Phase II of Immunochemotherapy, in Vivo Purging, PBSC Mobilization and Autotransplant in Patients With Relapsed or Refractory Follicular Lymphoma
Autologous stem cell transplantation has been shown effective in the long-term control of
follicular lymphoma. Lymphoma, however, can progress after high-dose treatments. Lymphoma
cells have been proved to contaminate bone marrow and peripheral blood stem cells (PBSC)
collections and may contribute to relapse after autotransplant. The presence in peripheral
blood and marrow of PCR-detectable cells bearing the bcl-2 rearrangement appeared to be a
surrogate marker of disease and the achievement of a bcl-2 negative status is associated
with a lower risk of recurrence. Several methods have been attempted to abolish graft
contamination: in vitro treatment with cytotoxic agents, in vitro treatment with anti-B-cell
monoclonal antibodies and complement, immunomagnetic beads, positive selection of CD34+
cells. All these techniques usually produce loss of cells, are time-consuming and expensive,
and neoplastic depletion is often partial with residual polymerase chain reaction
(PCR)-positive cells in the graft.
In the last years the chimeric anti-CD20 monoclonal antibody Rituximab has been shown to be
an effective therapeutic option for low-grade lymphoma. Owing to the different mechanism of
action, the synergism with cytotoxic agents, and the non-overlapping toxicity, Rituximab is
an ideal drug for combination with chemotherapy. On this basis, Rituximab has been used
during mobilisation procedures as a tool to obtain in vivo purging and collection of
lymphoma-free progenitor cells. In addition, several studies have demonstrated that the
efficiency of peripheral blood stem cells (PBSC) harvested is not adversely affected by
Rituximab and that engraftment and all parameters of hematopoietic recovery are not
compromised. The incorporation of Rituximab into sequential high-dose therapy programs
produced high rates of clinical and molecular remission in patients with indolent lymphoma,
indicating that the antibody has an additive effect on chemotherapy.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
PFS is calculated according to the Kaplan-Meier estimator. The observation time of each subject is defined as the time from entry into the study until lymphoma progression or death as a result of any cause whichever occurs first. The 5-year PFS is the estimated cumulative probability of surviving at least 5 years without progression.
every 3 months for the first year after autotransplant and every 6 months after the first year of follow up
Mario Lazzarino, M.D.
Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health