title: Immunochemotherapy with in vivo purging and autotransplant induces long clinical and molecular remission in advanced relapsed and refractory follicular lymphoma.
abstract: BACKGROUND
  To evaluate the clinical outcome of patients with relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and high-dose therapy with autotransplant.
  
  
  METHODS
  Sixty-four patients were enrolled in the trial. Primary end point was progression-free survival (PFS). Secondary end points were the in vivo purging effect on stem-cell harvest and the impact of molecular response on the outcome.
  
  
  RESULTS
  At enrollment, 59% of patients were PCR+ for bcl-2 rearrangement in bone marrow (PCR-informative). After the immunochemotherapy, before mobilization, 97% obtained complete response or partial response and 87% of patients informative for bcl-2 were molecularly negative. Sixty-one patients proceeded to in vivo purging and peripheral blood stem cell (PBSC) mobilization with rituximab and high-dose AraC. The median number of CD34+ cells collected was 16.6 x 10(6)/kg. Of 33 PCR-informative patients, the harvests resulted in PCR- in all. Fifty-eight patients received high-dose therapy and autotransplant of in vivo purged PBSC. After a median follow-up of 3.5 years, 41 patients are in complete remission. Five-year PFS is 59%.
  
  
  CONCLUSIONS
  This study demonstrates that patients with advanced relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and autotransplant may obtain long-lasting PFS. In bcl-2-positive patients, in vivo purging allows the harvest of lymphoma-free PBSC. Absence of the bcl-2 rearrangement after autotransplant is associated with persistent clinical remission.
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia. Electronic address: luca.arcaini@unipv.it.
authors.forename: L
authors.initials: L
authors.lastname: Arcaini
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: F
authors.initials: F
authors.lastname: Montanari
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: E P
authors.initials: EP
authors.lastname: Alessandrino
authors.affiliation: Division of Hematology, Ospedali Civili, Brescia.
authors.forename: A
authors.initials: A
authors.lastname: Tucci
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: E
authors.initials: E
authors.lastname: Brusamolino
authors.affiliation: Division of Hematology, Niguarda Ca'Granda Hospital, Milano.
authors.forename: L
authors.initials: L
authors.lastname: Gargantini
authors.affiliation: Division of Hematology, Niguarda Ca'Granda Hospital, Milano.
authors.forename: R
authors.initials: R
authors.lastname: Cairoli
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: P
authors.initials: P
authors.lastname: Bernasconi
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: F
authors.initials: F
authors.lastname: Passamonti
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: M
authors.initials: M
authors.lastname: Bonfichi
authors.affiliation: Division of Hematology, Ospedale S. Camillo, Roma, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Zoli
authors.affiliation: Division of Hematology, Ospedali Civili, Brescia.
authors.forename: C
authors.initials: C
authors.lastname: Bottelli
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: S
authors.initials: S
authors.lastname: Calatroni
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: D
authors.initials: D
authors.lastname: Troletti
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: M
authors.initials: M
authors.lastname: Merli
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: C
authors.initials: C
authors.lastname: Pascutto
authors.affiliation: Division of Hematology, Ospedale S. Camillo, Roma, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Majolino
authors.affiliation: Division of Hematology, Ospedali Civili, Brescia.
authors.forename: G
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Division of Hematology, Niguarda Ca'Granda Hospital, Milano.
authors.forename: E
authors.initials: E
authors.lastname: Morra
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
authors.forename: M
authors.initials: M
authors.lastname: Lazzarino
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000378:metabolism; D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D016465:Bone Marrow Purging / Q000379:methods*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D019254:Genes, bcl-2; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D036102:Peripheral Blood Stem Cell Transplantation; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018952:Antigens, CD34; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D003561:Cytarabine; D001761:Bleomycin; D016179:Granulocyte Colony-Stimulating Factor; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide