irreversible organ damage making AL much harder to treat. Only about 25% of newly diagnosed AL patients are eligible for melphalan (MEL) based stem cell transplant (SCT). To extend the overall survival and quality of life of AL patients, early diagnosis is critical. A retrospective study of AL λ-type patients using the US Department of Defense serum repository showed that 100% of patients had a monoclonal FLC present for up to 4 years preceding diagnosis, 92% of whom had a difference between the pathologic and non-involved FLC (dFLC) of >23 mg/L (J Clin Oncol 2014;32:2699). Progression to AL from precursor states such as monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) is well described but often not clinically appreciated. SAVE is an internet-based diagnostic trial (NCT02741999) for patients with λ MGUS or SMM with a κ:λ ratio < 0.26 and dFLC > 23mg/L. Using peripheral blood and, when available, marrow aspirates, we try to identify each patient's λ germline variable region (IGLV) donor gene. Five IGLV genes account for 75% of AL λ-type (IGLV1-44. 1-51, 2-14, 3-1, 6-57) (Blood 2017;129:299). Based on data in AL-Base, relative risk of AL versus myeloma with these clonal genes can be significantly high (7.3, 6-57; 2.5, 1-44), intermediate (1.6, 2-14; 1.2, 1-51) or low (0.8, 3-1) (Amyloid 2009;16:1). MATERIAL S & METHODS : Patients provide written consent to be screened by medical records review. Eligible patients ship peripheral blood (PB) or marrow (BM) samples to us obtained only at times of routine clinical testing. We select CD138+ cells from PBMNC or BM for whole-cell RNA preparation (RNeasy Mini Kit, QIAGEN, Valencia, CA) and cDNA synthesis (ThermoScript RT-PCR System, Invitrogen Life Technologies, Carlsbad, CA) for storage at -80o C. Primer sets are degenerate FR1 and 5' CR primers for the Vλ1, Vλ2, Vλ3 and Vλ6 families (Blood 2001;98:714). Three RT-PCR products of appropriate size per clone are sent to our core facility for sequencing. We then use the sequences to search for the corresponding IGLV germline gene in IMGT (ImMunoGene-Tics, www.imgt.org). Patients and their MDs are notified of the results and, if the germline donor is associated with AL with high or intermediate risk, further evaluation for AL is discussed and pursued. RESULTS : Twenty asymptomatic λ patients from 13 states thus far have consented to be screened for SAVE, and 19 enrolled (3M, 16F). Twenty-three PB and 4 BM specimens have been obtained. Median months from diagnosis to receipt of first specimen was 15, involved FLC 107mg/L and κ:λ ratio 0.09. Median PBMNC and CD34-selected cells were 8x106 (2.6-24) and 3x105 (0-6) respectively. Twelve patients had IGLV genes identified by PCR with the first specimen; 5 sent additional specimens including 3 BM. There were no differences in CD34-selected cell numbers or λ light chain levels between first-specimen PCR successes and failures. Seventeen patients have had IGLV genes identified: four 2-14, three 1-44, two 3-1 and eight others. Increased risk of AL was identified in 7 patients who were screened with abdominal fat pad studies. One of the 7 (with IGLV2-14) had a positive fat pad and was then diagnosed with AL λ-type with GI involvement. She was induced with 4 cycles of bortezomib-based therapy and is now 3 months status post an uncomplicated MEL 200 SCT. Two SMM patients (of 19) have proceeded to symptomatic myeloma requiring therapy. CONCLUSIONS : The SAVE trial may enable early appreciation of risk of AL λ-type based on the variable region germline gene used by the clonal plasma cells. In λ MGUS and SMM patients with elevated lambda FLC, below normal ratios, and dFLC > 23mg/L, the clonal gene can be identified by RT-PCR with CD138-selected cells from a single peripheral blood specimen 70% of the time. Close follow up of patients at risk may reduce the likelihood of eventually being diagnosed with advanced organ involvement. Earlier diagnosis may permit prompt induction therapy if required and expanded application of MEL 200 SCT, a preferred treatment for patients with < 10% clonal marrow plasma cells at diagnosis or after induction (Biol Blood Marrow Transplant 2016;22:1729). Disclosures No relevant conflicts of interest to declare.

scholarly journals Effects of Amyloid Light-Chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-Center Retrospective Study

2020 ◽  
Author(s):  
Junhui Xu ◽  
Mangju Wang ◽  
Ye Shen ◽  
Miao Yan ◽  
Weiwei Xie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Light Chain ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Al Amyloidosis ◽  
Smoldering Multiple Myeloma ◽  
Independent Prognostic Significance ◽  
Amyloid Light Chain

Abstract Background: Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of symptomatic and smoldering multiple myeloma with AL amyloidosis is not particularly clear.Methods: Patients with symptomatic and smoldering multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information were collected from first presentation to death or until the last available clinical follow-up. The patients’ survival and outcomes were analyzed, and the relationships between the clinical parameters and survival were also assessed.Results: Compared with symptomatic multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/ml (P<0.001), ALP>187.5IU/L (P=0.032) and ALB<25g/L (P<0.001). Similarly, compared with smoldering multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/ml (P=0.030) and Alb<25g/L (P=0.024). The existence of AL amyloidosis especially the heart involvement was related to shorter long-term survival of symptomatic and smoldering multiple myeloma according to univariate analyses. Renal involvement and gastrointestinal tract involvement had an impact on the prognosis of smoldering multiple myeloma but not on symptomatic multiple myeloma. Cox regression model for overall survival detected BNP≧700pg/ml in symptomatic multiple myeloma having independent prognostic significance (RR=2.455, P=0.004). Interestingly, BNP at diagnosis was significantly correlated with cardiac amyloidosis (r=0.496, P<0.001).Cox regression model for overall survival detected the presence of AL amyloidosis in smoldering multiple myeloma having independent prognostic significance (RR=8.741, P=0.002).Conclusions: AL amyloidosis is an independent poor prognostic factor for not only symptomatic multiple myeloma but also smoldering multiple myeloma is mainly because involvements of important organs especially the heart. AL amyloidosis probablely has a greater impact on the prognosis of smoldering multiple myeloma than symptomatic multiple myeloma.

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 &lt; 3 g/dL; and serum M protein ≥ 3 g/dL but bone marrow plasma cells &lt; 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

Performance of Free Light Chain Assays in Clinical Practice.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 757-757 ◽  
Author(s):  
Jerry A. Katzmann ◽  
Angela Dispenzieri ◽  
Roshini S. Abraham ◽  
Robert A. Kyle
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Light Chain ◽  
Test Performance ◽  
Plasma Cells ◽  
Clinical Laboratory ◽  
Lymphoproliferative Disease ◽  
Free Light Chain ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease

The quantitative assay for free light chains (FLC) is a recently introduced commercial product (FREELITETM, The Binding Site, Ltd.) that has been reported to be sensitive and specific for detecting and monitoring free light chain diseases such as primary systemic amyloidosis (AL), light chain deposition disease (LCDD), non-secretory multiple myeloma (NSMM), and LCMM (light chain multiple myeloma). We have prospectively evaluated the test performance in clinical practice. Results : In 2003, our Clinical Laboratory received samples for FLC assays from 1020 Mayo Clinic patients. The majority of these patients (88%) had plasma cell disorders (PCD). All 120 patients who did not have PCD had normal K/L FLC ratios. Among these, 52 had non-AL amyloidosis: localized amyloid (23), hereditary (16), senile (6), secondary (3), and amyloid of unknown type (4). The 68 other patients who did not have a PCD were being tested because of peripheral neuropathy, rule out AL, anemia, proteinuria, lymphoproliferative disease, and a number of other indications with small numbers of patients (n=13). Among the monoclonal gammopathy patients were 330 with MM, 269 AL, 115 MGUS, 72 SMM, 22 plasmacytomas, 20 NSMM, 9 macroglobulinemia, 7 LCDD, and a variety of other diagnoses with smaller numbers of patients. The sensitivity of the K/L FLC ratio was 100% in LCDD (7/7) and 70% in NSMM (14/20). The 6 NSMM patients with normal K/L FLC ratios had all been treated with SCT and 5 of the 6 had achieved hematologic remission by bone marrow plasma cells. Among the 110 AL patients who had not been previously treated and who had a FLC assay performed within 120 days of diagnosis, the sensitivity of the K/L FLC ratio was 92% compared to 71% for serum IFE and 84% for urine IFE. Using all 3 assays, there was 99.1% (109/110) sensitivity for detecting monoclonal light chain in AL. Conclusion : The performance of the FLC assay in this prospective analysis matches the results from published retrospective validation studies.

scholarly journals Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 785-789 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
Terry M. Therneau ◽  
Dirk Larson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Plasma Cells ◽  
Risk Model ◽  
Free Light Chain ◽  
M Protein ◽  
Serum Samples ◽  
Baseline Serum ◽  
Increased Risk ◽  
Risk Of Progression

We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering multiple myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased risk of progression to active myeloma. Baseline serum samples obtained within 30 days of diagnosis were available in 273 patients with SMM seen from 1970 to 1995. At a median follow-up of surviving patients of 12.4 years, transformation to active disease has occurred in 59%. The best breakpoint for predicting risk of progression was an FLC ratio of 0.125 or less, or 8 or more (hazard ratio, 2.3; 95% CI, 1.6-3.2). The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of bone marrow plasma cells (BMPCs) and size of serum M proteins (BMPC ≥ 10% and serum M protein ≥ 3 g/dL; BMPC ≥ 10% but serum M protein < 3 g/dL; and serum M protein≥ 3 g/dL but BMPC < 10%). Incorporating the FLC ratio into the risk model, the 5-year progression rates in high-, intermediate-, and low-risk groups were 76%, 51%, and 25%, respectively. The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM.

scholarly journals Splenic plasma cells can serve as a source of amyloidogenic light chains

Blood ◽  
2009 ◽  
Vol 113 (7) ◽  
pp. 1501-1503 ◽  
Author(s):  
Alan Solomon ◽  
Sallie D. Macy ◽  
Craig Wooliver ◽  
Deborah T. Weiss ◽  
Per Westermark
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Light Chain ◽  
Plasma Cells ◽  
The Body ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Hematopoietic Organ ◽  
Significant Evidence

Abstract Bone marrow-derived clonal plasma cells, as found in systemic amyloidogenic light chain–associated (AL) amyloidosis, are presumed to be the source of light chains that deposit as fibrils in tissues throughout the body. Paradoxically, people with this disorder, in contrast to multiple myeloma, often have a low percentage of such cells, and it is unknown whether this relatively sparse number can synthesize enough amyloidogenic precursor to form the extensive pathology that occurs. To investigate whether another hematopoietic organ, the spleen, also contains monoclonal light chain–producing plasma cells, we have immunostained such tissue from 26 AL patients with the use of antiplasma cell, antifree κ and λ, and anti-VL subgroup-specific monoclonal antibodies (mAbs). In 12 cases, there was statistically significant evidence of a monoclonal population bearing the same κ or λ isotype as that within the bone marrow and identical to the amyloid. Our studies have shown that the spleen may be another source of amyloidogenic light chains.

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
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