Immunochemotherapy with in vivo purging and autotransplant induces long clinical and molecular remission in advanced relapsed and refractory follicular lymphoma

Ann Oncol. 2008 Jul;19(7):1331-1335. doi: 10.1093/annonc/mdn044. Epub 2008 Mar 15.

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.

Patients and 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%.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Anthracyclines / administration & dosage
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 / metabolism
  • Antigens, CD34 / analysis
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Bone Marrow Purging / methods*
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Disease Progression
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Female
  • Follow-Up Studies
  • Genes, bcl-2
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hematopoietic Stem Cell Mobilization
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunosuppressive Agents / administration & dosage
  • Kaplan-Meier Estimate
  • Lymphoma, Follicular / drug therapy
  • Lymphoma, Follicular / pathology
  • Lymphoma, Follicular / therapy*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peripheral Blood Stem Cell Transplantation*
  • Recurrence
  • Remission Induction
  • Rituximab
  • Time Factors
  • Transplantation, Autologous
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Anthracyclines
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Antigens, CD34
  • Immunologic Factors
  • Immunosuppressive Agents
  • Cytarabine
  • Bleomycin
  • Granulocyte Colony-Stimulating Factor
  • Rituximab
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide

Supplementary concepts

  • VACO-B protocol