Transplant Better With Milder Chemotherapy
CancerWise - March 2008
Using a lower-dose chemotherapy before a blood stem cell transplant from a donor may cause fewer side effects and better outcomes than standard high-dose therapy for patients with relapsed follicular lymphoma, a new study reports.
Significance of results
"No other treatments produce this type of response," says the clinical trial’s lead author Issa Khouri, M.D., a professor in M. D. Anderson's Department of Stem Cell Transplantation and Cellular Therapy. Khouri presented the results in December at the American Society of Hematology meeting in Atlanta.
The traditional treatment for patients with follicular lymphoma, a type of non-Hodgkin's lymphoma, is chemotherapy, but the disease often returns. Patients who relapse are treated with high-dose chemotherapy, which causes serious side effects. They then receive an allogeneic stem cell transplant (from a donor).
The high-dose chemotherapy kills the lymphoma cells and shuts down the patient's own blood-producing stem cells. While waiting for the donor's stem cells to engraft (come together) in the bone marrow and to begin producing healthy blood cells, patients are vulnerable to infection, bleeding and anemia.
"Replacing high-dose chemotherapy with low-dose chemotherapy in preparation of allogeneic stem cell transplant resulted in remission for all of the 47 patients in the study," Khouri says.
Only two of the 47 patients relapsed, one at 18 months and the other at 20 months. A second remission was brought about for both after additional therapy that included a donor lymphocyte infusion (the infusion of a type of white blood cell from the stem cell donor) and Rituximab (Rituxan®).
"In follicular lymphoma, you need a long follow-up to see if results hold," Khouri says. "In this study, patients have been followed for at least five years, some for up to nine years. Overall survival at six years was 85% and current progression-free survival is 83%."
Patients in the trial will continue to be followed.
Seven patients died during the trial, none from follicular lymphoma, Khouri says. The 40 remaining patients continue to be in remission.
Long-term follow-up of the patients in this study allowed researchers to thoroughly gauge side effects, or toxicity. "Using the milder chemotherapy reduces toxicity significantly," Khouri says.
One of the most severe side effects in allogeneic transplantations has historically included acute graft-versus-host disease (GVHD). GVHD occurs when a donor’s T cells (cells that activate the immune system) attack healthy cells in a stem cell transplant recipient’s body.
"GVHD used to occur in 40% to 60% of patients who received allogeneic transplantations after high-dose chemotherapy," Khouri says. "With the low-dose chemotherapy, the incidence of acute GVHD occurred in only 11% of patients.
Khouri notes that only five patients in the study group remain on immunosuppressive therapy.
Patients received the chemotherapy drugs fludarabine phosphate, cyclophosphamide (Cytoxan®) and rituximab for three days before transplantation. Tacrolimus (Protopic® ointment) and methotrexate (Rheumatrex®, Trexall®) were used to prevent GVHD.
Early research by Khouri and colleagues indicated that using a chemotherapy that does not shut down the patient's stem cells could control the lymphoma while sparing patients the side effects of high-dose chemotherapy. The transplanted blood stem cells launch an immune system attack on the lymphoma.
"This is the most successful treatment available for patients with recurrent follicular lymphoma, and physicians in the community should be encouraged to refer those patients with recurrent follicular lymphoma to M. D. Anderson to be evaluated for this strategy," Khouri says.
Khouri also stated that patients up to 75 years of age are eligible for this trial.
For more information about the study, contact Debra Major at 713-792-8750.
– Adapted by Darcy De Leon from an M. D. Anderson news release
M. D. Anderson resources:
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