Chemotherapy Compared with Autologous or Allogeneic Bone Marrow Transplantation in the Management of Acute Myeloid Leukemia in First Remission
Reviewers: Kenneth Blank, MD
Source: New England Journal of Medicine [December 3, 1998] Vol. 339 No 23 p 1649
The majority of patients with acute myelogenous leukemia attain a complete remission after initial chemotherapy. The incorporation of high dose cytarabine to the post-remission chemotherapy regimen has improved five-year disease-free survival rates from 10 to 30 percent. A strategy to further increase the dose of chemotherapy involves the use of stem cell support in the form of a bone marrow transplant. Several studies have shown bone marrow transplant to be of benefit, but other reports have not confirmed this finding. The controversy over the use of bone marrow transplantation in patients with AML in remission has led to a large multi-institutional randomized study. The results of this study are reported in the December 3, 1998 issue of the New England Journal of Medicine.
Materials and Methods
Adult patients aged sixteen through fifty-five were randomly assigned to receive either high dose cytarabine or autologous (stem cells from the same patient) bone marrow transplantation after attaining a complete remission with induction chemotherapy. Patients with histocompatible siblings were registered to receive allogeneic (stem cells from a donor) bone marrow transplants. Induction chemotherapy consisted of two days of idarubicin and five days of cytarabine. Preparative regimens for both the autologous and allogeneic transplant groups were oral busulfan and intravenous cyclophosphamide.
Eight hundred and eight patients entered the study and 740 were eligible for induction therapy. The main reasons for ineligibility were incorrect diagnosis and missing data. Of these 740 patients, 70 percent (518) achieved a complete remission. One hundred and 72 patients were not randomized or assigned to allogeneic transplant for a variety or reasons including patient non-compliance, persistent medical problems and relapse before randomization, leaving 346 patients for randomization. Of these 346, 113 had a histocompatible sibling and were assigned to receive an allogeneic transplant. The remaining patients were randomized to either high dose cytarabine or autologous bone marrow transplant.
The four-year survival rate for all 740 patients was 35 percent with a median survival of nineteen months. With a median follow-up of four years, there was a significant survival advantage to high dose cytarabine when compared to either of the transplant arms. There was no difference in survival between the patients receiving allogeneic or autologous transplant. Disease-free survival was similar for all patients when analyzed by intent to treat.
The authors conclude that a course of high dose cytarabine following complete remission provides equivalent disease-free survival and better overall survival than either autologous or allogeneic bone marrow transplant.