An Unusual Cause of Generalized Swelling

Amyloidosis and multiple myeloma are included in the same spectrum of clonal plasma cell disorder. Amyloidosis can present with localized deposits or manifest as systemic disease involving multiple organs such as kidney, heart, intestine. Free Ig subunits ,mostly light chains secreted by a single clone of B cells, are the cause of the most frequent and severe amyloidosis affecting the kidney. The incidence of AL amyloidosis is nine per 1 million populations per year. Amyloid deposists are found in approximately 10% of all patients with myeloma and in 20% of those with pure light chain myeloma[1].Here we are reporting a case who initially presented with generalized swelling and subsequently found to have AL amyloidosis involving multiple organs due to multiple myeloma.J Dhaka Medical College, Vol. 26, No.2, October, 2017, Page 173-177

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Recurrent syncope and cardiac arrest in a patient with systemic light chain amyloidosis treated with bortezomib

Hematology Reports ◽

10.4081/hr.2016.6417 ◽

2016 ◽

Vol 8 (2) ◽

Cited By ~ 2

Author(s):

Navin Jaipaul ◽

Alexander Pi ◽

Zhiwei Zhang

Keyword(s):

Multiple Myeloma ◽

Cardiac Arrest ◽

Light Chain ◽

Proteasome Inhibitor ◽

Medical Literature ◽

Systemic Disease ◽

Al Amyloidosis ◽

Multiple Organs ◽

History Of ◽

Possible Cause

About 10-15% of patients with multiple myeloma develop light chain (AL) amyloidosis. AL amyloidosis is a systemic disease that may involve multiple organs, often including the heart. It may present clinically with bradyarrhythmia and syncope. The proteasome inhibitor bortezomib has been used with clinical efficacy in treating patients with AL amyloidosis but also implicated as a possible cause of cardiomyocyte injury. We report a case of a 48-year-old man with AL amyloidosis and increased frequency of syncope and cardiac arrest after starting bortezomib. The biologic and clinical plausibility of a heightened risk for cardiac arrest in patients with cardiac AL amyloidosis and history of syncope being treated with bortezomib is a possibility that is not well documented in the medical literature and warrants further investigation.

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Genomic Landscape of Immunoglobulin Light Chain (AL) Amyloidosis and Comparative Analyses with Related Malignant Plasma Cell Disorder- Multiple Myeloma

Blood ◽

10.1182/blood.v118.21.809.809 ◽

2011 ◽

Vol 118 (21) ◽

pp. 809-809

Author(s):

Vishwanathan Hucthagowder ◽

Jahangheer Shaik ◽

Mark Fiala ◽

Jacob Paasch ◽

Rakesh Nagarajan ◽

...

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Light Chain ◽

Copy Number ◽

Al Amyloidosis ◽

Immunoglobulin Light Chain ◽

Genomic Changes ◽

Genomic Landscape ◽

Plasma Cell Disorder ◽

Cell Disorder

Abstract Abstract 809 Immunoglobulin light chain amlyloidosis (AL) is a rare plasma cell disorder characterized by deposition of misfolded light chains in various organ systems with an average survival of 1–2 years. AL is also the most common form of systemic amyloidosis with 1200–3200 newly diagnosed cases reported annually in the United States. Very little is known regarding specific genomic aberrations associated with AL-amyloidosis. Aside from the light chain selection, no phenotypic or genetic features have been identified that distinguish AL amyloidosis from other plasma cell dyscrasias. Understanding the genetics of AL and the molecular mechanisms involved in amyloid formation may lead to early diagnosis and the identification of novel drug targets and therapies. We therefore have attempted to study the genomic landscape of AL patients and MM for comparison. Genomic copy number and loss of heterozygosity (LOH) analyses were performed on DNA derived from tumor (CD138 sorted cells) and matched germline (skin) from biopsy proven AL patients using Affymetrix single nucleotide polymorphism (SNP) 6.0 arrays. Numerous genomic changes with gains in chromosome 1q, 6, 9, 11q, 15, 19 and 21 and loss on chromosome 1p, 2q, 8, 10, 12, 13, 14, 16, 18, 20 and 22 were observed in more than 10% of the patients. Recurrent genomic changes in about 249 segments involving 457 genes were present in about 1/3 of AL patients. In particular, deletion of IGK, IGH, PIK3CA, FLT3, RB1, PCDH9, GPC6, RASA3, ADAM6 genes and amplification of CFHR1, JAK2, GCNT1, TSC1, PGR genes were observed. Gene network analysis showed five distinct major modules consisting of 51 distinct elements and involving PDGF, TP53, interleukin signaling, TRKA signaling, cell cycle and mitotic pathways were enriched. Allele specific copy number analysis in tumor (ASCAT) profile showed increased ploidy status of the AL genome in 47% of the assessed patients. LOH was observed in chromosomes 4, 5, 6, 8, 9, 12, 13, 18 and 22 in 30% of patients, ranging from 5Mb to entire chromosome. Furthermore, genomic comparisons of AL with multiple myeloma (MM) showed the typical archetype of myeloma's signature with exception of gain of chromosomes 3, 5, 7 and loss of chromosome 6q and 8p. Interestingly deletion of IGH, IGK locus and PIK3CA gene were observed at a higher frequency in AL patients. Categorical analysis using isotype specific classification in AL showed a significantly higher frequency of deletion in chromosome 14, 13, 8 and amplification of chromosome 9q in the kappa type than lambda isotype. To the best of our knowledge, this is the first ultra-high resolution study of the genomic landscape of AL amyloidosis. In this study, we have found several novel genes and pathways associated with this rare disease. The numerous copy number alterations of AL thus reflect the genomic complexity and the heterogeneity of this disease. Additional genome-wide analysis in a larger panel with target organ stratified patients is under way and may further our understanding of genetic changes specifically associated with AL. Disclosures: No relevant conflicts of interest to declare.

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A Pre-Existing Plasma Cell Disorder Occurs in Most Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v112.11.1693.1693 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1693-1693 ◽

Cited By ~ 2

Author(s):

Brendan M Weiss ◽

Pramvir Verma ◽

Jude Abadie ◽

Robin Howard ◽

Michael Kuehl

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Light Chain ◽

Medical Center ◽

Walter Reed Army Medical ◽

Cell Transplant ◽

Serum Samples ◽

Published Evidence ◽

Plasma Cell Disorder ◽

Cell Disorder

Abstract Background. A pre-existing plasma cell disorder (PPCD), such as monoclonal gammopathy of undetermined significance (MGUS), is thought to be present in at least one-third of patients presenting with symptomatic multiple myeloma (MM). However, no study has comprehensively evaluated the proportion of patients with MM that had a PPCD by laboratory testing on pre-diagnostic sera. Methods. The Walter Reed Army Medical Center autologous stem cell transplant database was cross-referenced with the Department of Defense Serum Repository (DoDSR) database, which catalogs serum samples collected every 2 years on over 4 million active-duty service members. All samples 32 years prior to the diagnosis of MM were retrieved. Serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE) and serum free light chain analysis (sFLC) (The Binding Site, San Diego, CA) were performed on all samples. A PPCD was defined as a positive SPEP, IFE or abnormal sFLC ratio. Results. Serum samples prior to the diagnosis of MM were available for 30/90 patients, and the median number of samples per patient was 3.5 (range, 1–14). The median age at diagnosis of MM was 48.1 yrs (29–67), with 96% male, 53% Caucasian, and 47% African-American. The Ig isotype of MM was IgG 76%, IgD 10%, light-chain 7%, and non-secretory 7%. A PPCD was detected in 27/30 patients (90%, 95% CI 74–97%). The initial PPCD was detected by sFLC alone in 6/27 (22.2%), IFE alone 2/27 (7.4%), SPEP+IFE 5/27 (18.5%), SPEP+IFE+sFLC 13/27 (48.1%) and IFE+sFLC 1/27 (3.7%). There were 4 patients whose only positive sera was 2.5–3.5 years prior to diagnosis, with all preceding sera negative. Conclusions. First, a pre-existing plasma cell disorder is present in most MM patients at least 2.5 years prior to diagnosis. Second, consistent with published evidence for a small fraction of patients with high risk MGUS, 4/30 patients were documented to progress rapidly through an MGUS phase to MM. Third, 4/4 patients with light chain only or non-secretory MM had a PPCD that was detected only by sFLC, thereby indicating that all these tumors are preceded by a light chain only or non-secretory PPCD.

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Incidentally Detected Amyloid Light-Chain Amyloidosis Caused by Monoclonal Gammopathy of Undetermined Significance: Possible Time-Dependent Change in Colonic Findings

Case Reports in Gastroenterology ◽

10.1159/000494919 ◽

2018 ◽

Vol 12 (3) ◽

pp. 737-746

Author(s):

Toshiro Fukui ◽

Yuji Tanimura ◽

Yasushi Matsumoto ◽

Shunsuke Horitani ◽

Takashi Tomiyama ◽

...

Keyword(s):

Plasma Cell ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Amyloid Deposition ◽

Fecal Occult Blood ◽

Al Amyloidosis ◽

Plasma Cell Disorder ◽

Amyloid Light Chain ◽

Cell Disorder ◽

Undetermined Significance

Amyloid light-chain (AL) amyloidosis is associated with plasma cell disorder and monoclonal light chains. This type of amyloidosis is the prominent type involving the gastrointestinal tract. Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell disorder and a known precursor of more serious diseases. A 72-year-old male was treated for high blood pressure, diabetes, and gout at the clinic of a private physician. Due to a positive fecal occult blood test discovered during colon cancer screening, he underwent colonoscopy and was diagnosed with adenomatous polyps by biopsies. Two months later, he was referred to our hospital for endoscopic resection of the polyps. Although the polyps were successfully removed, a colonoscopy revealed two types of ulcerative lesions. Immunohistopathological evaluations obtained from these lesions and polyps confirmed amyloid deposition. Although esophagogastroduodenoscopy results were normal, a biopsy specimen from the patient’s stomach showed the same type of amyloid deposition. Immunoelectrophoresis showed M-proteins for anti-IgG-λ in the serum and λ type Bence-Jones protein in the urine. His blood, bone marrow, and urine test results led to a diagnosis of MGUS. A coronary angiography revealed multivessel stenosis, and the patient’s cardiac function improved after coronary artery stenting. Hereafter, a combination therapy with bortezomib, lenalidomide, and dexamethasone is planned. This is a case report of systemic AL amyloidosis caused by MGUS, which was incidentally detected by colonoscopy.

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Lenalidomide/Melphalan / Dexamethasone Chemotherapy In 50 Patients With Newly Diagnosed Amyloid Light Chain Amyloidosis: First Results Of a Prospective Single Center Phase 2 Study (Leomex)

Blood ◽

10.1182/blood.v122.21.1993.1993 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1993-1993

Author(s):

Stefan O Schonland ◽

Tilmann Bochtler ◽

Axel Benner ◽

Marianne Gawlik ◽

Christoph Kimmich ◽

...

Keyword(s):

Plasma Cell ◽

Light Chain ◽

Cardiac Amyloidosis ◽

High Dose ◽

Al Amyloidosis ◽

Newly Diagnosed ◽

Number Of Patients ◽

Plasma Cell Disorder ◽

Amyloid Light Chain ◽

Cell Disorder

Abstract Introduction Amyloid light chain (AL) amyloidosis is a rare and life-threatening protein-misfolding disorder that is causedin most cases by a monoclonal plasma cell disorder. The goal of chemotherapy is to normalize the involved free light chain in serum which leads to an improvement or at least stabilization of organ function in most of these patients. A major challenge is the high treatment-related mortalityand toxicity in patients with advanced cardiac amyloidosis. Study design We performed a prospective single centerphase 2 trial with50 patients not eligible for high-dose treatment.Main inclusion criteria were: newly diagnosed and biopsy proven AL amyloidosis, significant organ involvement, age < 75 yrs and creatinine clearance > 40 ml/min. Treatment schedule was 6 cycles of an oral treatment with lenalidomide 10 mg day 1-21, melphalan 0.15 mg/kg day 1-4 and dexamethasone 20 mg day 1-4 every 4 weeks (L-M-dex). Primary endpoint was the rate of complete remissions (CR) of the underlying plasma cell disorder after 6 treatment cycles. Patients who received at least 3 cycles were eligible for hematologic remission (HR=CR+PR) analysis (At the time of study initiation “very good partial remission”in AL amyloidosis was not yet defined). The study was financially supported by Celgene. Patients and Methods Fiftypatients were included between 2009 and 2012. The median age was 67 years. 74% of patients had cardiac involvement. Outcome was compared with a historical group of 53 AL patients who received M-dex between 2004 and 2009 and fulfilled the same in- and exclusion criteria (patient characteristics see table). Results Forty-five patients (90%) completed 3 cycles and 35 patients (70%) completed 6 treatment cycles; overall 253 cycles could be administered. Reasons of discontinuation were toxicity in 6 patients (including one treatment-related death in the first cycle) or AL progression (9 patients). Ninety adverse events (AE) ≥ CTC grade 3 were recorded including 16 severe AEs. Seventeen hematologic AEs were observed (neutropenia 76%, CTC grade 4 in 2 patients). Most common non-hematologic AE was worsening of cardiac function or symptoms of autonomic neuropathy (14 patients). Furthermore 8 patients suffered from an infection, one patient developed acute renal failure and one patient a deep vein thrombosis. HR was achieved in 78% of patients: CR in 9 (20%)and PR in 26 (58%) of45 evaluable patients, respectively. Organ response was observed in 5 patients at the end of the study (6 months after the end of treatment). In the historical M-dex group HR rate was lower (58%, p=0.06): CR in 6 (15%)andPR in 17(43%) of 40 evaluable patients. OS was significantly improved using L-M-dex (see figure 1, median OS not reached vs. 26 mo., p=0.03). There was also a trend for a better EFS in the L-M-dex group (see figure 2, median EFS 23 vs. 16 mo., p=0.06). Of note, 3 L-M-dex patients (6%) died within 3 months after start of chemotherapy compared to 10 patients (19%) in the M-dex-group. Conclusion This is the largest phase II trial usinglenalidomide, melphalan and dexamethason in newly diagnosed AL amyloidosis patients. Treatment was effective and feasible in this cohort of mostly elderlypatients. 78% of evaluable patients achieved a hematologic remission. The early death rate was low with 6% despite of inclusion of a high number of patients with advanced cardiac amyloidosis. Overall, toxicity was manageable in most patients. Further improvement of these results might be achieved by prolongation of therapy in patients who have responded to and tolerate this combination therapy well. Disclosures: Schonland: Celgene: Honoraria; Janssen: Honoraria. Off Label Use: lenalidomide in amyloidosis. Hegenbart:Janssen: Honoraria.

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Dose-Intensive Melphalan With Blood Stem-Cell Support for the Treatment of AL (Amyloid Light-Chain) Amyloidosis: Survival and Responses in 25 Patients

Blood ◽

10.1182/blood.v91.10.3662 ◽

1998 ◽

Vol 91 (10) ◽

pp. 3662-3670 ◽

Cited By ~ 247

Author(s):

Raymond L. Comenzo ◽

Evan Vosburgh ◽

Rodney H. Falk ◽

Vaishali Sanchorawala ◽

Johann Reisinger ◽

...

Keyword(s):

Plasma Cell ◽

Light Chain ◽

Performance Status ◽

Al Amyloidosis ◽

Organ Systems ◽

Plasma Cell Disorders ◽

Plasma Cell Disorder ◽

Amyloid Light Chain ◽

Al Amyloid ◽

Cell Disorder

Abstract AL (amyloid light-chain) amyloidosis is an uncommon plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure and death in a median of 13 months. Autologous stem-cell transplantation is effective therapy for multiple myeloma and therefore, we evaluated its efficacy for AL amyloidosis. Patients with adequate cardiac, pulmonary, and renal function had stem cells mobilized with granulocyte-colony stimulating factor and were treated with dose-intensive intravenous melphalan (200 mg/m2). Response to therapy was determined by survival and improvement of performance status, complete response or persistence of the clonal plasma cell disorder, and change in the function of organs involved with amyloid at baseline. We enrolled 25 patients with a median age of 48 years (range, 29-60), all of whom had biopsy-proven amyloidosis with clonal plasma cell disorders. Twenty-two (88%) were Southwest Oncology Group performance status 1 or 2 within a year of diagnosis, and 16 (64%) had received no prior therapy. Predominant amyloid-related organ involvement was cardiac (n = 8), renal (n = 7), hepatic (n = 6), neuropathic (n = 3), and lymphatic (n = 1). Fifteen patients had one or two organ systems involved, whereas 10 had three or more involved. With a median follow-up of 24 months (12-38), 17 of 25 patients (68%) are alive, and the median survival has not been reached. Thirteen of 21 patients (62%) evaluated 3 months posttransplant had complete responses of their clonal plasma cell disorders. Currently, two thirds of the surviving patients (11 of 17) have experienced improvements of amyloid-related organ involvement in all systems, whereas 4 of 17 have stable disease. The improvement in the median performance status of the 17 survivors at follow-up (0 [range, 0-3]) is statistically significant versus baseline (2 [range, 1-3]; P < .01). Significant negative prognostic factors with respect to overall survival include amyloid involvement of more than two major organ systems and predominant cardiac involvement. Three patients have experienced relapses of the clonal plasma cell disorder at 12 and 24 months. Dose-intensive therapy should currently be considered as the preferred therapy for patients with AL amyloidosis who meet functional criteria for autologous transplantation.

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Dose-Intensive Melphalan With Blood Stem-Cell Support for the Treatment of AL (Amyloid Light-Chain) Amyloidosis: Survival and Responses in 25 Patients

Blood ◽

10.1182/blood.v91.10.3662.3662_3662_3670 ◽

1998 ◽

Vol 91 (10) ◽

pp. 3662-3670 ◽

Cited By ~ 3

Author(s):

Raymond L. Comenzo ◽

Evan Vosburgh ◽

Rodney H. Falk ◽

Vaishali Sanchorawala ◽

Johann Reisinger ◽

...

Keyword(s):

Plasma Cell ◽

Light Chain ◽

Performance Status ◽

Al Amyloidosis ◽

Organ Systems ◽

Plasma Cell Disorders ◽

Plasma Cell Disorder ◽

Amyloid Light Chain ◽

Al Amyloid ◽

Cell Disorder

AL (amyloid light-chain) amyloidosis is an uncommon plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure and death in a median of 13 months. Autologous stem-cell transplantation is effective therapy for multiple myeloma and therefore, we evaluated its efficacy for AL amyloidosis. Patients with adequate cardiac, pulmonary, and renal function had stem cells mobilized with granulocyte-colony stimulating factor and were treated with dose-intensive intravenous melphalan (200 mg/m2). Response to therapy was determined by survival and improvement of performance status, complete response or persistence of the clonal plasma cell disorder, and change in the function of organs involved with amyloid at baseline. We enrolled 25 patients with a median age of 48 years (range, 29-60), all of whom had biopsy-proven amyloidosis with clonal plasma cell disorders. Twenty-two (88%) were Southwest Oncology Group performance status 1 or 2 within a year of diagnosis, and 16 (64%) had received no prior therapy. Predominant amyloid-related organ involvement was cardiac (n = 8), renal (n = 7), hepatic (n = 6), neuropathic (n = 3), and lymphatic (n = 1). Fifteen patients had one or two organ systems involved, whereas 10 had three or more involved. With a median follow-up of 24 months (12-38), 17 of 25 patients (68%) are alive, and the median survival has not been reached. Thirteen of 21 patients (62%) evaluated 3 months posttransplant had complete responses of their clonal plasma cell disorders. Currently, two thirds of the surviving patients (11 of 17) have experienced improvements of amyloid-related organ involvement in all systems, whereas 4 of 17 have stable disease. The improvement in the median performance status of the 17 survivors at follow-up (0 [range, 0-3]) is statistically significant versus baseline (2 [range, 1-3]; P < .01). Significant negative prognostic factors with respect to overall survival include amyloid involvement of more than two major organ systems and predominant cardiac involvement. Three patients have experienced relapses of the clonal plasma cell disorder at 12 and 24 months. Dose-intensive therapy should currently be considered as the preferred therapy for patients with AL amyloidosis who meet functional criteria for autologous transplantation.

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From light chain deposition to multiple myeloma – Case report and literature review

Portuguese Journal of Nephrology & Hypertension ◽

10.32932/pjnh.2021.01.104 ◽

2021 ◽

Vol 34 (4) ◽

Author(s):

Ana Domingos ◽

◽

Joana Vidinha ◽

Anabela Guedes ◽

Ana Macedo ◽

...

Keyword(s):

Multiple Myeloma ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Monoclonal Immunoglobulin ◽

Monoclonal Immunoglobulin Deposition Disease ◽

Deposition Disease ◽

Malignant Plasma Cell ◽

Plasma Cell Disorder ◽

Light Chain Deposition ◽

Cell Disorder

Monoclonal gammopathies consist of a broad spectrum of diseases, ranging from asymptomatic monoclonal gammopathy of undetermined significance to multiple myeloma (MM). Multiple myeloma is a malignant plasma cell disorder and accounts for 10% of all hematological malignancies and 1% of all malignancies. Differential diagnosis may be challenging, considering the variety of clinical entities with similar behavior. About 15‑20% of MM only secretes monoclonal light chains, called light chain MM, which is associated with poorer outcome. Two intermediate concepts were recently introduced, monoclonal gammopathy of renal significance (MGRS) and a wider concept of monoclonal gammopathy of clinical significance (MGCS). The former behaves as a clonal proliferative disorder with associated nephrotoxicity, but does not have the hematological criteria for MM, while MGCS expands this concept to other organs. A subtype of MGCS is monoclonal immunoglobulin deposition disease, a multisystemic disorder characterized by light or heavy chain deposition of monoclonal immunoglobulin in various organs and encompasses three clinical entities: Light‑Chain, Light‑ and Heavy‑Chain, and Heavy‑Chain Deposition Disease (LCDD, LHCDD and HCDD, respectively). We describe an unusual case of LCDD in which MM was subsequently considered although the proposed criteria are not met. We demonstrate the variability of clinical‑pathological presentation of LCDD, requiring a rapid decision‑making, particularly in terms of kidney and survival outcomes.

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The Serum Free Light Chain Ratio after One or Two Cycles of Treatment Is Highly Predictive of the Magnitude of Final Response in Patients Undergoing Initial Treatment for Multiple Myeloma.

Blood ◽

10.1182/blood.v106.11.3481.3481 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3481-3481

Author(s):

Hani Hassoun ◽

Lilian Reich ◽

Virginia M. Klimek ◽

Madhav Dhodapkar ◽

Adam Cohen ◽

...

Keyword(s):

Multiple Myeloma ◽

Complete Remission ◽

Light Chain ◽

Initial Therapy ◽

Free Light Chain ◽

Light Chains ◽

Al Amyloidosis ◽

Serum Free ◽

The Status ◽

Final Response

Abstract BACKGROUND: The serum free light chains assay (FLC) has recently become commercially available for use in the management of multiple myeloma. This assay is more sensitive for the detection of monoclonal light-chains than previously available tests and has therefore found many unique applications. It can detect two-thirds of non-secretory multiple myelomas that were previously missed by immunofixation; it permits a more sensitive detection of monoclonal FLCs in AL amyloidosis; and it may allow earlier identification of disease recurrence in multiple myeloma and amyloidosis patients after treatment. We have sought to examine the usefulness of this assay as an early predictor of final response in patients with symptomatic multiple myeloma undergoing initial therapy. METHODS: We have performed an analysis of FLC assay in forty-five patients who were enrolled in an IRB approved phase II clinical trial whose main objectives were to determine the efficacy and toxicity of the administration of doxorubicin and dexamethasone, followed by thalidomide and dexamethasone in patients with untreated multiple myeloma (ASH 2004). The response to treatment was assessed based on the EORTC consensus criteria. Using Fisher’s exact test, we have evaluated the association between the status of the FLC ratio after cycle one and cycle two (i.e. normalized or persistently abnormal) and the status of response at the completion of 5 cycles of treatment, in patients with an abnormal FLC ratio at baseline (normal range 0.26 – 1.65). RESULTS: Of the 42 patients evaluable for response, 37 had an abnormal free light chain ratio at baseline (i.e. < 0.26 or > 1.65). Normalization of the FLC ratio after cycle one or cycle two occurred in seven out of 15 patients who achieved near complete remission (nCR) or complete remission (CR), and only in one of 22 patients who achieved partial remission (PR), stable disease (SD), or progression of disease (POD). Among the eight patients who had normalization of the FLC ratio after one or two cycles of treatment, seven achieved nCR or CR and one achieved PR. Normalization of the FLC ratio after one or two cycles of treatment was significantly associated with the achievement of CR or nCR (p=0.003). CONCLUSION: Normalization of the free light chain ratio after the first or the second cycle of treatment is highly predictive of achievement of nCR or CR at the completion of treatment. If this observation is confirmed in larger studies and for other regimens, the assessment of the free light chain ratio after two cycles may become an important milestone in the decision making for patients with multiple myeloma undergoing initial therapy. Since the aim of therapy is to achieve nCR or CR, the addition of alternative drugs might be advisable at an early stage of treatment in patients whose free light chain ratio remains abnormal.

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

Blood ◽

10.1182/blood-2008-04-154484 ◽

2009 ◽

Vol 113 (7) ◽

pp. 1501-1503 ◽

Cited By ~ 6

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.

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