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.
abstract: 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.
authors.affiliation: Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Landsburg
authors.affiliation: Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
authors.forename: Marissa K
authors.initials: MK
authors.lastname: Falkiewicz
authors.affiliation: Division of Hematology/Oncology, Northwestern University, Chicago, IL, USA.|AbbVie, Chicago, IL, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Petrich
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Chu
authors.affiliation: Department of Pathology, Northwestern University, Chicago, IL, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Behdad
authors.affiliation: Department of Hematopathology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Hematopathology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Cassaday
authors.affiliation: Division of Hematology/Oncology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Nishitha M
authors.initials: NM
authors.lastname: Reddy
authors.affiliation: Lymphoma Study Group, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Bast
authors.affiliation: Division of Oncology & Hematology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.affiliation: Division of Hematology/Oncology, Loyola University Chicago, Chicago, IL, USA.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Kruczek
authors.affiliation: Division of Hematology/Oncology, Loyola University Chicago, Chicago, IL, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Smith
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Priyank
authors.initials: P
authors.lastname: Patel
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernandez-Ilizaliturri
authors.affiliation: Rush University Cancer Center, Rush University, Chicago, IL, USA.
authors.forename: Reem
authors.initials: R
authors.lastname: Karmali
authors.affiliation: Division of Hematology/Oncology, University of Wisconsin, Madison, WI, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Rajguru
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Yang
authors.affiliation: Division of Hematology/Oncology, Ohio State University, Columbus, OH, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Maly
authors.affiliation: Division of Hematology, Ohio State University, Columbus, OH, USA.
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Blum
authors.affiliation: Department of Pathology, Ohio State University, Columbus, OH, USA.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Vanslambrouck
authors.affiliation: Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005784:Gene Amplification; D015321:Gene Rearrangement; D016259:Genes, myc; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011379:Prognosis; D016016:Proportional Hazards Models; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: 
  
  MYC
  
  ; B cell lymphoma unclassifiable; chemotherapy; diffuse large B cell lymphoma; fluorescence in situ hybridization