Autologous peripheral blood stem-cell (PBSC)
transplantation may play an important role in the treatment of
indolent lymphomas, as well as aggressive lymphomas. Concern about
the contamination of the autologous graft with lymphoma remains, as
contamination may shorten disease-free survival.
Rituximab (Rituxan) used during stem cell mobilization is a promising
method for purging PBSCs of lymphoma in vivo. Similarly, when
administered following transplantation, this antibody may serve as
adjuvant immunotherapy. We are conducting trials with rituximab
during PBSC transplant for non-Hodgkins lymphoma. (NHL). The
purpose of these trials is to evaluate the safety and efficacy of in
vivo purging with rituximab. Tumor contamination of the PBSC graft is
being measured with lymphoma colony formation and/or polymerase chain
A total of 51 patients (32 males, 19 females) at a median age of 52
years (range, 32 to 67 years) have been accrued. Diagnoses included:
follicular (23 patients), mantle cell (10 patients), small
lymphocytic/chronic lymphocytic (13 patients), marginal zone (3
patients), and lymphoplasmacytic lymphomas (2 patients).
Patients received 375 mg/m² of rituximab on day 1 of
mobilization, followed by cyclophosphamide (Cytoxan, Neosar), 2.5 g/m²
on day 4, and either granulocyte-colony-stimulating factor (G-CSF
[Neupogen]), 10 µg/kg starting on day 5, or
granulocyte-macrophage colony-stimulating factor (GM-CSF [Leukine,
Prokine]), 10 µg/kg on days 5 to 11, and G-CSF ,10 mg/kg
starting on day 10 through the last day of apheresis, depending on
Stem cells were collected using a high-volume apheresis procedure.
The last 26 patients were CD34-selected for tumor depletion if ³
5× 106 CD34/kg were collected. The preparative
regimen consisted of either cyclophosphamide and total-body
irradiation or busulfan (Myleran) and cyclophosphamide in patients
who had received prior external irradiation. Following
transplantation, patients received one or four doses of rituximab,
depending on the protocol.In 46 of the 51 patients, stem cells were
successfully mobilized (median, 10.9 × 106 CD34/kg;
range, 2.24 × 106 to 59.5 × 106 CD34/ kg). Of
the 46 patients, 38 required only one high-volume apheresis.
A total of 19 grafts were CD34 selected. Of the 19 grafts, 17 were
lymphoma free in a clonogenic assay performed prior to CD34
selection, and 17 were lymphoma free following selection. Seven
recipients of unmanipulated grafts had lymphomas that were positive
for t(11;14) or t(14;18), and only one of these grafts was PCR
positive. Results of PCR analysis of CD34-selected grafts are
pending.Although follow-up is short, there has been little additional
toxicity and only 1 death in the 35 transplanted patients.
CONCLUSION: Although these results are preliminary, it appears that
rituximab may be an effective method for in vivo purging autologous
grafts of indolent lymphoma.