Complex karyotype and translocation t(4;14) define patients
with high-risk newly diagnosed multiple myeloma: results of
CMG2002 trial

J 2012

Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial

NĚMEC, Pavel; Zuzana ZEMANOVA; Petr KUGLÍK; Kyra MICHALOVÁ; Jana TAJTLOVA et al.

Základní údaje

Originální název

Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial

Autoři

Vydání

Leukemia & Lymphoma, LONDON, INFORMA HEALTHCARE, 2012, 1042-8194

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30000 3. Medical and Health Sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 2.301

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/12:00061479

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.3109/10428194.2011.634042

UT WoS

000303070900028

Klíčová slova anglicky

Multiple myeloma; chromosomal abnormalities; prognostic factors; stem cell transplantation; cytogenetics and molecular genetics

Příznaky

Mezinárodní význam

Změněno: 23. 4. 2013 08:12, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

The prognostic impact of chromosomal abnormalities was evaluated by fluorescence in situ hybridization with cytoplasmic immunoglobulin light chain staining (cIg-FISH) and by classical metaphase cytogenetics in a cohort of 207 patients with newly diagnosed multiple myeloma who were treated with high-dose therapy followed by autologous stem cell transplantation in the CMG2002 clinical trial. The incidence of chromosomal abnormalities detected by FISH was as follows: 52.7% for del(13)(q14), 6.5% for del(17)(p13), 18.6% for t(11;14)(q13;q32), 22.8% for t(4;14)(p16;q32) and 45.7% for gain(1)(q21). Metaphase cytogenetic analysis revealed a complex karyotype in 19.1% and hyperdiploidy in 21.7% of patients. The overall response rate was not influenced by the presence of any studied chromosomal abnormality. Patients with a complex karyotype, those with translocation t(4;14) and those with gain of the 1q21 locus had a shorter time to progression (TTP) and overall survival (OS). Other genomic changes such as translocation t(11; 14) and del(13q) had less impact on TTP and OS. In multivariate analysis, complex karyotype, translocation t(4;14) and beta(2)-microglobulin level > 2.5 mg/L were independent prognostic factors associated with poor overall survival. Their unfavorable prognostic impact was even more pronounced if they were present in combination. Patients with t(4;14) present together with a complex karyotype had the worst prognosis, with a median OS of only 13.2 months, whereas patients with a normal karyotype or karyotype with <= 2 chromosomal changes had the best outcome, with 3-year OS of 85.9%. In conclusion, complex karyotype, gain of 1q21 region and translocation t(4;14) are major prognostic factors associated with reduced survival of patients with newly diagnosed multiple myeloma treated with autologous stem cell transplantation.

Návaznosti

LC06027, projekt VaV

Název: Univerzitní výzkumné centrum - Česká myelomová skupina (Akronym: LC MGUS)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Univerzitní výzkumné centrum - Česká myelomová skupina (URC - CMG)

MSM0021622415, záměr

Název: Molekulární podstata buněčných a tkáňových regulací

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Molekulární podstata buněčných a tkáňových regulací

MSM0021622434, záměr

Název: Od klasických prognostických markerů ke klinicky aplikovatelným farmakogenomickým a farmakoproteomickým projektům u mnohočetného myelomu a monoklonálních gamapatií

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Od klasických prognostických markerů ke klinicky aplikovatelným farmakogenomickým a farmakoproteomickým projektům u mnohočetného myelomu a monoklonálních gamapatií

MUNI/A/1012/2009, interní kód MU

Název: Optimalizace diagnostiky a terapie maligních chorob a komplikací, které tyto maligní nemoci provázejí, s využitím nových molekulárně biologických metod.

Investor: Masarykova univerzita, Optimalizace diagnostiky a terapie maligních chorob a komplikací, které tyto maligní nemoci provázejí, s využitím nových molekulárně biologických metod., DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

NS10207, projekt VaV

Název: Úloha abnormalit chromozómu 1 a kaskády NF-kappaB v patogenezi mnohočetného myelomu

Investor: Ministerstvo zdravotnictví ČR, Úloha abnormalit chromozómu 1 a kaskády NF-kappaβ v patogenezi mnohočetného myelomu

Citovat

NĚMEC, Pavel; Zuzana ZEMANOVA; Petr KUGLÍK; Kyra MICHALOVÁ; Jana TAJTLOVA; Petra KAISAROVÁ; Alexandra OLTOVA; Hana FILKOVÁ; Milena HOLZEROVÁ; Jana BALCÁRKOVÁ; Marie JAROSOVA; Jana BARABÁŠOVÁ; Martina HRUBANOVÁ; Ivan SPICKA; Evzen GREGORA; Zdeněk ADAM; Vlastimil ŠČUDLA; Vladimír MAISNAR; Miroslava SCHUTZOVA a Roman HÁJEK. Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial. Leukemia & Lymphoma. LONDON: INFORMA HEALTHCARE, 2012, roč. 53, č. 5, s. 920-927. ISSN 1042-8194. Dostupné z: https://doi.org/10.3109/10428194.2011.634042.

@article{1070351,
   author = {Němec, Pavel and Zemanova, Zuzana and Kuglík, Petr and Michalová, Kyra and Tajtlova, Jana and Kaisarová, Petra and Oltova, Alexandra and Filková, Hana and Holzerová, Milena and Balcárková, Jana and Jarosova, Marie and Barabášová, Jana and Hrubanová, Martina and Spicka, Ivan and Gregora, Evzen and Adam, Zdeněk and Ščudla, Vlastimil and Maisnar, Vladimír and Schutzova, Miroslava and Hájek, Roman},
   article_location = {LONDON},
   article_number = {5},
   doi = {https://doi.org/10.3109/10428194.2011.634042},
   keywords = {Multiple myeloma; chromosomal abnormalities; prognostic factors; stem cell transplantation; cytogenetics and molecular genetics},
   language = {eng},
   issn = {1042-8194},
   journal = {Leukemia & Lymphoma},
   title = {Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial},
   volume = {53},
   year = {2012}
}

TY  - JOUR
ID  - 1070351
AU  - Němec, Pavel - Zemanova, Zuzana - Kuglík, Petr - Michalová, Kyra - Tajtlova, Jana - Kaisarová, Petra - Oltova, Alexandra - Filková, Hana - Holzerová, Milena - Balcárková, Jana - Jarosova, Marie - Barabášová, Jana - Hrubanová, Martina - Spicka, Ivan - Gregora, Evzen - Adam, Zdeněk - Ščudla, Vlastimil - Maisnar, Vladimír - Schutzova, Miroslava - Hájek, Roman
PY  - 2012
TI  - Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial
JF  - Leukemia & Lymphoma
VL  - 53
IS  - 5
SP  - 920-927
EP  - 920-927
PB  - INFORMA HEALTHCARE
SN  - 10428194
KW  - Multiple myeloma
KW  - chromosomal abnormalities
KW  - prognostic factors
KW  - stem cell transplantation
KW  - cytogenetics and molecular genetics
N2  - The prognostic impact of chromosomal abnormalities was evaluated by fluorescence in situ hybridization with cytoplasmic immunoglobulin light chain staining (cIg-FISH) and by classical metaphase cytogenetics in a cohort of 207 patients with newly diagnosed multiple myeloma who were treated with high-dose therapy followed by autologous stem cell transplantation in the CMG2002 clinical trial. The incidence of chromosomal abnormalities detected by FISH was as follows: 52.7% for del(13)(q14), 6.5% for del(17)(p13), 18.6% for t(11;14)(q13;q32), 22.8% for t(4;14)(p16;q32) and 45.7% for gain(1)(q21). Metaphase cytogenetic analysis revealed a complex karyotype in 19.1% and hyperdiploidy in 21.7% of patients. The overall response rate was not influenced by the presence of any studied chromosomal abnormality. Patients with a complex karyotype, those with translocation t(4;14) and those with gain of the 1q21 locus had a shorter time to progression (TTP) and overall survival (OS). Other genomic changes such as translocation t(11; 14) and del(13q) had less impact on TTP and OS. In multivariate analysis, complex karyotype, translocation t(4;14) and beta(2)-microglobulin level > 2.5 mg/L were independent prognostic factors associated with poor overall survival. Their unfavorable prognostic impact was even more pronounced if they were present in combination. Patients with t(4;14) present together with a complex karyotype had the worst prognosis, with a median OS of only 13.2 months, whereas patients with a normal karyotype or karyotype with <= 2 chromosomal changes had the best outcome, with 3-year OS of 85.9%. In conclusion, complex karyotype, gain of 1q21 region and translocation t(4;14) are major prognostic factors associated with reduced survival of patients with newly diagnosed multiple myeloma treated with autologous stem cell transplantation.
ER  -

NĚMEC, Pavel; Zuzana ZEMANOVA; Petr KUGLÍK; Kyra MICHALOVÁ; Jana TAJTLOVA; Petra KAISAROVÁ; Alexandra OLTOVA; Hana FILKOVÁ; Milena HOLZEROVÁ; Jana BALCÁRKOVÁ; Marie JAROSOVA; Jana BARABÁŠOVÁ; Martina HRUBANOVÁ; Ivan SPICKA; Evzen GREGORA; Zdeněk ADAM; Vlastimil ŠČUDLA; Vladimír MAISNAR; Miroslava SCHUTZOVA a Roman HÁJEK. Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial. \textit{Leukemia \&{} Lymphoma}. LONDON: INFORMA HEALTHCARE, 2012, roč.~53, č.~5, s.~920-927. ISSN~1042-8194. Dostupné z: https://doi.org/10.3109/10428194.2011.634042.

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