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.
Publication types
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Multicenter Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antibodies, Monoclonal, Murine-Derived / administration & dosage*
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Antibodies, Monoclonal, Murine-Derived / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Carmustine / administration & dosage
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Carmustine / adverse effects
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Chemotherapy, Adjuvant
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Cisplatin / administration & dosage
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Cisplatin / adverse effects
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Combined Modality Therapy
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Cytarabine / administration & dosage
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Cytarabine / adverse effects
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Dexamethasone / administration & dosage
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Dexamethasone / adverse effects
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Etoposide / administration & dosage
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Etoposide / adverse effects
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Female
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Genes, myc / physiology
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Hematopoietic Stem Cell Transplantation* / methods
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Humans
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Ifosfamide / administration & dosage
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Ifosfamide / adverse effects
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Immunotherapy
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Lymphoma, Large B-Cell, Diffuse / drug therapy
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Lymphoma, Large B-Cell, Diffuse / genetics
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Lymphoma, Large B-Cell, Diffuse / mortality
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Lymphoma, Large B-Cell, Diffuse / therapy*
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Male
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Melphalan / administration & dosage
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Melphalan / adverse effects
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Middle Aged
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Podophyllotoxin / administration & dosage
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Podophyllotoxin / adverse effects
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Rituximab
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Salvage Therapy
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Transplantation, Autologous
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Treatment Failure
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Young Adult
Substances
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Antibodies, Monoclonal, Murine-Derived
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Cytarabine
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Rituximab
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Etoposide
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Dexamethasone
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Podophyllotoxin
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Cisplatin
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Melphalan
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Carmustine
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Ifosfamide
Supplementary concepts
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BEAM protocol
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DHAP protocol
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ICE protocol 1