title: MYC+ diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation.
abstract: Approximately 5-10% of diffuse large B-cell lymphomas (DLBCL) harbor a 8q24/MYC rearrangement (MYC(+)). We determined the prognostic significance of MYC rearrangement in patients with relapsed/refractory DLBCL prospectively treated by R-ICE or R-DHAP followed by high-dose therapy and autologous stem cell transplantation. Twenty-eight (17%) of the 161 patients analyzed presented a MYC(+) rearrangement, targeted as either simple hit (25%) or complex hits (n=75%) including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. Results were statistically highly concordant in matched primary and relapsed biopsies (n = 45). Compared to the MYC(-) DLBCL patients, the MYC(+) DLBCL patients presented with a more elevated lactico-deshydrogenase level (P = .0006) and a more advanced age adjusted international prognostic index (P = .0039). The 4-year PFS and OS were significantly lower in the MYC(+) DLBCL patients than those in the MYC(-) DLBCL patients, with rates of 18% vs 42% (P = .0322), and of 29% vs 62% (P = .0113), respectively. Type of treatment, R-DHAP or R-ICE, had no impact on survivals, with 4-year PFS rates of 17% vs 19% and 4-year OS rates of 26% vs 31%. In conclusion, MYC rearrangement is an early event in DLBCL. MYC(+) DLBCL patients have a significant inferior prognosis than MYC(-) DLBCL patients. Their outcome was not influenced by the proposed salvage therapy.
authors.affiliation: Hematologie biologique, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), 1 Ave. Claude Vellefaux, Paris, France.
authors.forename: Wendy
authors.initials: W
authors.lastname: Cuccuini
authors.forename: Josette
authors.initials: J
authors.lastname: Briere
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mounier
authors.forename: Hans-Ullrich
authors.initials: HU
authors.lastname: Voelker
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Christer
authors.initials: C
authors.lastname: Sundstrom
authors.forename: Sergio
authors.initials: S
authors.lastname: Cogliatti
authors.forename: Edouard
authors.initials: E
authors.lastname: Hirchaud
authors.forename: Loic
authors.initials: L
authors.lastname: Ysebaert
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.forename: Jean
authors.initials: J
authors.lastname: Soulier
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Remi
authors.initials: R
authors.lastname: Houlgatte
authors.forename: Christian
authors.initials: C
authors.lastname: Gisselbrecht
authors.forename: Catherine
authors.initials: C
authors.lastname: Thieblemont
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016259:Genes, myc / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007167:Immunotherapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011034:Podophyllotoxin / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D016879:Salvage Therapy; D014182:Transplantation, Autologous; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D000069283:Rituximab; D005047:Etoposide; D003907:Dexamethasone; D011034:Podophyllotoxin; D002945:Cisplatin; D008558:Melphalan; D002330:Carmustine; D007069:Ifosfamide