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In Vivo Purging and Adjuvant Immunotherapy With Rituximab During PBSC Transplant For NHL

In Vivo Purging and Adjuvant Immunotherapy With Rituximab During PBSC Transplant For NHL

Contamination of the peripheral blood stem-cell (PBSC) graft with lymphoma and residual disease remaining in the patient after high-dose therapy are two potential causes of relapse after autologous transplantation. Using a tumor-specific monoclonal antibody may be one way to purge the stem-cell graft in vivo and increase the efficacy of the preparative regimen. Rituximab (Rituxan) is an IgG1 kappa chimeric mouse/human antibody containing murine light- and heavy-chain variable regions and human gamma 1 heavy-chain and light-chain constant regions. The antibody reacts specifically with the CD20 antigen found on the surface of malignant and normal B-cells.

We are conducting a trial of rituximab as an in vivo purging agent and as posttransplant adjuvant immunotherapy. Patients withNHL receive 375 mg/m² of rituximab on day 1 of mobilization, followed by 2.5 g/m² of cyclophosphamide (Cytoxan, Neosar) on day 4, and 10 µg/kg of granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) starting on day 5. Stem cells are collected using a high-volume apheresis procedure, with a goal of 5 × 106 CD34/kg. The preparative regimen consists of either cyclophosphamide and total-body irradiation or busulfan (Myleran) and cyclophosphamide. Granulocyte colony-stimulating factor is used posttransplant. One dose of rituximab is given posttransplant 7 days after platelets reach 20,000/mm³.

A total of 19 patients (11 males, 8 females), median age 50 years (range, 32-65 years), have started therapy. Diagnoses include 6 follicular center cell lymphomas, 6 mantle cell lymphomas, 4 small lymphocytic/chronic lymphocytic leukemias, 2 cases of Richter’s transformation, and 1 Waldenström’s macroglobulinemia.

Of the 19 patients, 18 patients were successfully mobilized, with a threshold of 2.0 × 106 CD34/kg (median, 1.36 × 107 CD34/kg; range 2.51 × 106-5.95 × 107 CD34/kg). No CD20+ cells were detectable by flow cytometry in any of the grafts. Of 13 patients who have reached ³ day 30, the median day to reach ³ 1,000 ANC was day 10 (range, days 7-15) and the median day to achieve unsupported platelets ³ 20,000/mm³ was day 9 (range, days 3-14). Toxicities include one patient who developed pancytopenia starting at approximately day 30, with subsequent slow recovery, and idiopathic thrombocytopenic purpura in one patient that rapidly responded to steroids.

CONCLUSION: We conclude that this is a well-tolerated regimen that successfully depletes stem-cell grafts of CD20+ cells, provides rapid engraftment, and is associated with little added toxicity. Accrual and follow-up continue.

 Click here for Dr. Bruce Cheson’s commentary on this abstract.

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