title: Double hit lymphoma: the MD Anderson Cancer Center clinical experience.
abstract: We report our experience with 129 cases of double hit lymphoma (DHL), defined as B-cell lymphoma with translocations and/or extra signals involving MYC plus BCL2 and/or BCL6. All cases were reviewed for histopathological classification. Median age was 62 years (range, 18-85), 84% of patients had advanced-stage disease, and 87% had an International Prognostic Index score ≥2. Fourteen patients (11%) had a history of low-grade follicular lymphoma. MYC translocation was present in 81%, and extra signals of MYC in 25% of patients. IGH-BCL2 translocation was present in 84% and extra signals of BCL2 in 12% of patients. Two-year event-free survival (EFS) rates in all patients and patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and R-HyperCVAD/MA (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate) were 33%, 25%, 67% and 32%, respectively. In patients achieving complete response with initial therapy (n = 71), 2-year EFS rates in patients who did (n = 23) or did not (n = 48) receive frontline stem cell transplantation were 68% and 53%, respectively (P = 0·155). The cumulative incidence of central nervous system involvement was 13% at 3 years. Multivariate analysis identified performance status ≥2 and bone marrow involvement as independent adverse prognostic factors for EFS and OS. Further research is needed to identify predictive and/or targetable biological markers and novel therapeutic approaches for DHL patients.
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.forename: Mansoor
authors.initials: M
authors.lastname: Noorani
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: Richard E
authors.initials: RE
authors.lastname: Davis
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
authors.forename: Long
authors.initials: L
authors.lastname: Ma
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ahmed
authors.forename: Maria Alma
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: Fredrick B
authors.initials: FB
authors.lastname: Hagemeister
authors.forename: Nathan
authors.initials: N
authors.lastname: Fowler
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Fanale
authors.forename: Loretta
authors.initials: L
authors.lastname: Nastoupil
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.forename: Hun J
authors.initials: HJ
authors.lastname: Lee
authors.forename: Bouthaina S
authors.initials: BS
authors.lastname: Dabaja
authors.forename: Chelsea C
authors.initials: CC
authors.lastname: Pinnix
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Yago
authors.initials: Y
authors.lastname: Nieto
authors.forename: Issa
authors.initials: I
authors.lastname: Khouri
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.forename: Francesco
authors.initials: F
authors.lastname: Turturro
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fayad
authors.forename: Jason R
authors.initials: JR
authors.lastname: Westin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D019254:Genes, bcl-2 / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D051560:Proto-Oncogene Proteins c-bcl-6; D012189:Retrospective Studies; D014178:Translocation, Genetic / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6
keywords: BCL2; BCL6; MYC; double hit lymphoma; prognostic factors