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Additional-structural-chromosomal aberrations are associated with inferior clinical outcome in patients with

Adrian A Carballo-Zarate¹, L Jeffrey Medeiros¹, Lianghua Fang^1,2

¹Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc

|March 11, 2017

Abstract:

Multiple myeloma is cytogenetically heterogeneous and a hyperdiploid karyotype is considered currently to have standard risk. In this study, we investigated the clinical impact of additional-structural-chromosomal aberrations assessed by chromosome analysis in 284 patients with a hyperdiploid karyotype that were subdivided into four groups based on the complexity of additional-structural-chromosomal aberrations: group 1, no additional-structural-chromosomal aberrations (n=35); group 2, one additional-structural-chromosomal aberration (n=46); group 3, two additional-structural-chromosomal aberrations (n=39); group 4, ≥three additional-structural-chromosomal aberrations (n=164). Clinicopathological data among these groups showed no differences, except patients in group 1 had higher hemoglobin (P=0.031) and albumin (P=0.045) levels. The median follow-up was 55 months (range, 3-221). The median overall survival of patients in groups 1-4 was negatively correlated with the number of the additional-structural-chromosomal aberrations: 98, 76, 61, and 48 months, respectively (P<0.0001). In group 4, CKS1B gain, RB1, or TP53 deletions had no additional impact on overall survival; however, trisomy 3 or 15 conferred a much better overall survival, and monosomy 13 and 14 predicted a worse outcome. In addition, the overall survival of patients in groups 3 and 4 was similar to a subset of high-risk multiple myeloma cases (n=21) (P=0.387). About 192 (67.6%) patients who received stem cell transplantation did not show improved overall survival compared with non-stem cell transplantation patients (n=92; P=0.142) overall; however, they did show significantly improved overall survival in patients with refractory disease in group 4 (P=0.0084). Multivariate analysis showed that two or more additional-structural-chromosomal aberrations (P<0.0001), stages (P=0.02 and P=0.002) and relapsed disease (P=0.009) negatively impacted the overall survival. We conclude that hyperdiploid karyotypes in multiple myeloma are associated with additional-structural-chromosomal aberrations and a greater number of additional-structural-chromosomal aberrations predicts poorer clinical outcome. A hyperdiploid karyotype with ≥2 additional-structural-chromosomal aberrations at chromosomal level should be considered an independent high-risk factor.

Insights

Multiple myeloma with hyperdiploid karyotypes can have varying risks. More additional-structural-chromosomal aberrations in these myeloma patients predict poorer outcomes, identifying a new high-risk factor.

Area of Science:

Hematology
Cytogenetics
Oncology

Background:

Multiple myeloma exhibits cytogenetic heterogeneity.
Hyperdiploid karyotypes are typically associated with standard risk in multiple myeloma.
The prognostic significance of additional-structural-chromosomal aberrations in hyperdiploid multiple myeloma requires further investigation.

Purpose of the Study:

To investigate the clinical impact of additional-structural-chromosomal aberrations in patients with hyperdiploid multiple myeloma.
To correlate the number of aberrations with overall survival and clinicopathological features.
To identify independent prognostic factors for multiple myeloma outcomes.

Main Methods:

Chromosome analysis was performed on 284 multiple myeloma patients with hyperdiploid karyotypes.
Patients were stratified into four groups based on the number of additional-structural-chromosomal aberrations.
Overall survival and clinicopathological data were analyzed using univariate and multivariate methods.

Main Results:

Overall survival was negatively correlated with the number of additional-structural-chromosomal aberrations (98, 76, 61, and 48 months for 0, 1, 2, and ≥3 aberrations, respectively).
Patients with two or more aberrations showed outcomes similar to high-risk multiple myeloma.
Multivariate analysis identified ≥2 aberrations, advanced stages, and relapsed disease as negative prognostic factors.

Conclusions:

Hyperdiploid karyotypes in multiple myeloma are frequently associated with additional-structural-chromosomal aberrations.
An increasing number of these aberrations predicts a poorer clinical outcome.
A hyperdiploid karyotype with ≥2 additional-structural-chromosomal aberrations should be considered an independent high-risk factor in multiple myeloma.

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