Deletion of chromosome 13q14 detected by fluorescence in situ hybridization has prognostic impact on survival after high-dose therapy in patients with multiple myeloma

2001 ◽  
Vol 80 (6) ◽  
pp. 345-348 ◽  
Author(s):  
Worel N. ◽  
Greinix H. ◽  
Ackermann J. ◽  
Kaufmann H. ◽  
Urbauer E. ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
High Dose ◽  
Prognostic Impact ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Impact On Survival ◽  
Chromosome 13Q14

Achievement of at Least Very Good Partial Response Is a Simple and Robust Prognostic Factor in Patients With Multiple Myeloma Treated With High-Dose Therapy: Long-Term Analysis of the IFM 99-02 and 99-04 Trials

2009 ◽  
Vol 27 (34) ◽  
pp. 5720-5726 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Herve Avet-Loiseau ◽  
Michel Attal ◽  
Catherine Charbonnel ◽  
Frederic Garban ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
High Dose ◽  
Prognostic Impact ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Good Partial Response

Purpose The prognostic impact of complete response (CR) achievement in multiple myeloma (MM) has been shown mostly in the context of autologous stem-cell transplantation. Other levels of response have been defined because, even with high-dose therapy, CR is a relatively rare event. The purpose of this study was to analyze the prognostic impact of very good partial response (VGPR) in patients treated with high-dose therapy. Patients and Methods All patients were included in the Intergroupe Francophone du Myelome 99-02 and 99-04 trials and treated with vincristine, doxorubicin, and dexamethasone (VAD) induction therapy followed by double autologous stem-cell transplantation (ASCT). Best post-ASCT response assessment was available for 802 patients. Results With a median follow-up of 67 months, median event-free survival (EFS) and 5-year EFS were 42 months and 34%, respectively, for 405 patients who achieved at least VGPR after ASCT versus 32 months and 26% in 288 patients who achieved only partial remission (P = .005). Five-year overall survival (OS) was significantly superior in patients achieving at least VGPR (74% v 61% P = .0017). In multivariate analysis, achievement of less than VGPR was an independent factor predicting shorter EFS and OS. Response to VAD had no impact on EFS and OS. The impact of VGPR achievement on EFS and OS was significant in patients with International Staging System stages 2 to 3 and for patients with poor-risk cytogenetics t(4;14) or del(17p). Conclusion In the context of ASCT, achievement of at least VGPR is a simple prognostic factor that has importance in intermediate and high-risk MM and can be informative in more patients than CR.

The Prognostic Impact of MYC Gene-Related Abnormalities on Multiple Myeloma Outcome through Fluorescence in situ Hybridization Analysis

2022 ◽  
Author(s):  
Yosuke Okada ◽  
Masahiro Teramoto ◽  
Noriaki Tachi ◽  
Toshikuni Kawamura ◽  
Toshikatsu Horiuchi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Chromosomal Abnormalities ◽  
Hybridization Analysis ◽  
Chromosome 8 ◽  
Prognostic Impact ◽  
Additional Chromosome ◽  
Myc Gene

Introduction: Chromosomal abnormalities (CAs) have been identified as important factors in determining the biological features and prognostic value of multiple myeloma (MM). MYC gene-related abnormalities (MYC GAs) are one of the CAs, but its unfavorable impact has not been fully investigated in daily clinical practice. Methods: This study retrospectively analyzed the prognostic impact of MYC GAs on 81 patients through fluorescence in situ hybridization analysis in our institute. Results: MYC GAs were associated with poor overall survival (hazard ratio [HR], 3.08; 95% confidence interval [CI], 1.23–7.73; p = 0.017), progression-free survival (PFS) (HR, 2.96; 95% CI, 1.58–5.53; p < 0.001), and time to next treatment (TNT) (HR, 2.11; 95% CI, 1.13–3.93; p = 0.018) in the median follow-up of 34.7 months. Furthermore, MYC GAs with an additional chromosome 8 (MYC-Ch8(+)) were associated with shorter PFS (HR, 3.15; 95% CI, 1.38–7.2; p = 0.0064), whereas MYC GAs without an additional chromosome 8 (MYC-Ch8(−)) were associated with shorter PFS (HR, 3.62; 95% CI, 1.51–8.68; p = 0.004) and shorter TNT (HR, 3.72; 95% CI, 1.41–9.81; p = 0.0078). Conclusion: These findings could help identify high-risk patients with MM. Further prospective studies are needed to confirm the significance of MYC GAs for the MM prognostic effect.

Frequent Gains of Chromosome Arm 1q21 in Plasma Cell Dyscrasia Detected by Fluorescence In Situ Hybridization: Incidence Increases from MGUS to Relapsed Myeloma and Is Related to Disease Progression and Prognosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1553-1553
Author(s):  
Ichiro Hanamura ◽  
Peter Stewart ◽  
Frederica Cavallo ◽  
Bart Burington ◽  
Erik Rasmussen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Disease Progression ◽  
Standard Of Care ◽  
Recurrent Event ◽  
Plasma Cell Dyscrasia ◽  
High Dose

Abstract Background: High-dose therapy with autologous stem cell transplantation (HDT-ASCT), effecting complete remissions in &gt; 40% with median overall survival exceeding 6 years, has become the standard of care for patients with multiple myeloma (MM). Poor outcome following HDT-ASCT has been linked most strongly to metaphase cytogenetic abnormalities (CA). Tandem duplications and jumping translocations of the chromosome 1q21 region is a recurrent event in advanced MM and 1q21 amplification (amp1q21) and high expression of the CKS1B gene (mapping to 1q21), both signify poor survival in MM treated with HDT-ASCT. Smoldering multiple myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) have many of the genetic hallmarks of overt MM, but especially MGUS rarely proceeds to MM requiring treatment. The aim of this study was determine if amp1q21 relates to disease progression and prognosis. Patients and Methods: 467 untreated patients with MGUS (n = 14), SMM (n = 32) and MM (n = 421) as well as 42 with relapsed MM were examined by means of triple color interphase fluorescence in situ hybridization (TRI-FISH) of the CKS1B locus. Results: The frequency of ampq21 was 0% in 14 patients with MGUS, 43% in 32 with SMM, 43% in 421 with newly diagnosed MM and 78% in 42 with relapsed MM (p&lt;0.001; untreated vs relapsed MM). Among SMM patients, 11 of 14 (78%) with amp1q21 but only 2 of 18 (11%) without amp1q21 progressed to active MM (p&lt;0.001) (median follow-up, 44 mo; range, 0–120 mo). In 421 MM patients treated on Total Therapy 2 (high-dose melphalan-based tandem autotransplants +/− thalidomide), 5-yr overall survival/event-free survival were 75%/61% in without amp1q21 compared to 48%/34% with amp1q21 (both p&lt;0.001). Among 42 relapses, amp1q21 was present in 20/21 occurring on thalidomide vs 13/21 on no thalidomide (p=0.020); the median post-relapse survival in those with amp1q21 was only 11 mo vs 25 mo in patients without amp1q21 (p=0.02). Conclusion: (1) Amp1q21 was absent in MGUS and present in &gt;40% of symptomatic MM and SMM. (2) in SMM, amp1q21 was associated with a higher risk of conversion to MM. (3) In overt MM, amp1q21 conferred inferior event-free and overall survival.

scholarly journals Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4696-4700 ◽  
Author(s):  
Nikhil C. Munshi ◽  
Kenneth C. Anderson ◽  
P. Leif Bergsagel ◽  
John Shaughnessy ◽  
Antonio Palumbo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
High Risk ◽  
Risk Stratification ◽  
Fluorescence In Situ Hybridization ◽  
High Serum ◽  
Β2 Microglobulin ◽  
Poor Outcome ◽  
13Q Deletion

Abstract A panel of members of the 2009 International Myeloma Workshop developed guidelines for risk stratification in multiple myeloma. The purpose of risk stratification is not to decide time of therapy but to prognosticate. There is general consensus that risk stratification is applicable to newly diagnosed patients; however, some genetic abnormalities characteristic of poor outcome at diagnosis may suggest poor outcome if only detected at the time of relapse. Thus, in good-risk patients, it is necessary to evaluate for high-risk features at relapse. Although detection of any cytogenetic abnormality is considered to suggest higher-risk disease, the specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4;14) and del17p, and detection by fluorescence in situ hybridization of t(4;14), t(14;16), and del17p. Detection of 13q deletion by fluorescence in situ hybridization only, in absence of other abnormalities, is not considered a high-risk feature. High serum β2-microglobulin level and International Staging System stages II and III, incorporating high β2-microglobulin and low albumin, are considered to predict higher risk disease. There was a consensus that the high-risk features will change in the future, with introduction of other new agents or possibly new combinations.

scholarly journals Prognostic value of bone marrow angiogenesis in patients with multiple myeloma undergoing high-dose therapy

2004 ◽  
Vol 34 (3) ◽  
pp. 235-239 ◽  
Author(s):  
S Kumar ◽  
M A Gertz ◽  
A Dispenzieri ◽  
M Q Lacy ◽  
L A Wellik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Value ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy

Total Therapy With Tandem Transplants for Newly Diagnosed Multiple Myeloma

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 55-65 ◽  
Author(s):  
B. Barlogie ◽  
S. Jagannath ◽  
K.R. Desikan ◽  
S. Mattox ◽  
D. Vesole ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Remission Induction ◽  
Comprehensive Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Total Therapy ◽  
Macrophage Colony ◽  
Intent To Treat

Abstract Between August 1990 and August 1995, 231 patients (median age 51, 53% Durie-Salmon stage III, median serum β-2-microglobulin 3.1 g/L, median C-reactive protein 4 g/L) with symptomatic multiple myeloma were enrolled in a program that used a series of induction regimens and two cycles of high-dose therapy (“Total Therapy”). Remission induction utilized non–cross-resistant regimens (vincristine-doxorubicin-dexamethasone [VAD], high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor with peripheral blood stem cell collection, and etoposide-dexamethasone-cytarabine-cisplatin). The first high-dose treatment comprised melphalan 200 mg/m2 and was repeated if complete (CR) or partial (PR) remission was maintained after the first transplant; in case of less than PR, total body irradiation or cyclophosphamide was added. Interferon--2b maintenance was used after the second autotransplant. Fourteen patients with HLA-compatible donors underwent an allograft as their second high-dose therapy cycle. Eighty-eight percent completed induction therapy whereas first and second transplants were performed in 84% and 71% (the majority within 8 and 15 months, respectively). Eight patients (3%) died of toxicity during induction, and 2 (1%) and 6 (4%) during the two transplants. True CR and at least a PR (PR plus CR) were obtained in 5% (34%) after VAD, 15% (65%) at the end of induction, and 26% (75%) after the first and 41% (83%) after the second transplants (intent-to-treat). Median overall (OS) and event-free (EFS) survival durations were 68 and 43 months, respectively. Actuarial 5-year OS and EFS rates were 58% and 42%, respectively. The median time to disease progression or relapse was 52 months. Among the 94 patients achieving CR, the median CR duration was 50 months. On multivariate analysis, superior EFS and OS were observed in the absence of unfavorable karyotypes (11q breakpoint abnormalities, -13 or 13-q) and with low β-2-microglobulin at diagnosis. CR duration was significantly longer with early onset of CR and favorable karyotypes. Time-dependent covariate analysis suggested that timely application of a second transplant extended both EFS and OS significantly, independent of cytogenetics and β-2-microglobulin. Total Therapy represents a comprehensive treatment approach for newly diagnosed myeloma patients, using multi-regimen induction and tandem transplantation followed by interferon maintenance. As a result, the proportion of patients attaining CR increased progressively with continuing therapy. This observation is particularly important because CR is a sine qua non for long-term disease control and, eventually, cure.

Delphi-Panel Analysis of Appropriateness of High-Dose Therapy and Bone Marrow Autotransplants in Newly Diagnosed Multiple Myeloma

1999 ◽  
Vol 33 (5-6) ◽  
pp. 511-519 ◽  
Author(s):  
Robert Peter Gale ◽  
Rolla Edward Park ◽  
Robert W. Dubois ◽  
Kenneth C. Anderson ◽  
William M. Audeh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Delphi Panel ◽  
High Dose ◽  
Panel Analysis ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Dose Therapy
Sign in / Sign up

Export Citation Format

Share Document