Prognostic Implications of Monosomies in Patients With Multiple Myeloma

2017 ◽  
Vol 17 (3) ◽  
pp. 159-164.e2 ◽  
Author(s):  
Sang-Yong Shin ◽  
Hyeon-Seok Eom ◽  
Ji Yeon Sohn ◽  
Hyewon Lee ◽  
Boram Park ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Implications

scholarly journals Gain/Amplification of Chromosome Arm 1q21 in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 256
Author(s):  
Ichiro Hanamura
Keyword(s):  
Multiple Myeloma ◽  
Hematological Malignancy ◽  
Treatment Approach ◽  
Current Knowledge ◽  
Chromosome 1 ◽  
Plasma Cell Neoplasm ◽  
Chromosome Arm ◽  
Cell Neoplasm ◽  
Prognostic Implications ◽  
Tandem Duplications

Multiple myeloma (MM), a plasma cell neoplasm, is an incurable hematological malignancy characterized by complex genetic and prognostic heterogeneity. Gain or amplification of chromosome arm 1q21 (1q21+) is the most frequent adverse chromosomal aberration in MM, occurring in 40% of patients at diagnosis. It occurs in a subclone of the tumor as a secondary genomic event and is more amplified as the tumor progresses and a risk factor for the progression from smoldering multiple myeloma to MM. It can be divided into either 1q21 gain (3 copies) or 1q21 amplification (≥4 copies), and it has been suggested that the prognosis is worse in cases of amplification than gain. Trisomy of chromosome 1, jumping whole-arm translocations of chromosome1q, and tandem duplications lead to 1q21+ suggesting that its occurrence is not consistent at the genomic level. Many studies have reported that genes associated with the malignant phenotype of MM are situated on the 1q21 amplicon, including CKS1B, PSMD4, MCL1, ANP32E, and others. In this paper, we review the current knowledge regarding the clinical features, prognostic implications, and the speculated pathology of 1q21+ in MM, which can provide clues for an effective treatment approach to MM patients with 1q21+.

scholarly journals Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities

Blood ◽  
1995 ◽  
Vol 86 (11) ◽  
pp. 4250-4256 ◽  
Author(s):  
G Tricot ◽  
B Barlogie ◽  
S Jagannath ◽  
D Bracy ◽  
S Mattox ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Poor Prognosis ◽  
Chromosomal Abnormalities ◽  
Multivariate Regression Analysis ◽  
Significant Variable ◽  
Chromosome 13 ◽  
Reactive Protein ◽  
Dismal Prognosis ◽  
Prognostic Implications ◽  
Beta 2 Microglobulin

Chromosomal abnormalities have major biologic and prognostic implications in leukemias. Cytogenetic information in typically hypoproliferative multiple myeloma (MM) is limited because of difficulties in obtaining analyzable metaphases. In this study, karyotypes and other known prognostic factors were analyzed in 155 newly diagnosed MM patients, entered on an intensive treatment program with two autotransplants. Complete remission (CR), event-free (EFS) and overall survival (OS) were analyzed using standard statistical methods. Abnormal cytogenetics were found in 39% of patients and were associated with a significantly lower CR rate (27% v 48%; P = .008). EFS and OS were inferior in patients with either partial or complete deletion of chromosome 13 or 11q abnormalities (“unfavorable” karyotype) when compared with the remaining patients (P < .001) who, as a group, had a similar prognosis irrespective of cytogenetic findings, ie, inevaluable, normal, or abnormal but without an “unfavorable” karyotype. The patients with abnormalities of both chromosomes 11 and 13 had a dismal prognosis with median EFS and OS of only 11 and 12 months, respectively. Significant associations were noted between an “unfavorable” karyotype and IgA isotype, elevated levels of beta-2 microglobulin (B2M, > or = 3 mg/L) and age > 60 years. On multivariate regression analysis, the absence of an “unfavorable” karyotype was the most significant variable associated with prolonged EFS and OS (P = .0001 and .0002, respectively). Other independent favorable variables were age less than 60 years, C-reactive protein (CRP) < or = 0.4 mg/dL and bone marrow plasmacytosis < or = 50% before treatment. On a multivariate analysis without cytogenetics, these same three standard parameters were identified as the only favorable variables. Patients not having all three standard favorable variables had a significantly lower CR rate (P = .03), EFS (P = .0001), and OS (P = .002) if an unfavorable karyotype was detected. We conclude that, in this program of uniformly treated MM patients, a poor prognosis was associated predominantly with abnormalities of chromosomes 11 and 13.

Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3849-3856 ◽  
Author(s):  
John Shaughnessy ◽  
Joth Jacobson ◽  
Jeff Sawyer ◽  
Jason McCoy ◽  
Athanasios Fassas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Multiple Myeloma ◽  
Global Gene Expression ◽  
Cell Cycle Gene ◽  
Term Survival ◽  
Cytogenetic Abnormalities ◽  
Chromosome 13 ◽  
Prognostic Implications ◽  
Total Therapy

Abstract Metaphase cytogenetic abnormalities (CAs), especially of chromosome 13 (CA 13), confer a grave prognosis in multiple myeloma even with tandem autotransplantations as applied in Total Therapy I, which enrolled 231 patients between 1989 and 1994. With a median follow-up of almost 9 years, the prognostic implications of all individual CAs, detected prior to treatment and at relapse, were investigated. Among all CAs and standard prognostic factors examined prior to therapy, only hypodiploidy and CA 13 (hypo–13 CA), alone or in combination, were associated with shortest event-free survival and overall survival (OS). The shortest postrelapse OS was observed with hypo–13 CA, which was newly detected in 18 of all 28 patients presenting with this abnormality at relapse. Superior prognosis was associated with the absence of any CA at both diagnosis and relapse (10-year OS, 40%). The lack of independent prognostic implications of other CAs points to a uniquely aggressive behavior of hypo–13 CA (present in 16% of patients at diagnosis). With the use of microarray data in 146 patients enrolled in Total Therapy II, overexpression of cell cycle genes distinguished CA from no CA, especially in cases of del(13) detected by interphase fluorescence in situ hybridization (FISH). FISH 13, resulting in a haploinsufficiency of RB1 and other genes mapping to chromosome 13, as well as activation of IGF1R, appears to have an amplifying effect on cell cycle gene expression, thus providing a molecular explanation for the dire outcome of patients with CA 13 compared with those with other CAs.

Up-Front Thalidomide-Dexamethasone (THAL) and Double Autologous Transplantation (Double TX) for Multiple Myeloma: Comparison with Double TX without Added Thalidomide and Prognostic Implications of Chromosome 13 Deletion and Translocation t(4;14).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3081-3081 ◽  
Author(s):  
Michele Cavo ◽  
Nicoletta Testoni ◽  
Carolina Terragna ◽  
Elena Zamagni ◽  
Paola Tacchetti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
Lower Probability ◽  
Fish Analysis ◽  
Primary Therapy ◽  
Cytogenetic Abnormalities ◽  
Chromosome 13 ◽  
Prognostic Implications ◽  
Intent To Treat

Abstract Aim of the present sudy was to evaluate the benefit of novel agents combined with conventional therapies in multiple myeloma (MM), with particular emphasis on patients (pts) carrying adverse cytogenetic abnormalities. For this purpose, we analyzed a series of 142 pts who received thalidomide-dexamethasone (thal-dex) and double autologous transplantation (double Tx). By study design, thal-dex was administered from the outset until the second autologous Tx. On an intent-to-treat basis, stringently defined (immumofixation negative) complete remission (CR) rate following double Tx and thal-dex was 54%. This value was significantly higher (P=0.0009) compared to the 33% observed in a comparable series of 129 pts who received double Tx without thal-dex. In comparison with these latter patients, addition of thal-dex to double Tx significantly prolonged PFS (median: 31 vs 42 months; P=0.04) and did not adversely affect survival after post-transplant relapse (P=0.7). All 142 pts included in the study were investigated at baseline for the presence of chromosome 13 deletion [del(13)] by FISH analysis and of t(4;14) using a RT-PCR assay. An analysis on an intent-to-treat basis performed according to the presence or absence of these cytogenetic abnormalities revealed that the probability to respond (more than 90% reduction in M protein concentration) to primary therapy with thal-dex for 94 pts who carried both del(13) and t(4;14) was significantly lower compared to that of 69 pts with del(13) alone (12% vs 41%, respectively; P=0.012) and of 18 pts with t(4;14) alone (12% vs 50%, respectively; P=0.006). The lower probability of response to first-line thal-dex therapy conferred by the presence of both del(13) and t(4;14) was completely offset by subsequent application of double Tx and thal-dex. Indeed, on an intent-to-treat basis, the probability to attain a very good partial response or CR for pts with both del(13) and t(4;14) positivity was 68% compared to 80% for pts with both del(13) and t(4;14) negativity (P=0.1). With a median follow-up of 24 months, the 3-year projected probabilities of OS and PFS were 80% and 59%, respectively (intent-to-treat). The presence or absence of t(4;14) had no significant impact on the 3-year projected probability of OS (80.12% vs 80.42%, respectively; P=0.3). Furthermore, an analysis of pts who actually received thal-dex and double Tx showed that curves of OS and EFS were almost superimposable among pts who carried or lacked both del(13) and t(4;14). Indeed, the 3-year projected probability of OS for pts with both these cytogenetic abnormalities was 92% compared to 88% for pts who were negative for both del(13) and t(4;14); (P=0.7); the corresponding figures for EFS were 70% vs 77%, respectively (P=0.9). These results suggest that thal-dex combined with double Tx may overcome the unfavourable prognosis conferred by del(13) and t(4;14). A longer follow-up is required before definite conclusions can be drawn.

scholarly journals Prognostic implications of p21 (Waf1/Cip1) immunolocalization in multiple myeloma

2005 ◽  
Vol 26 (3) ◽  
pp. 91-98 ◽  
Author(s):  
Masahiko OHATA ◽  
Shinobu NAKAMURA ◽  
Hiroyuki FUJITA ◽  
Mamoru ISEMURA
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Implications ◽  
P21 Waf1

scholarly journals Prognostic implications of tumor cell DNA and RNA content in multiple myeloma

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 338-341 ◽  
Author(s):  
B Barlogie ◽  
R Alexanian ◽  
D Dixon ◽  
L Smith ◽  
L Smallwood ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Initial Response ◽  
Progressive Increase ◽  
Tumor Burden ◽  
Remission Induction ◽  
Chemotherapy Sensitivity ◽  
Dna And Rna ◽  
Flow Cytometric ◽  
Rna Content ◽  
Prognostic Implications

Flow cytometric studies of bone marrow DNA and RNA content were conducted in 71 previously untreated patients with multiple myeloma. There was a progressive increase in response rate with rising plasma cell RNA content. The DNA-derived ploidy level also affected chemotherapy sensitivity: only one of 11 patients with either hypodiploidy or biclonal DNA stemlines responded. DNA-RNA-defined marrow plasmacytosis was the only tumor mass-related variable adversely affecting remission induction. Survival was longer in patients with low tumor burden and favorable DNA features. The availability of objective and quantitative pretreatment variables associated with both initial response and survival should permit a risk-based selection of patients for novel treatment approaches.

scholarly journals Multiple Myeloma of the Thyroid Cartilage

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Peter Kalina ◽  
Jeffrey B. Rykken
Keyword(s):  
Multiple Myeloma ◽  
Maxillary Sinus ◽  
Plasma Cell ◽  
Thyroid Cartilage ◽  
Autologous Stem Cell Transplant ◽  
Neck Mass ◽  
Cell Transplant ◽  
Plasma Cell Neoplasm ◽  
Prognostic Implications ◽  
Left Maxillary Sinus

A 60-year-old male presented with hoarseness. His past medical history was remarkable for a plasmacytoma of the left maxillary sinus having been resected without systemic evidence of plasma cell myeloma (PCM), also known as multiple myeloma (MM), at the time. This maxillary sinus disease recurred and was treated with radiation. Workup for PCM was conducted. Treatment included melphalan and autologous stem cell transplant. Because of the therapeutic and prognostic implications, a Plasma cell neoplasm (PCN) in a neck mass must be carefully evaluated by clinical and pathological criteria in order to distinguish plasmacytoma from PCM. PCN involvement of the thyroid cartilage is very rare, with only 5 previously reported cases.

scholarly journals Immunoglobulin isotypes in multiple myeloma: laboratory correlates and prognostic implications in total therapy protocols

2009 ◽  
Vol 145 (1) ◽  
pp. 134-137 ◽  
Author(s):  
Bijay Nair ◽  
Sarah Waheed ◽  
Jackie Szymonifka ◽  
John D Shaughnessy Jr ◽  
John Crowley ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immunoglobulin Isotypes ◽  
Prognostic Implications ◽  
Total Therapy
Sign in / Sign up

Export Citation Format

Share Document