Cited by 233Multiple Myeloma Research and TreatmentsChronic Lymphocytic Leukemia ResearchLymphoma Diagnosis and Treatment

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Progression in Smoldering Myeloma Is Independently Determined by the Chromosomal Abnormalities del(17p), t(4;14), Gain 1q, Hyperdiploidy, and Tumor Load

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Neben, Kai, Jauch, Anna, Hielscher, Thomas, Hillengass, Jens, Lehners, Nicola, Seckinger, Anja, Granzow, Martin, Raab, Marc S., Ho, Anthony D., Goldschmidt, Hartmut, Hose, Dirk·2013·Journal of Clinical Oncology

DOI 10.1200/jco.2012.48.4923

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Abstract

Purpose: The aim of this study was to analyze chromosomal aberrations in terms of frequency and impact on time to progression in patients with smoldering multiple myeloma (SMM) on the background of clinical prognostic factors. Patients and Methods: The chromosomal abnormalities 1q21, 5p15/5q35, 9q34, 13q14.3, 15q22, 17p13, t(11;14)(q13;q32), and t(4;14)(p16.3;q32) were assessed in CD138-purified myeloma cells by interphase fluorescent in situ hybridization (iFISH) alongside clinical parameters in a consecutive series of 248 patients with SMM. Results: The high-risk aberrations in active myeloma (ie, del(17p13), t(4;14), and +1q21) present in 6.1%, 8.9%, and 29.8% of patients significantly confer adverse prognosis in SMM with hazard ratios (HRs) of 2.90 (95% CI, 1.56 to 5.40), 2.28 (95% CI, 1.33 to 3.91), and 1.66 (95% CI, 1.08 to 2.54), respectively. Contrary to the conditions in active myeloma, hyperdiploidy, present in 43.3% of patients, is an adverse prognostic factor (HR, 1.67; 95% CI, 1.10 to 2.54). Percentage of malignant bone marrow plasma cells assessed by iFISH and combination of M-protein and plasma cell infiltration as surrogates of tumor load significantly confer adverse prognosis with HRs of 4.37 (95% CI, 2.79 to 6.85) and 4.27 (95% CI, 2.77 to 6.56), respectively. In multivariate analysis, high-risk aberrations, hyperdiploidy, and surrogates of tumor load are independently prognostic. Conclusion: The high-risk chromosomal aberrations del(17p13), t(4;14), and +1q21 are adverse prognostic factors in SMM just as they are in active myeloma, independent of tumor mass. Hyperdiploidy is the first example for an adverse prognostic factor in SMM of opposite predictiveness in active myeloma. Risk association of chromosomal aberrations is not only a priori treatment dependent (predictive) but is also an intrinsic property of myeloma cells (prognostic).

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Authors: Neben, K., Jauch, A., Hielscher, T., Hillengass, J., Lehners, N., Seckinger, A., Granzow, M., Raab, M. S., Ho, A. D., Goldschmidt, H., & Hose, D.
Affiliations: German Cancer Research Center (DE)
ORCID: Neben, Kai
Jauch, Anna
Hielscher, Thomas
Hillengass, Jens
Seckinger, Anja
Raab, Marc S.
Ho, Anthony D.
Goldschmidt, Hartmut
Hose, Dirk
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2013-12-01
Volume: 31
Issue: 34
Pages: 4325-4332
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2012.48.4923
OpenAlex: W2126894260
Semantic Scholar: 3454ef568a1d73e48a414842f0c56b0cc223ddf6
Cited by: 233
References: 32
Citations by year: 2026: 3 · 2025: 12 · 2024: 17 · 2023: 16 · 2022: 13 · 2021: 24 · 2020: 23 · 2019: 13 · 2018: 20 · 2017: 21 · 2016: 18 · 2015: 26 · 2014: 25 · 2013: 2
FWCI: 16.86
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Funders: Deutsche Forschungsgemeinschaft (SFB TRR 79)
Topics: Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
Keywords: smoldering multiple myeloma, progression to multiple myeloma, chromosomal abnormalities, 17p deletion, hyperdiploidy, tumor burden, prognostic factors, time to progression, M protein, plasma cell infiltration
MeSH terms: Chromosome Deletion, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 4, Humans, Multiple Myeloma, Phenotype, Ploidies, Risk Factors, Translocation, Genetic, Multivariate Analysis, Proportional Hazards Models, In Situ Hybridization, Fluorescence, Disease Progression, Genetic Predisposition to Disease, Tumor Burden

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Progression in Smoldering Myeloma Is Independently Determined by the Chromosomal Abnormalities del(17p), t(4;14), Gain 1q, Hyperdiploidy, and Tumor Load

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