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.

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 ◽  
Bone Marrow ◽  
Light Chain ◽  
Clinical Characteristics ◽  
Al Amyloidosis ◽  
Term Survival ◽  
Bone Marrow Biopsies ◽  
Poor Prognostic Factor ◽  
Light Chain Amyloidosis ◽  
Amyloid Light Chain

Abstract Background Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of multiple myeloma with AL amyloidosis are not particularly clear. Methods Patients with 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 patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP ≧ 1000 pg/ml (P = 0.001), ALP > 187.5 IU/L (P = 0.002) and ALB < 35 g/L (P = 0.001), but lower incidence of HB < 85 g/L (P = 0.031), hypercalcemia > 2.65 mmol/L (P = 0.008), bone destruction more than three (P < 0.001), bone marrow plasma cell ratio ≧ 30% (P < 0.001) and worse D-S stage (P < 0.001). Multiple myeloma was more often complicated by λ-type AL amyloidosis than κ-type AL amyloidosis. However, further comparison found that multiple myeloma with κ-type AL amyloidosis had higher incidence of ALP > 187.5 IU/L (P = 0.001) and renal insufficiency (P = 0.001) along with worse D-S stage (P = 0.003) than multiple myeloma with λ-type AL amyloidosis. Renal biopsies of many patients suggested AL amyloidosis, but their bone marrow biopsies or subcutaneous abdominal fat pad aspirates results were negative. The existence of AL amyloidosis especially the heart involvement was related to shorter long-term survival of multiple myeloma according to univariate analysis. Cox regression model for overall survival detected the presence of AL amyloidosis in multiple myeloma having independent prognostic significance (RR = 4.52, P = 0.049). Conclusions Patients with multiple myeloma accompanied by AL amyloidosis have milder target organ damage and lower tumor burden. The incidence of AL amyloidosis in κ-type multiple myeloma is lower but more severe than λ-type multiple myeloma. Renal biopsy can help to identify patients with AL amyloidosis. AL amyloidosis is an independent poor prognostic factor for multiple myeloma is mainly because involvements of important organs especially the heart.

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.

scholarly journals Prognostic value of the albumin–globulin ratio and albumin–globulin score in patients with multiple myeloma

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199773
Author(s):  
Ying Cai ◽  
Yu Zhao ◽  
Qiuxin Dai ◽  
Maozhong Xu ◽  
Xin Xu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Value ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objective The albumin–globulin ratio (AGR) has been identified as a promising prognostic predictor of mortality in patients with hematological malignancies. This study investigated the prognostic significance of AGR in patients with multiple myeloma. Methods Two hundred patients diagnosed with multiple myeloma from January 2010 to October 2018 were retrospectively analyzed and followed up until December 2019. Kaplan–Meier curves and multivariate Cox regression analysis were applied to detect the prognostic value of AGR. Results The median follow-up period was 36 months. The optimal cutoff of AGR was 1.16 according to receiver operating characteristic curve analysis. High AGR was significantly correlated with better overall survival (OS) and progression-free survival (PFS). Multivariate analysis revealed that low AGR was an independent prognostic factor for worse OS (hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.15–2.94) and PFS (HR = 1.53, 95% CI = 1.09–2.17). Conclusions AGR may represent a potential prognostic biomarker in patients with multiple myeloma. Mini Abstract: We demonstrated that high AGR was associated with a favorable overall survival and progression-free survival in patients with multiple myeloma.

scholarly journals Splenic rupture secondary to amyloid light-chain (AL) amyloidosis associated with multiple myeloma

2019 ◽  
Vol 2019 (3) ◽  
Author(s):  
Jarrod Buzalewski ◽  
Matthew Fisher ◽  
Ryan Rambaran ◽  
Richard Lopez
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Splenic Rupture ◽  
Al Amyloidosis ◽  
Amyloid Light Chain

scholarly journals Myeloma coexisting with jejunal light chain amyloidosis

2020 ◽  
Vol 8 (10) ◽  
pp. 3738
Author(s):  
Aishwarya K. Marimuthu ◽  
Purnima Ramkumar ◽  
Mohammed S. Abdulsalam ◽  
Prabu Pandurangan ◽  
Jainudeen Khalander Abdul Jameel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Histopathological Examination ◽  
Resected Specimen ◽  
Al Amyloidosis ◽  
Proximal Jejunum ◽  
Abdominal Symptoms ◽  
Blood Clots ◽  
Initial Improvement ◽  
Amyloid Light Chain

Amyloid Light chain (AL) amyloidosis is a rare disease, which is seen in approximately one-tenth of patients with multiple myeloma. We report a 52 years old male, who presented with complaints of anorexia and weight loss. He was diagnosed to have multiple myeloma-international staging score (ISS) Stage 3 and was started on VTD (Bortezomib, Thalidomide, and Dexamethasone) chemotherapy. Within 2 weeks of therapy, he had abdominal symptoms like abdominal pain, loose stools, vomiting and hematochezia. Imaging showed dilated proximal bowel loops with fluid filled contents and prominent vessels in rectum. Emergency surgical exploration revealed thickened proximal jejunum with blood clots in the lumen. Resection of proximal jejunum was done. Histopathological examination of resected specimen was suggestive of AL amyloidosis. Post-surgical resection of jejunum, patient had initial improvement followed by deterioration. He was discharged against medical advice as per relative’s request. Hence an index of clinical suspicion of amyloidosis must been present in all Multiple myeloma patients.

scholarly journals IMPDH2 and HPRT expression and a prognostic significance in preoperative and postoperative patients with osteosarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Parunya Chaiyawat ◽  
Areerak Phanphaisarn ◽  
Nutnicha Sirikaew ◽  
Jeerawan Klangjorhor ◽  
Viraporn Thepbundit ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Drug Repurposing ◽  
Survival Times ◽  
Metabolizing Enzymes ◽  
Hypoxanthine Guanine Phosphoribosyltransferase ◽  
High Grade Osteosarcoma ◽  
Enneking Stage

AbstractOsteosarcoma is one of the most aggressive bone tumors in children and adolescents. Development of effective therapeutic options is still lacking due to the complexity of the genomic background. In previous work, we applied a proteomics-guided drug repurposing to explore potential treatments for osteosarcoma. Our follow-up study revealed an FDA-approved immunosuppressant drug, mycophenolate mofetil (MMF) targeting inosine-5′-phosphate dehydrogenase (IMPDH) enzymes, has an anti-tumor effect that appeared promising for further investigation and clinical trials. Profiling of IMPDH2 and hypoxanthine–guanine phosphoribosyltransferase (HPRT), key purine-metabolizing enzymes, could deepen understanding of the importance of purine metabolism in osteosarcoma and provide evidence for expanded use of MMF in the clinic. In the present study, we investigated levels of IMPDH2, and HPRT in biopsy of 127 cases and post-chemotherapy tissues in 20 cases of high-grade osteosarcoma patients using immunohistochemical (IHC) analysis. Cox regression analyses were performed to determine prognostic significance of all enzymes. The results indicated that low levels of HPRT were significantly associated with a high Enneking stage (P = 0.023) and metastatic status (P = 0.024). Univariate and multivariate analyses revealed that patients with low HPRT expression have shorter overall survival times [HR 1.70 (1.01–2.84), P = 0.044]. Furthermore, high IMPDH2/HPRT ratios were similarly associated with shorter overall survival times [HR 1.67 (1.02–2.72), P = 0.039]. Levels of the enzymes were also examined in post-chemotherapy tissues. The results showed that high IMPDH2 expression was associated with shorter metastasis-free survival [HR 7.42 (1.22–45.06), P = 0.030]. These results suggest a prognostic value of expression patterns of purine-metabolizing enzymes for the pre- and post-chemotherapy period of osteosarcoma treatment.

Light chain multiple myeloma with cutaneous AL amyloidosis

2008 ◽  
Vol 6 (9) ◽  
pp. 744-745 ◽  
Author(s):  
Maria Rita Becker ◽  
Rainer Rompel ◽  
Jörg Plum ◽  
Timo Gaiser
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Al Amyloidosis

scholarly journals High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis

Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 827-832 ◽  
Author(s):  
Frits van Rhee ◽  
Vanessa Bolejack ◽  
Klaus Hollmig ◽  
Mauricio Pineda-Roman ◽  
Elias Anaissie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Prognostic Significance ◽  
Complete Response ◽  
High Serum ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Rapid Reduction ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Serum-free light chain (SFLC) levels are useful for diagnosing nonsecretory myeloma and monitoring response in light-chain–only disease, especially in the presence of renal failure. As part of a tandem autotransplantation trial for newly diagnosed multiple myeloma, SFLC levels were measured at baseline, within 7 days of starting the first cycle, and before both the second induction cycle and the first transplantation. SFLC baseline levels higher than 75 mg/dL (top tertile) identified 33% of 301 patients with higher near-complete response rate (n-CR) to induction therapy (37% vs 20%, P = .002) yet inferior 24-month overall survival (OS: 76% vs 91%, P < .001) and event-free survival (EFS: 73% vs 90%, P < .001), retaining independent prognostic significance for both EFS (HR = 2.40, P = .008) and OS (HR = 2.43, P = .016). Baseline SFLC higher than 75 mg/dL was associated with light-chain–only secretion (P < .001), creatinine level 176.8 μM (2 mg/dL) or higher (P < .001), beta-2-microglobulin 297.5 nM/L (3.5 mg/L) or higher (P < .001), lactate dehydrogenase 190 U/L or higher (P < .001), and bone marrow plasmacytosis higher than 30% (P = .003). Additional independent adverse implications were conferred by top-tertile SFLC reductions before cycle 2 (OS: HR = 2.97, P = .003; EFS: HR = 2.56, P = .003) and before transplantation (OS: HR = 3.31, P = .001; EFS: HR = 2.65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline—reflecting more aggressive disease—and steeper reductions after therapy identified patients with inferior survival.

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