Bone marrow transplantation for acute leukemia: Recent advances and comparison with alternative therapies

Bone marrow transplantation is an effective therapy in patients with acute leukemia. High-dose chemotherapy with or without total body irradiation and allogeneic bone marrow transplantation is a more effective antileukemic treatment than chemotherapy. This approach is limited, however, by a relatively high risk of transplant-related complications, particularly graft rejection, GVHD, and interstitial pneumonitis. Autologous bone marrow transplantation avoids the problems of graft rejection and GVHD. It does, however, introduce a risk of reinfusing residual leukemia cells with the autologous bone marrow and absence of a possible graft-versus-leukemia effect associated with allogeneic transplants. Bone marrow transplantation is useful in AML. Syngeneic or allogeneic HLA-identical bone marrow transplantation is the preferred treatment for patients under age 45 to 50 who fail chemotherapy. Transplantation is also likely to be superior or comparable to chemotherapy for patients less than 20 to 30 years of age in first remission. Transplantation in older individuals in first remission is controversial; results are comparable to those achieved with postremission chemotherapy. Transplants from donors other than HLA-identical siblings must be considered investigational but may be a reasonable alternative in young individuals in first relapse or second remission. Autotransplants are difficult to evaluate critically but may be considered as investigational therapy for individuals in second or later remission for whom a suitable allogeneic donor is unavailable. Autotransplants in first remission should be restricted to controlled clinical trials because it is otherwise impossible to determine their efficacy. It is uncertain whether ex vivo treatment of the bone marrow to remove leukemia cells is necessary in the context of autotransplantation; again, controlled trials are required. Bone marrow transplantation from an HLA-identical sibling is effective in individuals with ALL who relapse despite chemotherapy. Patients undergoing transplantation while in second or later remission or in relapse have a survival rate superior to those treated with chemotherapy. One important and unresolved issue is whether patients with high-risk ALL should receive bone marrow transplants or intensive postremission chemotherapy while in first remission; controlled clinical trials are needed. Bone marrow transplants from donors other than HLA-identical siblings and autologous bone marrow transplants are investigational approaches that should be considered in selected young patients who fail despite chemotherapy. The efficacy of ex vivo treatment of autologous bone marrow with monoclonal antibodies to leukemia cells is likewise improving and should be addressed in controlled trials. These data indicate an important role for bone marrow transplantation in the therapy of the acute leukemias. These therapeutic recommendations are based on current results of both chemotherapy and transplantation. Advances in either field, such as the introduction of more effective antileukemic chemotherapy or approaches to prevent the major complications of bone marrow transplantation, GVHD and interstitial pneumonitis, would require a reevaluation.