Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma

Dewald, Gordon W.; Therneau, Terry M.; Larson, Dirk R.; Lee, You Kyoung; Fink, Stephanie; Smoley, Stephanie A.; Paternoster, Sarah F.; Adeyinka, Adewale; Ketterling, Rhett P.; Dyke, Daniel L. Van; Fonseca, Rafaël; Kyle, Robert A.

doi:10.1182/blood-2005-05-1981

Cited by 112 publications

(84 citation statements)

References 21 publications

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“…16,17 The presence of D13 was associated with an adverse prognosis when studied by either metaphase analysis or iFISH, on both univariate (Po0.001 for both) and multivariate (P ¼ 0.002, cytogenetics; P ¼ 0.046, iFISH) analysis. However, although detected in considerably fewer patients (18% by cytogenetics vs 47% by iFISH), D13 detected in metaphases imparted a significantly shorter OS than D13 by iFISH (MS 15 vs 29 months).…”

Section: Discussionmentioning

confidence: 99%

“…This conclusion has been drawn from comparison of different publications as few studies, with variable results, have directly compared conventional cytogenetic and iFISH data from the same patients. [15][16][17] In this study, we have examined the effect of D13 on prognosis by both cytogenetics and iFISH in a large cohort of patients from different UK centers and compared the prognostic significance according to the detection method used.…”

Section: Introductionmentioning

confidence: 99%

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Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma

et al. 2006

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In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (D13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n ¼ 794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if D13, p53 deletion or t(4;14) was present, but only D13 remained significant on multivariate analysis. Patients with D13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with D13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable D13 disappeared; their outcome matched that of patients with no detectable D13 (P ¼ 0.115). Addition of ploidy status to iFISH-D13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH D13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with D13. We conclude that D13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of D13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma

et al. 2006

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“…The reported studies to-date produced conflicting results. Cyclin-D1 overexpression has been linked to the t(11;14) translocation and polysomy of chromosome 11 [11] but the presence of a t(11;14) seems to be a prognostically ''neutral'' genetic abnormality [12,13]. In our study, the patients were diagnosed with MM from Jan 1, 2000 until December 31, 2007 and we had no fluorescent In situ hybridization or caryotype data.…”

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confidence: 85%

“…The overexpression of cyclin-D1 correlated with durable responses and better prognosis to bortezomib therapy in small series of patients [14][15][16] Furthermore, in another small study with 45 patients who received conventional chemotherapy (MP) plus rituximab, the cyclin-D1 immunohistochemical expression correlated with better prognosis [14]. On the other hand, cyclin-D1 negativity did not convey any adverse effect on progression free survival (PFS) or OS in 94 patients (49 newly diagnose and 45 with relapsed/refractory disease) who received the T-VAD (thalidomide, vincristine, adriamycin, dexamethasone) regimen [13]. The discrepancy between the above results can be explained by the differences in the population, i.e., the immunoactivity of cyclin-D1 was evaluated in small series of refractory or relapsed MM patients and not in large population of newly diagnosed patients, as in our study.…”

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confidence: 97%

Increased expression of cyclin‐D1 on trephine bone marrow biopsies independently predicts for shorter overall survival in patients with multiple myeloma treated with novel agents

et al. 2012

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Multiple myeloma (MM) comprises 1% of all malignancies and 13% of hematological malignancies in the Caucasian population. Yearly incidence is 4/100,000 in the US and is higher in blacks and males [1]. The pathogenesis of the disease is relatively unknown; several chromosomal abnormalities have been related to the development of the disease, but none is characteristic of MM. Cyclin-D1 is a protein encoded by the CCND1 (bcl-1) gene on chromosome 11q13, and is an important regulator of G1 to S phase progression.Overexpression or overactivity of the CCND1 is common in malignancies including MM, mantle cell lymphoma, breast cancer, and hepatocellular cancer [2][3][4]. Previous studies have shown that CCND1 is expressed in 50% of patients with MM and that CCND1 overexpression represents an unfavorable prognostic factor in MM [5,6]. However, a recent study in a small number of patients showed that overexpressed CCND1 in MM is an independent prognostic marker associated with a more durable response to bortezomib. The aim of our study was to evaluate the impact of the immunohistochemical expression of cyclin-D1 in the plasma cells of trephine biopsies on survival of newly-diagnosed patients with MM who were treated with novel agents. One hundred and thirty consecutive patients with newly diagnosed MM were evaluated (66 males and 64 females). All patients were diagnosed, treated, and followed-up in a single center (Department of Clinical Therapeutics, University of Athens Medical School, Athens, Greece). Clinical characteristics of the patients are depicted in Table I. The median age of the patients was 68 years (range: 35-85 years). Forty-five patients (35%) had advanced disease at diagnosis (Stage 3 according to international staging system (ISS)). One hundred and fifteen patients (pts) had symptomatic disease that required therapy: 29 (25%) received bortezomib-based regimens (15 patients VTD (Bortezomib, Thalidomide and Dexamethasone), 5 patients VMP, and 5 patients PAD (Bortezomib, Doxorubicin and Dexamethasone)), 31 (26%) received thalidomide-based regimens (21 patients melphalan prednisone and thalidomide (MPT) and 10 patients thalidomide, vincristine, doxorubicin, dexamethasone (T-VAD)), and 55 received conventional treatment (20 patients VAD and 35 patients melphalan and prednisone) as first-line therapy, while all patients received regimens containing bortezomib or an immunomodulatory agents at some point during the course of their disease. Nineteen patients (16.5%) received high-dose melphalan plus autologous stem cell transplantation (ASCT). The median follow-up time for these patients was 22 months.Among patients with symptomatic myeloma (N 5 115), positive staining for cyclin-D1 (Fig. 1) was found in 35 (30%) patients, for CD56 in 45 (39%), for CD117 in 94 (81%), and for CD27 in 72 (62%) patients. In patients with asymptomatic/smoldering myeloma, positive staining for cyclin-D1 was found only in 1 (7%) patient, for CD56 in 9 (64%), and for CD117 in 6 (43%) (P < 0.01 for all comparisons compared to symptomatic...

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“…Patients with isolated deletion 13 (del13) on FISH analysis do not have a worse outcome, unless this abnormality is associated with (del17) or t (4;14). (8,9) (Table 1) Patients with symptomatic MM should be treated immediately; early intervention on asymptomatic patients showed no benefits, and observation alone is the standard. (10)(11)(12) Treatment choice should be based on both patient's characteristics, in particular age, and scientific evidence.…”

Section: Diagnosis and Treatment Strategymentioning

confidence: 99%

Management of older patients with multiple myeloma

Gay

Palumbo

2011

Blood Reviews

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For many years, the oral combination melphalan-prednisone (MP) has been considered the standard of care for patients with multiple myeloma (MM) not eligible for autologous stem cell transplantation. In the era of novel agents, the introduction of immunomodulatory drugs and proteasome inhibitors has challenged the role of MP and lead to new standards of care for this disease. Five randomized phase III studies compared the traditional MP with the MP plus thalidomide (MPT). All these studies showed a prolonged time to progression (TTP) with the 3-drug combination. However, in only two of these trials this advantage translated into an improvement in overall survival (OS). In another randomized trial, MP plus bortezomib (VMP) was correlated with an increase in both TTP and OS compared with MP. Preliminary data showed the

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Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma

Cited by 112 publications

References 21 publications

Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma

Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma

Increased expression of cyclin‐D1 on trephine bone marrow biopsies independently predicts for shorter overall survival in patients with multiple myeloma treated with novel agents

Management of older patients with multiple myeloma

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