Sole rearrangement but not amplification of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma and B cell lymphoma unclassifiable
Summary Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearran...
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| Veröffentlicht in: | British journal of haematology 2016-11, Vol.175 (4), p.631-640 |
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| creator | Landsburg, Daniel J. Falkiewicz, Marissa K. Petrich, Adam M. Chu, Benjamin A. Behdad, Amir Li, Shaoying Medeiros, L. Jeffrey Cassaday, Ryan D. Reddy, Nishitha M. Bast, Martin A. Vose, Julie M. Kruczek, Kimberly R. Smith, Scott E. Patel, Priyank Hernandez‐Ilizaliturri, Francisco Karmali, Reem Rajguru, Saurabh Yang, David T. Maly, Joseph J. Blum, Kristie A. Zhao, Weiqiang Vanslambrouck, Charles Nabhan, Chadi |
| description | Summary
Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC‐amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2‐year progression‐free survival rate (PFS) was 49% and 48% and 2‐year overall survival rate (OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2‐year PFS (59% vs. 23%, P = 0·006) but similar 2‐year OS as compared with SHL patients receiving R‐CHOP. SHL DLBCL patients treated with R‐CHOP, but not intensive induction, experienced significantly lower 2‐year PFS and OS (P |
| doi_str_mv | 10.1111/bjh.14282 |
| format | Article |
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Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC‐amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2‐year progression‐free survival rate (PFS) was 49% and 48% and 2‐year overall survival rate (OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2‐year PFS (59% vs. 23%, P = 0·006) but similar 2‐year OS as compared with SHL patients receiving R‐CHOP. SHL DLBCL patients treated with R‐CHOP, but not intensive induction, experienced significantly lower 2‐year PFS and OS (P < 0·001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/bjh.14282</identifier><identifier>PMID: 27469075</identifier><language>eng</language><publisher>England</publisher><subject>Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived - adverse effects ; Antibodies, Monoclonal, Murine-Derived - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; B cell lymphoma unclassifiable ; Biomarkers ; Bone Marrow - pathology ; chemotherapy ; Cyclophosphamide - adverse effects ; Cyclophosphamide - therapeutic use ; diffuse large B cell lymphoma ; Doxorubicin - adverse effects ; Doxorubicin - therapeutic use ; Female ; fluorescence in situ hybridization ; Gene Amplification ; Gene Rearrangement ; Genes, myc ; Humans ; Lymphoma, B-Cell - diagnosis ; Lymphoma, B-Cell - drug therapy ; Lymphoma, B-Cell - genetics ; Lymphoma, B-Cell - mortality ; Lymphoma, Large B-Cell, Diffuse - diagnosis ; Lymphoma, Large B-Cell, Diffuse - drug therapy ; Lymphoma, Large B-Cell, Diffuse - genetics ; Lymphoma, Large B-Cell, Diffuse - mortality ; Male ; Middle Aged ; MYC ; Neoplasm Staging ; Prednisone - adverse effects ; Prednisone - therapeutic use ; Prognosis ; Proportional Hazards Models ; Treatment Outcome ; Vincristine - adverse effects ; Vincristine - therapeutic use</subject><ispartof>British journal of haematology, 2016-11, Vol.175 (4), p.631-640</ispartof><rights>2016 John Wiley & Sons Ltd</rights><rights>2016 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4482-5b0acb92b14022a2e47b9270e4e452fdcf175933ca23201b1fb4cd0efc99027a3</citedby><cites>FETCH-LOGICAL-c4482-5b0acb92b14022a2e47b9270e4e452fdcf175933ca23201b1fb4cd0efc99027a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbjh.14282$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbjh.14282$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27469075$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Landsburg, Daniel J.</creatorcontrib><creatorcontrib>Falkiewicz, Marissa K.</creatorcontrib><creatorcontrib>Petrich, Adam M.</creatorcontrib><creatorcontrib>Chu, Benjamin A.</creatorcontrib><creatorcontrib>Behdad, Amir</creatorcontrib><creatorcontrib>Li, Shaoying</creatorcontrib><creatorcontrib>Medeiros, L. Jeffrey</creatorcontrib><creatorcontrib>Cassaday, Ryan D.</creatorcontrib><creatorcontrib>Reddy, Nishitha M.</creatorcontrib><creatorcontrib>Bast, Martin A.</creatorcontrib><creatorcontrib>Vose, Julie M.</creatorcontrib><creatorcontrib>Kruczek, Kimberly R.</creatorcontrib><creatorcontrib>Smith, Scott E.</creatorcontrib><creatorcontrib>Patel, Priyank</creatorcontrib><creatorcontrib>Hernandez‐Ilizaliturri, Francisco</creatorcontrib><creatorcontrib>Karmali, Reem</creatorcontrib><creatorcontrib>Rajguru, Saurabh</creatorcontrib><creatorcontrib>Yang, David T.</creatorcontrib><creatorcontrib>Maly, Joseph J.</creatorcontrib><creatorcontrib>Blum, Kristie A.</creatorcontrib><creatorcontrib>Zhao, Weiqiang</creatorcontrib><creatorcontrib>Vanslambrouck, Charles</creatorcontrib><creatorcontrib>Nabhan, Chadi</creatorcontrib><title>Sole rearrangement but not amplification of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma and B cell lymphoma unclassifiable</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC‐amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2‐year progression‐free survival rate (PFS) was 49% and 48% and 2‐year overall survival rate (OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2‐year PFS (59% vs. 23%, P = 0·006) but similar 2‐year OS as compared with SHL patients receiving R‐CHOP. SHL DLBCL patients treated with R‐CHOP, but not intensive induction, experienced significantly lower 2‐year PFS and OS (P < 0·001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction.</description><subject>Adult</subject><subject>Aged</subject><subject>Antibodies, Monoclonal, Murine-Derived - adverse effects</subject><subject>Antibodies, Monoclonal, Murine-Derived - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>B cell lymphoma unclassifiable</subject><subject>Biomarkers</subject><subject>Bone Marrow - pathology</subject><subject>chemotherapy</subject><subject>Cyclophosphamide - adverse effects</subject><subject>Cyclophosphamide - therapeutic use</subject><subject>diffuse large B cell lymphoma</subject><subject>Doxorubicin - adverse effects</subject><subject>Doxorubicin - therapeutic use</subject><subject>Female</subject><subject>fluorescence in situ hybridization</subject><subject>Gene Amplification</subject><subject>Gene Rearrangement</subject><subject>Genes, myc</subject><subject>Humans</subject><subject>Lymphoma, B-Cell - diagnosis</subject><subject>Lymphoma, B-Cell - drug therapy</subject><subject>Lymphoma, B-Cell - genetics</subject><subject>Lymphoma, B-Cell - mortality</subject><subject>Lymphoma, Large B-Cell, Diffuse - diagnosis</subject><subject>Lymphoma, Large B-Cell, Diffuse - drug therapy</subject><subject>Lymphoma, Large B-Cell, Diffuse - genetics</subject><subject>Lymphoma, Large B-Cell, Diffuse - mortality</subject><subject>Male</subject><subject>Middle Aged</subject><subject>MYC</subject><subject>Neoplasm Staging</subject><subject>Prednisone - adverse effects</subject><subject>Prednisone - therapeutic use</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Treatment Outcome</subject><subject>Vincristine - adverse effects</subject><subject>Vincristine - therapeutic use</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkkFvFCEYhonR2G314B8wHO1hWmCYZeZiYjdqNTUe1IMn8sHALg0DI8zY7A_yf5Z1aqMxJnIhwMPz8YYPoWeUnNEyztX17oxy1rIHaEXrdVMxyulDtCKEiIoS3h6h45yvCaE1aehjdMQEX3dENCv041P0BicDKUHYmsGECat5wiFOGIbRO-s0TC4GHC3-8HWDXcaQc9QOJtPjGzftMOAxxoTHFLch5gK4gMdyqbjyQvTO2jkb7CFtDb7A2niP_X4Yd3EADKH_a28O2pc6pTwob56gRxZ8Nk_v5hP05c3rz5vL6urj23ebV1eV5rxlVaMIaNUxRTlhDJjhoqwEMdzwhtleWyqarq41sJoRqqhVXPfEWN11hAmoT9DLxTvOajC9LgkSeDkmN0DaywhO_nkS3E5u43fZUNpS0hbBiztBit9mkyc5uHxIBsHEOUvaNkQIRlj9Hyhbi5p364P1dEF1ijknY-9fRIk8dIAsHSB_dkBhn_8e4Z789eUFOF-AG-fN_t8mefH-clHeAosQvhQ</recordid><startdate>201611</startdate><enddate>201611</enddate><creator>Landsburg, Daniel J.</creator><creator>Falkiewicz, Marissa K.</creator><creator>Petrich, Adam M.</creator><creator>Chu, Benjamin A.</creator><creator>Behdad, Amir</creator><creator>Li, Shaoying</creator><creator>Medeiros, L. Jeffrey</creator><creator>Cassaday, Ryan D.</creator><creator>Reddy, Nishitha M.</creator><creator>Bast, Martin A.</creator><creator>Vose, Julie M.</creator><creator>Kruczek, Kimberly R.</creator><creator>Smith, Scott E.</creator><creator>Patel, Priyank</creator><creator>Hernandez‐Ilizaliturri, Francisco</creator><creator>Karmali, Reem</creator><creator>Rajguru, Saurabh</creator><creator>Yang, David T.</creator><creator>Maly, Joseph J.</creator><creator>Blum, Kristie A.</creator><creator>Zhao, Weiqiang</creator><creator>Vanslambrouck, Charles</creator><creator>Nabhan, Chadi</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>201611</creationdate><title>Sole rearrangement but not amplification of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma and B cell lymphoma unclassifiable</title><author>Landsburg, Daniel J. ; Falkiewicz, Marissa K. ; Petrich, Adam M. ; Chu, Benjamin A. ; Behdad, Amir ; Li, Shaoying ; Medeiros, L. Jeffrey ; Cassaday, Ryan D. ; Reddy, Nishitha M. ; Bast, Martin A. ; Vose, Julie M. ; Kruczek, Kimberly R. ; Smith, Scott E. ; Patel, Priyank ; Hernandez‐Ilizaliturri, Francisco ; Karmali, Reem ; Rajguru, Saurabh ; Yang, David T. ; Maly, Joseph J. ; Blum, Kristie A. ; Zhao, Weiqiang ; Vanslambrouck, Charles ; Nabhan, Chadi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4482-5b0acb92b14022a2e47b9270e4e452fdcf175933ca23201b1fb4cd0efc99027a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antibodies, Monoclonal, Murine-Derived - adverse effects</topic><topic>Antibodies, Monoclonal, Murine-Derived - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>B cell lymphoma unclassifiable</topic><topic>Biomarkers</topic><topic>Bone Marrow - pathology</topic><topic>chemotherapy</topic><topic>Cyclophosphamide - adverse effects</topic><topic>Cyclophosphamide - therapeutic use</topic><topic>diffuse large B cell lymphoma</topic><topic>Doxorubicin - adverse effects</topic><topic>Doxorubicin - therapeutic use</topic><topic>Female</topic><topic>fluorescence in situ hybridization</topic><topic>Gene Amplification</topic><topic>Gene Rearrangement</topic><topic>Genes, myc</topic><topic>Humans</topic><topic>Lymphoma, B-Cell - diagnosis</topic><topic>Lymphoma, B-Cell - drug therapy</topic><topic>Lymphoma, B-Cell - genetics</topic><topic>Lymphoma, B-Cell - mortality</topic><topic>Lymphoma, Large B-Cell, Diffuse - diagnosis</topic><topic>Lymphoma, Large B-Cell, Diffuse - drug therapy</topic><topic>Lymphoma, Large B-Cell, Diffuse - genetics</topic><topic>Lymphoma, Large B-Cell, Diffuse - mortality</topic><topic>Male</topic><topic>Middle Aged</topic><topic>MYC</topic><topic>Neoplasm Staging</topic><topic>Prednisone - adverse effects</topic><topic>Prednisone - therapeutic use</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Treatment Outcome</topic><topic>Vincristine - adverse effects</topic><topic>Vincristine - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Landsburg, Daniel J.</creatorcontrib><creatorcontrib>Falkiewicz, Marissa K.</creatorcontrib><creatorcontrib>Petrich, Adam M.</creatorcontrib><creatorcontrib>Chu, Benjamin A.</creatorcontrib><creatorcontrib>Behdad, Amir</creatorcontrib><creatorcontrib>Li, Shaoying</creatorcontrib><creatorcontrib>Medeiros, L. Jeffrey</creatorcontrib><creatorcontrib>Cassaday, Ryan D.</creatorcontrib><creatorcontrib>Reddy, Nishitha M.</creatorcontrib><creatorcontrib>Bast, Martin A.</creatorcontrib><creatorcontrib>Vose, Julie M.</creatorcontrib><creatorcontrib>Kruczek, Kimberly R.</creatorcontrib><creatorcontrib>Smith, Scott E.</creatorcontrib><creatorcontrib>Patel, Priyank</creatorcontrib><creatorcontrib>Hernandez‐Ilizaliturri, Francisco</creatorcontrib><creatorcontrib>Karmali, Reem</creatorcontrib><creatorcontrib>Rajguru, Saurabh</creatorcontrib><creatorcontrib>Yang, David T.</creatorcontrib><creatorcontrib>Maly, Joseph J.</creatorcontrib><creatorcontrib>Blum, Kristie A.</creatorcontrib><creatorcontrib>Zhao, Weiqiang</creatorcontrib><creatorcontrib>Vanslambrouck, Charles</creatorcontrib><creatorcontrib>Nabhan, Chadi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Landsburg, Daniel J.</au><au>Falkiewicz, Marissa K.</au><au>Petrich, Adam M.</au><au>Chu, Benjamin A.</au><au>Behdad, Amir</au><au>Li, Shaoying</au><au>Medeiros, L. Jeffrey</au><au>Cassaday, Ryan D.</au><au>Reddy, Nishitha M.</au><au>Bast, Martin A.</au><au>Vose, Julie M.</au><au>Kruczek, Kimberly R.</au><au>Smith, Scott E.</au><au>Patel, Priyank</au><au>Hernandez‐Ilizaliturri, Francisco</au><au>Karmali, Reem</au><au>Rajguru, Saurabh</au><au>Yang, David T.</au><au>Maly, Joseph J.</au><au>Blum, Kristie A.</au><au>Zhao, Weiqiang</au><au>Vanslambrouck, Charles</au><au>Nabhan, Chadi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sole rearrangement but not amplification of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma and B cell lymphoma unclassifiable</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2016-11</date><risdate>2016</risdate><volume>175</volume><issue>4</issue><spage>631</spage><epage>640</epage><pages>631-640</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><abstract>Summary
Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC‐amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2‐year progression‐free survival rate (PFS) was 49% and 48% and 2‐year overall survival rate (OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2‐year PFS (59% vs. 23%, P = 0·006) but similar 2‐year OS as compared with SHL patients receiving R‐CHOP. SHL DLBCL patients treated with R‐CHOP, but not intensive induction, experienced significantly lower 2‐year PFS and OS (P < 0·001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction.</abstract><cop>England</cop><pmid>27469075</pmid><doi>10.1111/bjh.14282</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Antibodies, Monoclonal, Murine-Derived - adverse effects Antibodies, Monoclonal, Murine-Derived - therapeutic use Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use B cell lymphoma unclassifiable Biomarkers Bone Marrow - pathology chemotherapy Cyclophosphamide - adverse effects Cyclophosphamide - therapeutic use diffuse large B cell lymphoma Doxorubicin - adverse effects Doxorubicin - therapeutic use Female fluorescence in situ hybridization Gene Amplification Gene Rearrangement Genes, myc Humans Lymphoma, B-Cell - diagnosis Lymphoma, B-Cell - drug therapy Lymphoma, B-Cell - genetics Lymphoma, B-Cell - mortality Lymphoma, Large B-Cell, Diffuse - diagnosis Lymphoma, Large B-Cell, Diffuse - drug therapy Lymphoma, Large B-Cell, Diffuse - genetics Lymphoma, Large B-Cell, Diffuse - mortality Male Middle Aged MYC Neoplasm Staging Prednisone - adverse effects Prednisone - therapeutic use Prognosis Proportional Hazards Models Treatment Outcome Vincristine - adverse effects Vincristine - therapeutic use |
| title | Sole rearrangement but not amplification of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma and B cell lymphoma unclassifiable |
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