High dose combination chemotherapy (TACC) with and without autologous bone marrow transplantation for the treatment of acute leukaemia and other malignant diseases: Kinetics of recovery of haemopoiesis. A preliminary study of 12 cases

Abstract

Twelve patients received a high dose combination chemotherapy regimen (TACC) consisting of cyclophosphamide 45 mg/kg i.v. day 1–4, ARA-C 100 mg/m 2 i.v. every 12 hr day 1–4, 6 thioguanine 100 mg/m 2 by mouth every 12 hr day 1–4, CCNU 200 mg/m 2 by mouth day 2. Of these 12 patients, 8 received cryopreserved autologous marrow and 4 received only supportive care. The patients were divided into 3 groups: • —Group 1 consisted of 4 patients with solid tumours without bone marrow involvement. • —Group 2 consisted of 4 patients with drug resistant acute leukaemia in relapse. • —Patients in groups 1 and 2 received the TACC regimen followed by the infusion of cryopreserved marrow harvested at a time when bone marrow examination was normal. In these two groups, the doses of bone marrow infused ranged from 0.5 to 2.2 × 10 8 nucleated bone marrow cells/ kg and had been preserved for periods up to 18 months. Recovery to a WBC count of 1000/mm 3 occurred on days 12–19 (median day 17) and recovery to a platelet count of 50,000/mm 3 occurred on days 9–28 (median day 15). In group 1, one patient with Hodgkin's disease went into complete remission. The 3 other patients went into partial remission. In group 2, all 4 patients with acute leukaemia went into complete remission. • —Group 3 consisted of 4 patients with drug resistant acute leukaemia. These patients received the same high dose combination chemotherapy regimen without cryopreserved marrow. One patient went into a complete remission with a recovery to a WBC count of 1000/mm 3 on day 30 and recovery to a platelet count of 50,000/mm 3 on day 35. This patient relapsed on day 69. In 2 other patients, recovery to a WBC count of 1000/mm 3 occurred on days 27 and 28 with 77% and 9% residual circulating leukaemic cells. The last patient died on day 15 with severe hypoplasia and persisting massive visceral leukaemic infiltration. • —Groups 1 + 2 (infusion of cryopreserved marrow) were compared to group 3 (no infusion of cryopreserved marrow), and group 2 was compared to group 3 (acute leukaemias). The results of this study support the following statements. 1. 1. Following high dose combination chemotherapy (TACC), the reinfusion of cryopreserved autologous marrow is beneficial in shortening by about 50% the duration of the aplasia, in all patients. 2. 2. The TACC high dose combination chemotherapy without autologous bone marrow transplantation, ◦ —does not induce irreversible aplasia in leukaemic patients, ◦ —does not eradicate leukaemia.