Treatment of Acute Leukemia in Remission by Bone Marrow Transplantation

Summary

Before 1975 only patients with chemotherapy-refractory acute leukemia were treated by marrow transplantation. The preparative regimen developed in Seattle consisted of cyclophosphamide (60 mg/kg on each of 2 successive days) followed 2-3 days later by 1,000 rad total body irradiation from two opposing cobalt sources and a marrow transplant from an HLA-identical sibling. Of the first 100 patients, 13 are alive in unmaintained remission 5.5–10 years after transplantation with functioning marrow grafts. In this initial series of patients leukemic recurrence was one of the major problems. Attempts to reduce recurrent leukemia by the use of more aggressive antileukemic regimens before transplantation were unsuccessful. However, the fact that a number of “end-stage” patients had apparently been cured of their disease encouraged the Seattle team to begin a study in early 1976 of acute leukemia patients transplanted in remission. Twenty-two patients with acute lymphoblastic leukemia were transplanted in second, third, or subsequent remission and eight (35%) are now in unmaintained remission 2.5–4.5 years later. Recurrent leukemia was the cause of death for 11 patients in the acute lymphoblastic leukemia group. Twelve of the first 19 patients with acute nonlymphoblastic leukemia grafted in first remission are now alive and well in unmaintained remission 2–4 years after transplantation. At present 48 patients have been included in the study and 31 (65%) are living in remission. Only one of the 48 patients has had a recurrence of leukemia. The principal causes of death were graft-versus-host disease and interstitial pneumonia.

Marrow transplantation for patients with chronic myelogenous leukemia in blast crisis has resulted in one unmaintained remission surviving now, at 4.5 years, among six patients with syngeneic grafts and four long-term survivors (8, 15, 27, and 31 months) among 22 patients with allogeneic grafts. Three of four patients with chronic myelogenous leukemia in chronic phase given syngeneic transplants are now in remission with lack of Philadelphia chromosome at 3–4 years, while one had reappearance of the Philadelphia chromosome at 2.5 years and is now surviving in the chronic phase.

This investigation was supported by grant numbers CA 18029, CA 15704, and CA 18221, awarded by the National Cancer Institute, DHEW