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

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Article
OncologyONCOLOGY Vol 13 No 3
Volume 13
Issue 3

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.

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.

Articles in this issue

WHO Declares Lymphatic Mapping to Be the Standard of Care for Melanoma
Rituximab: Phase II Retreatment Study in Patients With Low-Grade or Follicular Non-Hodgkin’s Lymphoma
Response Criteria for NHL: Importance of “Normal” Lymph Node Size and Correlations With Response
Chemotherapy Plus Radiation Improves Survival in Patients With Cervical Cancer
A Randomized Trial of Fludarabine, Mitoxantrone (FM) Versus Doxorubicin, Cyclophosphamide, Vindesine, Prednisone (CHEP) as First Line Treatment in Patients With Advanced Low-Grade Non-Hodgkin's Lymphoma: A Multicenter Study by GOELAMS Group
Navelbine Increased Elderly Lung Cancer Patients’ Survival
Fludarabine Versus Conventional CVP Chemotherapy in Newly C Diagnosed Patients With Stages III and IV Low-Grade Malignant Non-Hodgkin’s Lymphoma: Preliminary Results From a Prospective, Randomized Phase III Clinical Trial in 381 Patients
Multicenter, Phase III Study of Iodine-131 Tositumomab (Anti-B1 Antibody) for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin’s Lymphoma
T-Cell–Depleted Allogeneic Bone Marrow Transplant From HLA-Matched Sibling Donors for Non-Hodgkin’s Lymphoma
Consensus Statement on Prevention and Early Diagnosis of Lung Cancer
In Vivo Purging and Adjuvant Immunotherapy With Rituximab During PBSC Transplant For NHL
Fludarabine and Cyclophosphamide: A Highly Active and Well-Tolerated Regimen for Patients With Previously Untreated Indolent Lymphomas
Campath-1H Monoclonal Antibody in Therapy for Advanced Low-Grade Non-Hodgkin’s Lymphomas: A Phase II Study
AIDS Drugs Effective Against Most Common HIV Strain
Rituximab Therapy in Previously Treated Waldenström’s Macroglobulinemia: Preliminary Evidence of Activity
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