Immunochemotherapy with in vivo purging and autotransplant induces long clinical and molecular remission in advanced relapsed and refractory follicular lymphoma.
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.
Arcaini
L
L
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia. Electronic address: luca.arcaini@unipv.it.
Montanari
F
F
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
Alessandrino
E P
EP
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
Tucci
A
A
Division of Hematology, Ospedali Civili, Brescia.
Brusamolino
E
E
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
Gargantini
L
L
Division of Hematology, Niguarda Ca'Granda Hospital, Milano.
Cairoli
R
R
Division of Hematology, Niguarda Ca'Granda Hospital, Milano.
Bernasconi
P
P
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
Passamonti
F
F
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
Bonfichi
M
M
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
Zoli
V
V
Division of Hematology, Ospedale S. Camillo, Roma, Italy.
Bottelli
C
C
Division of Hematology, Ospedali Civili, Brescia.
Calatroni
S
S
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
Troletti
D
D
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
Merli
M
M
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
Pascutto
C
C
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
Majolino
I
I
Division of Hematology, Ospedale S. Camillo, Roma, Italy.
Rossi
G
G
Division of Hematology, Ospedali Civili, Brescia.
Morra
E
E
Division of Hematology, Niguarda Ca'Granda Hospital, Milano.
Lazzarino
M
M
Division of Hematology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia.
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
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