An abnormal nonhyperdiploid karyotype is a significant adverse prognostic factor for multiple myeloma in the bortezomib era

Abstract

Multiple myeloma is clinically heterogeneous and risk stratification is vital for prognostication and informing treatment decisions. As bortezomib is able to overcome several high-risk features of myeloma, the validity of conventional risk-stratification and prognostication systems needs to be reevaluated. We study the survival data of 261 previously untreated myeloma patients managed at our institution, where bortezomib became available from 2004 for the treatment of relapse disease. Patient and disease characteristics, and survival data were evaluated overall, and with respect to bortezomib exposure. Overall, the international staging system (ISS), metaphase karyotyping and interphase fluorescence in situ hybridization (FISH) were discerning of survival outcomes, where the median for the entire cohort was 5.2 years. However, when stratified by bortezomib exposure, only metaphase karyotyping was still discriminating of long-term prognosis. The presence of an abnormal nonhyperdiploid karyotype overrides all other clinical and laboratory parameters in predicting for a worse outcome on multivariate analysis (median survival 2.6 years, P 5 0.001), suggesting that bortezomib used at relapse is better able to overcome adverse risk related to high tumor burden (as measured by the ISS) than adverse cytogenetics on conventional karyotyping. Metaphase karyotyping provides additional prognostic information on tumor kinetics where the presence of a normal diploid karyotype in the absence of any high-risk FISH markers correlated with superior survival and could act as a surrogate for lower plasma cell proliferation. Am. J. Hematol. 85:752-756, 2010. V

Amplification of 1q21 and Other Abnormalities in Multiple Myeloma Patients from a Tertiary Hospital in Singapore

“…This is in concordance with previous publications [16,20,23]. The finding is consistent with reports that alterations of RB1 are early events in multiple myeloma.…”

“…Much effort has therefore been made to further delineate MM patients according to their response to treatment, in particular the grouping of patients into the poor prognostic NH group and the better prognostic H group [15,16] and the ISS staging based on serum b 2 M levels [17]. Furthermore, specific chromosomal abnormalities have been determined to portend an unfavorable prognosis.…”

Evaluation of chromosomal abnormalities by cIg-FISH and association with proliferative and apoptotic indexes in multiple myeloma

“…Although these abnormalities have been studied extensively, there are few studies focusing on their prevalence in developing countries (3-5). We also investigated the association between del(13)(q14) and the proliferative and apoptotic indexes of bone marrow plasma cells (PC) in order to study the possible role of this abnormality in the biology of the disease.…”

Plasma Cell Neoplasms

“…However, G-banding remains fundamental to testing in plasma cell neoplasms, as it can detect abnormalities (e.g., ploidy status) that cannot be completely characterized by FISH alone or that are masked by FISH (e.g., near-tetraploidy may mask losses involving chromosome 13 and the IGH locus [109]). Additionally, the finding of karyotypically abnormal cells by G-banding has been used as a marker for the proliferative activity of the malignant plasma cells [35,110].…”