High dose chemotherapy and autologous bone marrow transplantation in acute leukemias, malignant lymphomas and solid tumors

Twenty-three adult patients with end stage and/or poor prognosis malignancies (6 solid tumors, 6 malignant lymphomas, 11 acute leukemias) were treated by high dose chemotherapy, with (16 patients) or without (7 patients) reinfusion of cryopreserved autologous marrow. Eighteen patients were treated by the TACC regimen (cyclophosphamide 45 mg/kg days 1–4, ARA-C 100 mg/m² q 12 hr days 1–4, 6-thioguanine 100 mg/m² q 12 hr days 1–4, CCNU 200 mg/m² day 2) and others received high dose combination chemotherapy regimens designed specifically for their anticipated tumor sensitivity. Additional radiotherapy was delivered in three cases. The results were analysed for toxicity, kinetics of recovery of hematopoiesis, and anti-tumor effects. All patients receiving cryopreserved marrow engrafted successfully and none died, although severe sepsis occured in six cases. In contrast, of the seven patients who did not receive cryopreserved marrow following the TACC regimen, three died from aplasia on days 15, 24 and 33. Recovery of leukocytes (WBC) and platelets in peripheral blood occurred twice as fast in patients with cryopreserved marrow: patients with solid tumors and malignant lymphomas recovered a WBC count of 1000/mm³ and a platelet count of 50,000/mm³ on day 11, regardless of the nature of the high dose therapy. Patients with acute leukemia had slightly delayed kinetics with recovery of leukocytes (>1000/mm³) and platelets (>50,000/mm³) occurring on day 18. Five of the six patients with solid tumors had a partial response (PR) on high dose therapy. Two patients with Hodgkin's disease achieved a complete remission, but the duration of the response was short (6 and 14 weeks). All four patients with non-Hodgkin's lymphomas went into complete remission (CR) and have remained free of disease without maintenance therapy for prolonged periods. All four patients with acute leukemias who received cryopreserved marrow went into complete remission and the duration of this CR paralleled the duration of the initial CR at the beginning of which the marrow had been harvested. One patient (AML) is still in CR 32 months after high dose therapy + autologous bone marrow transplantation (ABMT). Of the seven acute leukemia patients who did not receive cryopreserved marrow, only one had a CR of very short duration (1 month), and persisting, massive leukemic infiltration was demonstrated in five. These results demonstrate that ABMT is feasible in man and that it shortens the duration of aplasia following high dose therapy by about 50%. They also suggest that high dose therapy + ABMT should be included in the management of patients with acute leukemias, non-Hodgkin's lymphomas and some selected solid tumors.