Role of Conventional Karyotyping in Multiple Myeloma in the Era of Modern Treatment and FISH Analysis

Soekojo, Cinnie Yentia; Wang, Guo-miao; Chen, Yunxin; Casan, Joshua; Wolyncewicz, Grace; Lin, Adeline; Poon, Li Mei; Mel, Sanjay de; Koh, Liang Piu; Tan, Lip Kun; Ooi, Melissa; Nagarajan, Chandramouli; Liu, Yang; Lai, Yue‐Yun; Huang, Xiao‐Jun; Spencer, Andrew; Gopalakrishnan, Sathish; Lu, Jin; Chng, Wee Joo

doi:10.1016/j.clml.2019.04.011

Cited by 6 publications

(5 citation statements)

References 13 publications

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“…The three prognostic factors that affect survival after first relapse identified in our study have their unique clinical relevance. Non-hyperdiploid karyotype at diagnosis may identify a more proliferative underlying myeloma clone and has recently demonstrated its consistency with FISH to predict high-risk patients at diagnosis [ 21 ]. Although not informative in the majority of patients, in those with abnormal non-hyperdiploid karyotype, this clearly identifies a subgroup of myeloma with aggressive biology that is associated with difficult salvage and poor post-relapse survival, even in the modern era with novel therapies [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Natural History and Prognostic Factors at First Relapse in Multiple Myeloma

Wang

Soekojo

Mel

et al. 2020

Cancers

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The prognosis of multiple myeloma has considerably improved due to the introduction of novel agents in the upfront setting. However, the great majority of patients ultimately relapse, and choosing a salvage treatment at first relapse remains challenging. The natural history of first relapsed disease in the current era is also not well described. We retrospectively studied 300 patients with first relapsed myeloma seen between 2004 and 2019 from two institutes in Singapore. The median duration from diagnosis to first relapse was 22.7 months (1.1–97.0 months). Most patients received novel agent-based induction therapy, and 41.3% underwent autologous stem cell transplant. A very good partial response (VGPR) or better was achieved in 48.6%. Regarding first relapse, 50.5% were symptomatic and 19.0% received newer agent-containing regimens. Nearly a third of patients (31.7%) had a VGPR or better response. The median progression free and overall survival from first relapse was 12.0 and 44.8 months, respectively. Based on a randomized sample splitting, we first identified non-hyperdiploid karyotype at diagnosis, clinical relapse, and treatment sequence as impacting survival independently from a testing cohort, and we then further demonstrated their significance in a validation cohort. This study provides a real-world picture of first relapsed myeloma and highlights the prognostic importance of the treatment sequence.

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Section: Discussionmentioning

confidence: 99%

Natural History and Prognostic Factors at First Relapse in Multiple Myeloma

Wang

Soekojo

Mel

et al. 2020

Cancers

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“…used conventional karyotyping to evaluate HR patients when FISH analysis was unavailable; this study showed patients with non-hyperdiploid myeloma had the worst outcomes which led to a worse OS in stage II R-ISS patients. 15 The loss of sex chromosomes in males and females is known to be related to aging. However, the loss of the Y chromosome in MM leads to genomic instability.…”

Section: Discussionmentioning

confidence: 99%

A diagnostic approach to detect cytogenetic heterogeneity and its prognostic significance in multiple myeloma

Kalal

Meenakshi²,

Shetty

et al. 2023

Journal of Taibah University Medical Sciences

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“…Conventional karyotyping studies in MM have been able to detect only 20–30% cells with abnormal karyotypes due to low proliferative index of G0 plasma cells in which cryptic translocations/insertions like t(4;14), t(14;16) were missed [ Sawyer et al, 1998 ; Chang et al, 2004 ]. On the other hand, karyotyping gives a global view of most of the known and unknown aberrations [ Sawyer et al, 1998 , 2014 ; Chang et al, 2004 ; Soekojo et al, 2019 ]. We could detect copy number changes in 1q along with translocation/insertion to multiple chromosomes, which cannot be detected by FISH.…”

Section: Discussionmentioning

confidence: 99%

Cytogenetic Abnormalities in Multiple Myeloma: Incidence, Prognostic Significance, and Geographic Heterogeneity in Indian and Western Populations

Amare¹,

Khasnis²,

Hande³

et al. 2022

Cytogenet Genome Res

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Multiple Myeloma(MM) is genetically complex and heterogeneous neoplasm in which cytogenetics is major genetic factor which plays an important role in the risk stratification of disease. High risk MM based upon cytogenetic classification includes primary IGH translocations t(4;14), t(14;16), t(14;20), and secondary progressive aberrations such as gain/Amp(1q) , 1p deletion , del(17p) & hypodiploidy. Several studies have proved that interphase FISH can efficiently detect primary as well as secondary cryptic aberrations very efficiently in lowest 5%- 10% abnormal plasma cells population. Present large scale study was undertaken to evaluate the incidence of cytogenetic abnormalities , to analyse the correlation of conventional karyotyping with FISH and to seek the geographic heterogeinity in the incidence of primary as well as secondary aberrations in our Indian vs Western population. We conducted prospective studies of 1104 patients consecutively referred from the primary, secondary and tertiary oncology centres from all over India. Interphase FISH was performed on isolated plasma cells. karyotype analysis was done as per ISCN, 2016,2020. In present large scale studies from India, FISH could detect cytogenetic abnormalities in 67.6% cases with an incidence of 59% non-hyperdiploidy(NHD). The incidence of IGH translocation was 26% vs literature frequency of 40%-50% which was mainly affected by low incidence 6% of t(11;14) in contrast to 15-20% in other series. Additionally, the association of secondary progressive aberrations in hyperdiploid (HD)group than non-hyperdiploid group in our patients is not a common finding . A biallelic inactivation of TP53 as an ultra-high risk factor was detected in old-aged patients. These observations disclose the novel findings and strongly indicate the racial disparity which leads to geographic heterogeneity. In contrast to FISH, conventional karyotyping could detect MM-related aberrations in 50% cases , of which 44% revealed highly complex karyotype with common aberrations of chromosome 1q. Overall FISH was found to be novel , easy approach with high success rate and capability of detection of all cytogenetic abnormalities that add valid information for the risk stratification of disease which in future in combination with mutation profile and Gene expression profile will help in further refinement of disease & identification of actionable targets.

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Role of Conventional Karyotyping in Multiple Myeloma in the Era of Modern Treatment and FISH Analysis

Cited by 6 publications

References 13 publications

Natural History and Prognostic Factors at First Relapse in Multiple Myeloma

Natural History and Prognostic Factors at First Relapse in Multiple Myeloma

A diagnostic approach to detect cytogenetic heterogeneity and its prognostic significance in multiple myeloma

Cytogenetic Abnormalities in Multiple Myeloma: Incidence, Prognostic Significance, and Geographic Heterogeneity in Indian and Western Populations

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