Chromosomal aberrations in 130 patients with multiple myeloma studied by interphase FISH: diagnostic and prognostic relevance

Schmidt‐Wolf, Ingo G.H.; Glasmacher, Axel; Hahn-Ast, Corinna; Juttner, Andrea; Schnurr, Theresia M.; Cremer, FW; Michel, Thomas; Goldschmidt, Hartmut; Busert, Barbara; Schubert, Regine; Schwanitz, Gesa

doi:10.1016/j.cancergencyto.2005.10.016

Cited by 28 publications

(22 citation statements)

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“…In our study, conventional cytogenetics detected chromosomal aberrations in 25% of our cohort of 68 MM patients, what is in line with results published by Christensen et al [8]. Analysis using interphase FISH combined with immunofluorescent labeling or immunomagnetic separation of plasma cells is known to have a higher sensitivity and finds chromosomal abnormalities in 86-98% of MM patients [9][10][11]. Using the technique of cIg-FISH for the detection of selected chromosomal abnormalities including del(13)(q14), del(17)(p13), gain 1q21, IgH rearrangements, t(11;14) translocation and t(4;14) translocation we have been able to detect at least one chromosomal alteration in 82% of our patients.…”

Section: Discussionsupporting

confidence: 92%

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confidence: 99%

“…In contrast, the technique of interphase fluorescent in situ hybridization (I-FISH) in combination with cytoplasm immunoglobulin staining or immunomagnetic separation of plasma cells enables detection of specific abnormalities in up to 86-98% of patients [9,10,11]. The most commonly encountered chromosomal aberrations Negative prognostic significance of two or more cytogenetic abnormalities in multiple myeloma patients treated with autologous stem cell transplantation (11;14), t(4;14), del(17)(p13) and gain 1q21.…”

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Negative prognostic significance of two or more cytogenetic abnormalities in multiple myeloma patients treated with autologous stem cell transplantation

Grešlíková

Zaoralová²,

Filková³

et al. 2010

neo

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Multiple myeloma (MM) is the second most common haematological malignancy. It is characterized by malignant transformation and clonal proliferation of B-lymphocytes with the accumulation of malignant plasma cells in the bone marrow. The incidence of MM increases with age. The average age at presentation is 62 years in men and 61 years in women [1]. Patients below 40 years of age represent less than 3% of all cases. For many years, conventional chemotherapy with combination of melphalan and prednisone was the standard treatment, resulting in overall survival (OS) of approximately 3 years [2]. Currently, high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation is recommended for patients below the age of 65 [3,4]. This treatment extends the OS to 4-5 years [5], with approximately 28% of patients surviving 5 or more years [6]. Despite this relative treatment success, MM remains an incurable disease. Many prognostic factors for MM have been identified. The presence of numerical and/or structural chromosomal aberrations is one of the most important indicators for the prognostic assessments.Due to low proliferation activity of MM cells, conventional cytogenetics detects chromosomal changes in as few as 26-40% of cases [7,8]. In contrast, the technique of interphase fluorescent in situ hybridization (I-FISH) in combination with cytoplasm immunoglobulin staining or immunomagnetic separation of plasma cells enables detection of specific abnormalities in up to 86-98% of patients [9,10,11] Received April 8, 2009Malignant plasma cells in multiple myeloma (MM) are frequently characterized by complex karyotypes and chromosome instability. These cytogenetic changes are considered important prognostic indicators in MM patients. We have studied samples from 68 patients with newly diagnosed MM who were treated with high-dose chemotherapy and autologous stem cell transplantation. G-banding revealed abnormal karyotypes in 14 of 55 patients (25%) who had informative conventional cytogenetics. The combination of cytoplasmic immunoglobulin light chain labeling and interphase fluorescent in situ hybridization (cIg-FISH) revealed the presence of genetic aberrations in 53 of 68 patients (78%). Chromosome 13 abnormalities were found in 33 patients (50%) and IgH rearrangements in 36 patients (56.25%). In IgH positive patients we performed subsequent examinations of IgH affecting translocations t(4;14) and t(11;14) and we found translocation t(11;14) in 8 patients (12.5%) and t(4;14) in 10 patients (15.5%). The occurrences of others chromosomal abnormalities with known prognostic impact in MM were as follows: del(17)(p13) was present in 5 patients (9.8%) and gain 1q21 in 14 patients (36%). Analysis of survival of patients with different cytogenetic abnormalities revealed shorter overall survival (OS) in patients with IgH rearrangements (p=0.020) and trend to shorter OS in patients with gain 1q21 (p=0.064), respectively. Remarkably, patients with two or more aberrations had significantly shorter overall surviva...

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Section: Discussionsupporting

confidence: 92%

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confidence: 99%

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confidence: 99%

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Negative prognostic significance of two or more cytogenetic abnormalities in multiple myeloma patients treated with autologous stem cell transplantation

Grešlíková

Zaoralová²,

Filková³

et al. 2010

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“…9,10 Chromosomal abnormalities Chromosome 13q deletion [del (13)] was analyzed by interphase FISH techniques on freshly purified bone marrow plasma cells as previously described. 13 …”

Section: Analyses Of Chimerismmentioning

confidence: 99%

Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo

Bruno

Rotta

Patriarca

et al. 2009

Blood

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IntroductionDespite remarkable recent advances in its treatment, multiple myeloma remains incurable. 1 Allografting is still regarded as the only potential cure on account of its well-documented graft-versusmyeloma effect observed in a subset of patients. [2][3][4][5] However, its use remains controversial especially in newly diagnosed patients.In the late 1990s, the introduction of reduced intensity/ nonmyeloablative conditionings greatly renewed the interest in allografting, in particular for diseases such as myeloma where the transplantation-related mortality (TRM) with conventional transplantation regimens had been unacceptably high. [5][6][7] Combining the cytoreductive effect of a high-dose melphalan-based autograft with the graft-versus-myeloma effects of a nonmyeloablative allograft reduced TRM even in elderly, medically unfit myeloma patients. 8,9 Our recent comparison between autografting and nonmyeloablative allografting showed that the latter resulted in longer overall survival (OS) and event-free survival (EFS) in newly diagnosed patients younger than 65 years. 10 Preliminary reports from other groups have confirmed our findings. 11,12 Here, we report on an extended experience consisting of 100 newly diagnosed myeloma patients enrolled in a prospective clinical trial (http://ClinicalTrial.gov; NCT-00702247) and treated with nonmyeloablative allografts as part of their first-line treatment at 15 Italian Bone Marrow Transplantation Units of the Gruppo Italiano Trapianti di Midollo Osseo (GITMO). Methods Patients and donorsFrom July 1999 to June 2005, 100 newly diagnosed myeloma patients younger than 65 years were enrolled in a prospective multicenter trial. Informed consent was obtained upon enrollment in accordance with the An Inside Blood analysis of this article appears at the front of this issue.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. Inclusion criteria included diagnosis of untreated Durie & Salmon stage IIA to IIIB multiple myeloma or stage I progressed to require therapy; age less than 65 years; Karnofsky performance status greater than 60%; and presence of an human leukocyte antigen (HLA)-identical sibling donor eligible for peripheral blood stem cell (PBSC) donation. Exclusion criteria included prior treatment for myeloma, abnormal cardiac function and chronic respiratory disease defined as systolic ejection fraction less than 35% and carbon monoxide diffusing capacity less than 40% of predicted or need of continuous supplemental oxygen, respectively; serum bilirubins greater than twice normal and alanine amino transferase (ALAT) and/or aspartate amino transferase (ASAT) greater than 4 times normal; poorly controlled hypertension; pregnancy; and seropositivity for HIV. Patients with active nonhematologic malignancies except nonmelanoma skin cancers or who were less than 5 years from the achievement of complete remissi...

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“…Chromosomal abnormalities of 14q32 are the most frequent chromosomal abnormalities, which have been observed in about 75% of patients with plasma cell myeloma and have been associated in the oncogenesis of MM [24] .…”

Section: Disscusionmentioning

confidence: 99%

Interphase Fluorescence in Situ Hybridization Analysis of Cytogenetic Abnormalities in Egyptian Patients with Plasma Cell Myeloma

Hashem¹,

Boshnak²

2016

jmscr

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Chromosomal aberrations in 130 patients with multiple myeloma studied by interphase FISH: diagnostic and prognostic relevance

Cited by 28 publications

References 22 publications

Negative prognostic significance of two or more cytogenetic abnormalities in multiple myeloma patients treated with autologous stem cell transplantation

Negative prognostic significance of two or more cytogenetic abnormalities in multiple myeloma patients treated with autologous stem cell transplantation

Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo

Interphase Fluorescence in Situ Hybridization Analysis of Cytogenetic Abnormalities in Egyptian Patients with Plasma Cell Myeloma

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