M. Flesch

Autologous bone marrow transplantation (ABMT) for acute leukaemia in complete remission: a pilot study of 33 cases

Thirty‐three leukaemic patients in CR were treated by high‐dose therapy followed by ABMT: 18 of them had acute non‐lymphoblastic leukaemia (ANLL) in first remission (CR1) with a mean age of 23.7 years (3–44). All but one of them were conditioned with a polychemotherapy regimen including 6‐thioguanine, Ara‐C, CCNU, and cyclophosphamide. The marrow cells were purged by chemical means in 16 cases.

Intensive cytoreductive regimen and autologous bone marrow transplantation in leukemia. Present status and the future. A review

High-dose cytoreductive treatment followed by ABMT represents a new approach to the treatment of acute leukemia as an alternative when leukemic patients do not have HLA-identical donors. ABMT protocol seems to be a valuable treatment for AML if it is immediately employed after the remission obtained to consolidate the remission. For ALL adult patients, and so for poor prognosis ALL in children, intensive therapy with ABMT represents a new approach when conventional therapy has failed or failed to consolidate the remission. The results of ABMT in CML in the literature have been disappointing; the bone marrow could be collected during the course of the first chronic phase after hydroxyurea therapy or other treatment programs. In leukemia the ABMT approach will be more credible if the protocol includes in vitro immunologic or pharmacologic means to eliminate residual leukemic cells.

Autologous bone marrow transplantation for acute leukemia using transplant chemopurified with metabolite of oxazaphosphorines (ASTA Z 7557, INN mafosfamide)

SummaryThe contamination of autologous marrow with clonogenic tumor cells has been the main argument against ABMT in acute leukemia.In a preclinical study we evaluated an active cyclophosphamide derivative named “ASTA Z 7557”. We observed that the toxic effect of this drug on CFU-GM growth was dependent on nucleated cell concentration as well as on red blood cell contamination. The potency of the drug was in close relationship with the incubation temperature.The growth of leukemic CFU was inhibited with an ASTA Z dose higher than 30 μg/ml. In our system, beyond 40 μg/ml more than 95% of committed stem cells are destroyed.Fifteen patients had autotransplant because of AML for 10 patients and because of ALL for 5 patients (4 patients were grafted in relapse and 11 patients in remission).We demonstrated that the marrow take was possible although the inoculum is CFU-GM depleted.Five of the 10 AML patients are alive and remain disease-free at 45 +, 65 +, 190 +, 345+ and 570 + days from ABMT without any maintenance treatment. Four of the 5 ALL patients are alive, three of them in complete remission (404+, 110+, 250+ days).The number of patients reported in this clinical study was relatively small and more cases should be evaluated to be conclusive. Nevertheless the feasibility of chemopurified ABMT was demonstrated.

Marrow transplantation from HLA non-identical family donors for the treatment of leukaemia: a pilot study of 15 patients using additional immunosuppression and T-cell depletion

Fifteen patients with high‐risk leukaemia were given T‐cell depleted marrow transplants from HLA non‐identical related donors. They were treated with a combination of total body irradiation (TBI), high‐dose cytosine arabinoside (Ara‐C) and high‐dose melphalan in an attempt to prevent a host‐versus‐graft reaction. Antilymphocyte globulins were given prior to transplantation for additional immunosuppression to 13 patients and in‐vivo monoclonal antibody anti‐human LFA1 to two. Engraftment and chimaerism assessed by HLA typing were achieved in 14 patients. Seven developed acute graft‐versus‐host disease (two fatal), one failed to engraft. Six patients died in complete remission from cytomegalovirus (CMV) interstitial pneumonitis and three remain alive in complete remission 2, 3 and 13 months after transplant. We conclude that aggressive immunosuppression allows for sustained engraftment of T‐cell depleted HLA non‐identical marrow. The incidence and severity of GVHD are acceptable and CMV pneumonitis remains the major problem.