Gentler Chemotherapy Before Blood Stem Cell Transplant Causes Long-Term Complete Remission in Relapsed Follicular Lymphoma Patients
Treating relapsed follicular lymphoma patients with a milder chemotherapy regimen before they receive a blood stem cell transplant from a donor resulted in long-term complete remission for 45 of 47 patients in a clinical trial, researchers at The University of Texas M. D. Anderson Cancer Center report at the 49th annual meeting of the American Society of Hematology Meeting in Atlanta.
The two patients who had relapsed after the treatment regained a complete response after additional therapy.
"Our results show that this approach may actually be curative of follicular lymphoma," says lead author Issa Khouri, M.D., professor in M. D. Anderson's Department of Stem Cell Transplantation. "No other treatments produce this type of response."
The traditional treatment before receiving a matched stem cell donation consists of higher-dose chemotherapy that kills the lymphoma cells and shuts down the patient's own blood-producing stem cells – a process called myeloablation. While waiting for the donor's stem cells to engraft in the bone marrow and to begin producing blood, patients are vulnerable to infection, bleeding, and anemia.
Early research by Khouri and colleagues indicated that using a nonmyeloablative chemotherapy approach 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, a process called graft-vs.-lymphoma immunity.
"Our early results were encouraging. But with follicular lymphoma you need a long follow-up to see if the results hold," Khouri says. "This disease tends to recur later on, sometimes years after chemotherapy."
All patients in the present trial have been followed for at least five years, some for up to nine years. Trial patients had received 2 to 7 different chemotherapy regimens. Eight had received transplants of their own stem cells. At transplantation, 29 were in partial remission and 18 were in complete remission.
All 47 achieved complete remission after receiving matched blood stem cells from donors. One patient relapsed at 18 months. After receiving a donor lymphocyte infusion, the patient began a continuous complete response at 24 months. The other patient relapsed at 20 months and was found to have graft failure. Since treatment with rituximab, this patient has been in complete remission for four years.
Seven patients died during the trial, none from follicular lymphoma, Khouri notes. The 40 remaining patients all remain in remission. Overall survival at six years is 85% and current progression-free survival is 83%.
Acute graft-vs.-host disease (GVHD) arose in 11% of patients. Another 51% had chronic graft-vs.-host disease. GVHD was treated with immunosuppressive therapy. Khouri notes that only five patients in the study group remain on immunosuppressive therapy.
Long-term follow-up also allowed researchers to thoroughly gauge side effects, or toxicity, of the non-myeloablative approach. "It reduces toxicity significantly," Khouri says. "Even elderly patients can have this done."
Patients received fludarabine, cyclophosphamide and rituximab for three days before transplantation. Tacrolimus and methotrexate were used to prevent graft-vs.-host disease.
Follicular lymphoma is a Non-Hodgkin lymphoma, with about 12,000 new cases diagnosed annually.
Co-authors with Khouri are Rima M. Saliba, Martin Korbling, Chitra Hosing, Luis Fayad, Ming S. Lee, Felipe Samaniego, Barry I. Samuels, Daniel Couriel, Fredrick Hagemeister, Peter McLaughlin and Richard Champlin, all of M. D. Anderson. 12/10/07