Therapy for chronic myelogenous leukemia with marrow transplantation

Abstract

Chronic myelogenous leukemia is a lethal disease of the hematopoietic stem cell. Marrow transplant from an HLA-matched sibling donor can cure some patients with chronic myelogenous leukemia. Best results are observed when patients receive transplants early in chronic phase. The advantages of delaying marrow transplantation for a trial of interferon-alpha are questionable if a suitable matched related donor is available. The high incidence of relapse following T-lymphocyte-depleted marrow transplantation for chronic myelogenous leukemia emphasizes the existence of dormant, malignant clones that persist after ablative therapy. The presence of very small numbers of bcr-abl-positive hematopoietic cells after marrow transplantation can be detected by sensitive molecular genetic techniques and does not always predict hematologic relapse. Successful treatment of hematologic relapse after marrow transplantation can result from treatment with interferon-alpha, donor buffy coat cells, or second transplantation. HLA phenotypically matched and, in some cases, class I HLA antigen mismatched unrelated donors can be used successfully for marrow transplantation. Complications include an increased incidence of graft failure and graft-versus-host disease. Younger patients undergoing transplantation early in the disease course fare best. Preliminary results suggest that autologous marrow transplantation can induce complete hematologic and cytogenetic remission and may prolong survival in some cases. Strategies are being developed to obtain benign primitive progenitors suitable for autologous marrow transplantation by positive selection and to develop further posttransplantation antileukemic cell therapy to be used as an adjunct to autologous marrow transplantation for chronic myelogenous leukemia.