Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2

Abstract A panel of members of the 2009 International Myeloma Workshop developed guidelines for risk stratification in multiple myeloma. The purpose of risk stratification is not to decide time of therapy but to prognosticate. There is general consensus that risk stratification is applicable to newly diagnosed patients; however, some genetic abnormalities characteristic of poor outcome at diagnosis may suggest poor outcome if only detected at the time of relapse. Thus, in good-risk patients, it is necessary to evaluate for high-risk features at relapse. Although detection of any cytogenetic abnormality is considered to suggest higher-risk disease, the specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4;14) and del17p, and detection by fluorescence in situ hybridization of t(4;14), t(14;16), and del17p. Detection of 13q deletion by fluorescence in situ hybridization only, in absence of other abnormalities, is not considered a high-risk feature. High serum β2-microglobulin level and International Staging System stages II and III, incorporating high β2-microglobulin and low albumin, are considered to predict higher risk disease. There was a consensus that the high-risk features will change in the future, with introduction of other new agents or possibly new combinations.

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Plasma Cell Enrichment Enhances Detection of High-Risk Cytogenomic Abnormalities by Fluorescence In Situ Hybridization and Improves Risk Stratification of Patients With Plasma Cell Neoplasms

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2012-0209-oa ◽

2013 ◽

Vol 137 (5) ◽

pp. 625-631 ◽

Cited By ~ 15

Author(s):

Gary Lu ◽

Ramya Muddasani ◽

Robert Z. Orlowski ◽

Lynne V. Abruzzo ◽

Muzaffar H. Qazilbash ◽

...

Keyword(s):

In Situ Hybridization ◽

High Risk ◽

Risk Stratification ◽

Fluorescence In Situ Hybridization ◽

Plasma Cell ◽

Plasma Cells ◽

Cell Enrichment ◽

Plasma Cell Neoplasms

Context.—Methods for plasma cell enrichment of bone marrow (BM) specimens can increase the sensitivity of fluorescence in situ hybridization (FISH) for detecting cytogenomic abnormalities. There are no published reports using these methods to evaluate high-risk cytogenomic abnormalities in patients with plasma cell neoplasms (PCNs) after therapy. Objective.—To evaluate the utility of plasma cell enrichment combined with FISH for detection of high-risk cytogenomic abnormalities in patients with PCNs after therapy. Design.—Twenty-eight patients with PCNs, of whom 22 received treatment, were included in this study. Plasma cells were enriched in BM aspirates by using a magnetic cell-sorting procedure to select CD138+ cells. Probes were chosen to assess for del(17p13/TP53), del(13q14/RB1), 1q21/CKS1B gain, IgH/FGFR3, and IgH/MAF. Clinicopathologic data were collected during clinical follow-up after plasma cell enrichment. Results.—Plasma cells in nonenriched BM specimens ranged from 1% to 28% (median, 8%) compared with 28% to 96% (median, 73%) in enriched BM specimens (P < .001). In a subset of treated patients in clinical remission, FISH detected high-risk cytogenomic abnormalities only in plasma cell–enriched samples. This approach also detected abnormalities in cases of solitary plasmacytoma and monoclonal gammopathy of undetermined significance. Conclusions.—Plasma cell enrichment of BM specimens increases FISH sensitivity for detecting high-risk cytogenomic abnormalities, particularly in treated patients, and these results, in combination with clinical follow-up data, can be of value to improve risk stratification and patient management.

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The role of fluorescence in situ hybridization and gene expression profiling in myeloma risk stratification

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh11s2084h ◽

2011 ◽

Vol 139 (suppl. 2) ◽

pp. 84-89 ◽

Cited By ~ 1

Author(s):

Dirk Hose ◽

Anja Seckinger ◽

Anna Jauch ◽

Thierry Reme ◽

Jerome Moreaux ◽

...

Keyword(s):

Gene Expression ◽

Risk Assessment ◽

Multiple Myeloma ◽

Prognostic Factors ◽

In Situ Hybridization ◽

High Risk ◽

Risk Stratification ◽

Gene Expression Profiling ◽

Expression Profiling

Multiple myeloma patients? survival under treatment varies from a few months to more than 15 years. Clinical prognostic factors, especially beta2-microglobulin (B2M) and the international staging system (ISS), allow risk assessment to a certain extent, but do not identify patients at very high risk. As malignant plasma cells are characterized by a variety of chromosomal aberrations and changes in gene expression, a molecular characterization of CD138-purified myeloma cells by interphase fluorescence in situ hybridization (iFISH) and gene expression profiling (GEP) can be used for improved risk assessment. iFISH allows a risk stratification with presence of a translocation t(4;14) and/or deletion of 17p13 being the best documented adverse prognostic factors. A deletion of 13q14 is no longer considered to define adverse risk. Patients harbouring a t(4;14) seems to benefit from a bortezomib- or lenalidomide containing regimen, whereas patients with deletion 17p13 seem only to benefit from a high dose therapy approach using long term bortezomib (in induction and maintenance) and autologous tandem-transplantation as used in the GMMG-HD4 trial, or the total therapy 3 concept. Gene expression profiling allows the assessment of high risk scores (IFM, UAMS), remaining prognostic despite treatment with novel agents, and prognostic surrogates of biological factors (e.g. proliferation) and (prognostic) target gene expression (e.g. Aurora-kinase A). Thus, assessment of B2M and ISS-stage, iFISH, and GEP is considered extended routine diagnostics in therapy requiring multiple myeloma patients for risk assessment and, even now, to a certain extent selection of treatment.

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Pattern of Cytogenetic Abnormality by Fluorescence in Situ Hybridization (FISH) in Multiple Myeloma Patients in a Tertiary Hospital

Annals of International medical and Dental Research ◽

10.53339/aimdr.2022.8.1.29 ◽

2022 ◽

Vol 8 (1) ◽

pp. 212-224

Author(s):

Alamgir Ahmed

Keyword(s):

Multiple Myeloma ◽

In Situ Hybridization ◽

Risk Stratification ◽

Fluorescence In Situ Hybridization ◽

Prognostic Significance ◽

Staging System ◽

Cytogenetic Abnormality ◽

Survival Duration ◽

Female Ratio

Background: Multiple myeloma is a plasma cell neoplasm with acquired genetic abnormalities of clinical and prognostic importance, with survival duration ranging from a few months to more than 10 years. Cytogenetic abnormalities (CA) detected by fluorescence in situ hybridization (FISH) are of major prognostic significance since e.g. patients with del(17p), t(4;14) or gain 1q21 show dismal outcome. Objective: To evaluate the cytogenetic patterns by fluorescence in situ hybridization (FISH) of clinically diagnosed cases of multiple myeloma.Methods:This cross-sectional study was conducted in Department of Haematology, Dhaka Medical College Hospital, Dhaka, from January 2018 to December 2018. A total number of 30 patients with multiple myeloma were analyzed cytogenetically by interphase fluorescence in situ hybridization (iFISH). The collected data were analyzed by using the Statistical Package for Social Science (SPSS-24) for windows version 10.0.Results:Out of 30 diagnosed Multiple Myeloma cases the mean age was 56.37±10.38 years and male to female ratio was almost 3:1. Sixteen (56.7%) of 30 patients. Among 30 cases of 8 cases were thyrogenicity positive of 7(23.3%) patients was detected del 13q positive. Isolated del 13q was found in 4 cases. 2 cases were found coexistence of del 13q and del 17p positive ;1 case was found coexistence of del 13q and t(4;14) positive and rest of 1 case had del 17 p positive. There was no detectable t (11; 14) and t(14;16) in any of 30 cases.Conclusion:FISH panel for Multiple Myeloma including del (13q); t(11;14); t(4;14), del(17p), t(14;16) is very important molecular test for the prognosis , risk stratification, treatment modality of the patient. On the basis of cytogenetic abnormality Multiple Myeloma risk stratification is modified now a day. This Revised International Staging system R-ISS is a simple and powerful prognostic staging system.

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