title: Rapid and sustained clearance of circulating lymphoma cells after chemotherapy plus rituximab: clinical significance of quantitative t(14;18) PCR monitoring in advanced stage follicular lymphoma patients.
abstract: This study of first-line treatment in advanced-stage follicular lymphoma patients analysed the effects of MCP (mitoxantrone, chlorambucil and prednisolone) chemotherapy alone or in combination with rituximab (R-MCP) on circulating lymphoma cells (CLC) and assessed the prognostic value of a quantitative monitoring of CLC. CLC numbers were determined by quantitative polymerase chain reaction (PCR) for the t(14;18)-translocation or by allele-specific PCR for rearranged immunoglobulin heavy chain genes. We analysed blood samples from 43 patients treated in a randomized trial comparing eight cycles of MCP versus R-MCP. Clearance of CLC at the end of therapy was achieved in 21/25 patients (84%) treated with R-MCP compared with 0/18 after MCP alone (P < 0.0001). A > or = 2 log CLC reduction was associated with a favourable clinical response (P = 0.0004) and prolonged event-free survival (P = 0.02). In R-MCP patients, stable CLC numbers or consistently PCR-negative blood samples were associated with a continuing clinical remission whereas in two patients a relapse was preceded by a > or = 2 log CLC increase. This study demonstrated that R-MCP led to a rapid and sustained eradication of CLC and a > or = 2 log CLC reduction was associated with a superior quality and duration of the clinical response.
authors.affiliation: Hämatologie und Onkologie-Transplantationszentrum, Universitätsklinikum Greifswald, Greifswald, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Hirt
authors.forename: Frank
authors.initials: F
authors.lastname: Schüler
authors.forename: Thomas
authors.initials: T
authors.lastname: Kiefer
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schwenke
authors.forename: Antje
authors.initials: A
authors.lastname: Haas
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Sabine
authors.initials: S
authors.lastname: Neser
authors.forename: Michael
authors.initials: M
authors.lastname: Assmann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Srock
authors.forename: Robert
authors.initials: R
authors.lastname: Rohrberg
authors.forename: Klaus
authors.initials: K
authors.lastname: Dachselt
authors.forename: Malte
authors.initials: M
authors.lastname: Leithäuser
authors.forename: Charles S
authors.initials: CS
authors.lastname: Rabkin
authors.forename: Michael
authors.initials: M
authors.lastname: Herold
authors.forename: Gottfried
authors.initials: G
authors.lastname: Dölken
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002699:Chlorambucil / Q000627:therapeutic use; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use; D018365:Neoplasm, Residual; D009360:Neoplastic Cells, Circulating / Q000187:drug effects*; D016133:Polymerase Chain Reaction / Q000379:methods; D011239:Prednisolone / Q000627:therapeutic use; D011379:Prognosis; D012074:Remission Induction; D000069283:Rituximab; D016019:Survival Analysis; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D002699:Chlorambucil; D000069283:Rituximab; D011239:Prednisolone; D008942:Mitoxantrone