title: Rituximab induces effective clearance of minimal residual disease in molecular relapses of mantle cell lymphoma.
abstract: Molecular remission (MR) is associated with improved outcome in mantle cell lymphoma (MCL). If MR is not achieved, patients are at high risk of relapse. We retrospectively describe the molecular and clinical follow-ups of 4 patients with molecular relapses (M-rels) who were treated with rituximab. The 4 patients received rituximab-supplemented, high-dose sequential chemotherapy and autologous stem cell transplantation as induction treatment and achieved clinical remission and MR. M-rel was defined as polymerase chain reaction (PCR) positivity in 2 consecutive samples in the absence of clinical relapse. M-rels occurred at 3, 6, 39, and 52 months and were always confirmed by direct sequencing of the clonal rearrangement. Minimal residual disease was monitored by qualitative and real-time quantitative PCR. All patients received 4 courses of rituximab, with 2 additional infusions if PCR positivity remained. After 4-6 courses of rituximab, all patients re-entered MR. No clinical relapses were recorded at 3, 6, 18, and 62 months from treatment, although 1 patient had a second M-rel that was sensitive to rituximab. Our results indicate that rituximab is active against residual MCL cells and suggest that molecularly tailored maintenance therapy needs to be investigated in clinical trials.
authors.affiliation: Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Torino, Italy. marco.ladetto@unito.it
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Michele
authors.initials: M
authors.lastname: Magni
authors.forename: Gloria
authors.initials: G
authors.lastname: Pagliano
authors.forename: Federica
authors.initials: F
authors.lastname: De Marco
authors.forename: Daniela
authors.initials: D
authors.lastname: Drandi
authors.forename: Irene
authors.initials: I
authors.lastname: Ricca
authors.forename: Monica
authors.initials: M
authors.lastname: Astolfi
authors.forename: Paola
authors.initials: P
authors.lastname: Matteucci
authors.forename: Anna
authors.initials: A
authors.lastname: Guidetti
authors.forename: Barbara
authors.initials: B
authors.lastname: Mantoan
authors.forename: Chiara Lobetti
authors.initials: CL
authors.lastname: Bodoni
authors.forename: Manuela
authors.initials: M
authors.lastname: Zanni
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics / Q000648:ultrastructure; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics / Q000648:ultrastructure; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004341:Drug Evaluation; D005500:Follow-Up Studies; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D018365:Neoplasm, Residual; D036102:Peripheral Blood Stem Cell Transplantation; D016133:Polymerase Chain Reaction; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D000069283:Rituximab; D016879:Salvage Therapy; D014178:Translocation, Genetic; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007143:Immunoglobulin Heavy Chains; D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D008558:Melphalan; D011241:Prednisone