A L Billett1, S E Sallan. 1. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
Abstract
INTRODUCTION: Chemotherapy alone is rarely curative for children with recurrent acute lymphoid leukemia (ALL). Although allogeneic bone marrow transplantation has been reported to provide disease-free survival rates of from 40 to 70%, its application is severely limited by the lack of sibling donors. The use of autologous bone marrow transplantation (ABMT) allows the application of therapy of comparable intensity to a larger number of patients. A potential problem associated with transplanting autologous marrow, the reinfusion of residual leukemic cells in the harvested marrow, can be addressed through purging. The most widely used purging techniques involve either immunologic or pharmacologic techniques. PATIENTS AND METHODS: Since 1980, the Dana-Farber Cancer Institute has had an active autologous bone marrow transplantation program for children with recurrent ALL. Sixty-six children underwent autologous marrow transplants with a conditioning regimen consisting of teniposide, cytarabine, cyclophosphamide, and total body irradiation. This was followed by infusion of autologous marrow purged with two monoclonal antibodies directed against CD9 and CD10 and complement. RESULTS: Twelve patients died of acute complications, 26 experienced relapse of ALL, one patient had acute myeloid leukemia 6 years after marrow transplant, and 27 remain in continuous complete remission. The event-free survival rate was 47% for patients with a first remission of at least 2 years, as compared with a rate of 10% for those with a shorter first remission. Since 1989, we have used a new conditioning regimen consisting of fractionated total body irradiation followed by high-dose etoposide and cyclophosphamide for patients with a short first remission. For the first 11 patients, the event-free survival rate is 61%. LITERATURE REVIEW: We reviewed reports of 552 patients with ALL who underwent ABMT at 17 centers. To our knowledge, only four series, including our own, were limited to pediatric patients. Some form of purging was used in 483 (87%) patients. Although conditioning regimens varied greatly, more than 80% of patients received at least total body irradiation and cyclophosphamide. Failure of engraftment was reported in only three patients. The rates of disease-free survival in these series clustered between 25-35%. The most common cause of treatment failure after ABMT was relapse, which occurred in 40-85% of patients. Early deaths from toxicity occurred in 5-21% of patients. Two studies attempted to compare the results of allogeneic and autologous bone marrow transplantation by using the same conditioning regimen for all. Neither series reported significant differences in overall survival.
INTRODUCTION: Chemotherapy alone is rarely curative for children with recurrent acute lymphoid leukemia (ALL). Although allogeneic bone marrow transplantation has been reported to provide disease-free survival rates of from 40 to 70%, its application is severely limited by the lack of sibling donors. The use of autologous bone marrow transplantation (ABMT) allows the application of therapy of comparable intensity to a larger number of patients. A potential problem associated with transplanting autologous marrow, the reinfusion of residual leukemic cells in the harvested marrow, can be addressed through purging. The most widely used purging techniques involve either immunologic or pharmacologic techniques. PATIENTS AND METHODS: Since 1980, the Dana-Farber Cancer Institute has had an active autologous bone marrow transplantation program for children with recurrent ALL. Sixty-six children underwent autologous marrow transplants with a conditioning regimen consisting of teniposide, cytarabine, cyclophosphamide, and total body irradiation. This was followed by infusion of autologous marrow purged with two monoclonal antibodies directed against CD9 and CD10 and complement. RESULTS: Twelve patients died of acute complications, 26 experienced relapse of ALL, one patient had acute myeloid leukemia 6 years after marrow transplant, and 27 remain in continuous complete remission. The event-free survival rate was 47% for patients with a first remission of at least 2 years, as compared with a rate of 10% for those with a shorter first remission. Since 1989, we have used a new conditioning regimen consisting of fractionated total body irradiation followed by high-dose etoposide and cyclophosphamide for patients with a short first remission. For the first 11 patients, the event-free survival rate is 61%. LITERATURE REVIEW: We reviewed reports of 552 patients with ALL who underwent ABMT at 17 centers. To our knowledge, only four series, including our own, were limited to pediatric patients. Some form of purging was used in 483 (87%) patients. Although conditioning regimens varied greatly, more than 80% of patients received at least total body irradiation and cyclophosphamide. Failure of engraftment was reported in only three patients. The rates of disease-free survival in these series clustered between 25-35%. The most common cause of treatment failure after ABMT was relapse, which occurred in 40-85% of patients. Early deaths from toxicity occurred in 5-21% of patients. Two studies attempted to compare the results of allogeneic and autologous bone marrow transplantation by using the same conditioning regimen for all. Neither series reported significant differences in overall survival.