AL amyloidosis: The effect of fluorescent in situ hybridization abnormalities on organ involvement and survival

Ozga, Michael; Zhao, Qiuhong; Benson, Don M.; Elder, Patrick; Williams, Nita; Bumma, Naresh; Rosko, Ashley; Chaudhry, Maria; Khan, Abdullah; Devarakonda, Srinivas; Kahwash, Rami; Vallakati, Ajay; Campbell, Courtney; Parikh, Samir; Almaani, Salem; Prosek, Jason; Bittengle, Jordan; Pfund, Katherine; LoRusso, Samantha; Freimer, Miriam; Redder, Elyse; Efebera, Yvonne A.; Sharma, Nidhi

doi:10.1002/cam4.3683

Cited by 13 publications

(21 citation statements)

References 22 publications

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“…Another study conducted by Ozga et al described a broader definition of hyperdiploidy that included gains/ trisomies of 2 or more of any chromosome loci. In this study, 38% of patients harbored hyperdiploidy, which was confirmed to be associated with shorter PFS and OS in the multivariate analysis [17].…”

Section: Hyperdiploidysupporting

confidence: 73%

“…About 10-40% of AL patients cannot be detected to harbor any chromosome aberration by the MM's genetic probes. This patient group tends to have lower plasma cell burden, less severe cardiac involvement, longer progression-free survival (PFS) and overall survival (OS) [15][16][17]19], indicating that the absence of chromosome aberration in AL may be a favorable prognostic predictor of outcome.…”

Section: Normal Chromosome Profilementioning

confidence: 99%

“…The presence of del13q in MGUS is associated with a higher risk of progression to MM, while its prognostic effect in MM tends to be neutral [ 53 ]. In AL, monosomy 13/del 13q are the only chromosome abnormalities identified so far to have cardiac tropism and are associated with high NT-proBNP level [ 15 , 17 , 65 ]. They also correlate with plasmacytosis and a high dFLC level [ 15 , 17 ].…”

Section: Secondary Genetic Eventsmentioning

confidence: 99%

“…In AL, monosomy 13/del 13q are the only chromosome abnormalities identified so far to have cardiac tropism and are associated with high NT-proBNP level [ 15 , 17 , 65 ]. They also correlate with plasmacytosis and a high dFLC level [ 15 , 17 ]. However, no prognostic significance has been identified related to these genetic aberrations.…”

Section: Secondary Genetic Eventsmentioning

confidence: 99%

“…This review article will focus on the pathogenesis, clinical features, and prognostic impacts of different genetic Patients with AL also show a high frequency of chromosome instability like other plasma cell disorders. Data shows that 60-90% of AL patients harbor at least one chromosome abnormalities and about 50-70% of them have translocations involving the IgH locus on chromosome 14 [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications

2021

Exp Hematol Oncol

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Immunoglobulin light chain amyloidosis (AL) is an indolent plasma cell disorder characterized by free immunoglobulin light chain (FLC) misfolding and amyloid fibril deposition. The cytogenetic pattern of AL shows profound similarity with that of other plasma cell disorders but harbors distinct features. AL can be classified into two primary subtypes: non-hyperdiploidy and hyperdiploidy. Non-hyperdiploidy usually involves immunoglobulin heavy chain translocations, and t(11;14) is the hallmark of this disease. T(11;14) is associated with low plasma cell count but high FLC level and displays distinct response outcomes to different treatment modalities. Hyperdiploidy is associated with plasmacytosis and subclone formation, and it generally confers a neutral or inferior prognostic outcome. Other chromosome abnormalities and driver gene mutations are considered as secondary cytogenetic aberrations that occur during disease evolution. These genetic aberrations contribute to the proliferation of plasma cells, which secrete excess FLC for amyloid deposition. Other genetic factors, such as specific usage of immunoglobulin light chain germline genes and light chain somatic mutations, also play an essential role in amyloid fibril deposition in AL. This paper will propose a framework of AL classification based on genetic aberrations and discuss the amyloid formation of AL from a genetic aspect.

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Section: Hyperdiploidysupporting

confidence: 73%

Section: Normal Chromosome Profilementioning

confidence: 99%

Section: Secondary Genetic Eventsmentioning

confidence: 99%

Section: Secondary Genetic Eventsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications

2021

Exp Hematol Oncol

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Immunoglobulin light chain amyloidosis: 2022 update on diagnosis, prognosis, and treatment

Gertz

2022

American J Hematol

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Disease overview Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and “atypical smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS).” Diagnosis Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required for the diagnosis of AL amyloidosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy. Prognosis N‐terminal pro–brain natriuretic peptide (NT‐proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 73, 35, 15, and 5 months. Therapy All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first‐line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a complete response (CR). In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine. Future challenges Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end‐stage organ failure. Trials of antibodies to catabolize deposited fibrils are underway.

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Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment

Gertz

2023

American J Hematol

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Disease OverviewImmunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and “atypical smoldering multiple myeloma or MGUS.”DiagnosisTissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required for the diagnosis of AL amyloidosis. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy.PrognosisN‐terminal pro–brain natriuretic peptide (NT‐proBNP or BNP), serum troponin T(or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5‐year survivals are 82%, 62%, 34%, and 20%, respectively.TherapyAll patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first‐line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥VGPR. In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine.Future ChallengesDelayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end‐stage organ failure. Trials of antibodies to deplete deposited fibrils are underway.

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AL amyloidosis: The effect of fluorescent in situ hybridization abnormalities on organ involvement and survival

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 13 publications

References 22 publications

Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications

Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications

Immunoglobulin light chain amyloidosis: 2022 update on diagnosis, prognosis, and treatment

Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment

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