Low dose T-cell lymphocyte infusion combined with marrow T-cell depletion as prophylaxis of acute graft vs host disease for HLA identical sibling bone marrow transplantation.

T-cell depletion (TCD) of the bone marrow graft remains the most effective method to prevent severe graft versus host disease after allogeneic bone marrow transplantation. Early studies of HLA-identical sibling transplants showed that although T-cell depletion decreased GVHD, T-cell depleted transplants had higher risks of graft failure and leukemia relapse, leukemia free survival (LFS) was not improved compared to non-T-cell depleted transplants. In order to avoid graft failure and increased risk of relapse associated with this approach, we initiated a pilot study of T-cell depletion of the marrow graft combined with reinfusion of a fixed quantity of CD2+ peripheral blood T-cells. Depletion technique consisted in negative purging using CD2 and CD7 monoclonal antibodies (MoAbs) followed by rabbit complement cytolysis. This approach was associated with an intensified conditioning regimen using total body irradiation, high-dose cytosine arabinoside and melphalan (TAM) for all but one patient. Twenty-one patients were included with a mean age of 40 years. Only one acute severe Graft Versus Host Disease (GVHD) was observed and all patients engrafted. At 63 months, probability of survival is 42.86% with a relapse risk of 19.89%, two patients died from B-cell lymphoproliferative disease, seven other died from the procedure partially because of the use of the TAM as pretransplant regimen. This approach is being pursued by a gene therapy trial using herpes-simplex - 1 thymidine kinase gene expressing peripheral donor T-cells.

Allogeneic bone marrow transplantation for high-risk acute lymphoblastic leukemia in first remission: long-term results for 42 patients conditioned with an intensified regimen (TBI, high-dose Ara-C and melphalan).

Attempts to improve the efficacy of pretransplant conditioning regimens have been published, the potential of a better antileukemic effect being impaired by more frequent and severe toxicities. The efficacy of an intensified regimen, TAM (TBI, high-dose cytosine arabinoside and melphalan), is evaluated by analyzing long-term follow-up of a homogenous group of 42 high-risk ALL patients allografted in first CR. Age at time of BMT was 25.9 +/- 10.4 years (3-41). Twenty-two patients had more than three adverse prognostic factors. Ten patients had a Ph chromosome. Probability of overall survival was 45 +/- 9%, and for all surviving patients median follow-up time was 66 months. Event-free survival was 40 +/- 8% at 7 years after transplantation and the expected relapse rate reached 31%. Twenty-two deaths occurred, six after a relapse but 16 appeared to be directly due to the BMT procedure. None of the pretransplant characteristics significantly affected outcome after BMT. TAM appeared to be an efficient antileukemic therapy for conditioning high-risk ALL patients before allogeneic transplantation, but was still very toxic. The use of TAM in adult ALL patients in first CR is not recommended and the real role of intensified conditioning regimens remains to be demonstrated.

Prognostic factors for autologous bone marrow transplantation in acute leukaemia: a single centre study of 105 patients.

Since the treatment of leukaemia by autologous bone marrow transplantation is becoming increasingly frequent, a retrospective study was undertaken to ascertain factors influencing the evolution of the disease (death and relapse). Data were collected over a period of 11 years for 105 patients with acute leukaemia (60 lymphoid cases and 45 myeloid cases). Multivariate analysis by the Cox model was used to determine prognostic factors for survival and disease free survival (DFS). Overall survival for the entire population was 35% after 8 years while DFS was 33% after 3 years. The major prognostic criteria were granulocyte recovery time (p < 0.001 at 5 weeks) and platelet recovery time (p < 0.02 at 6 weeks). Patients conditioned by an association of polychemotherapy and total body irradiation (TBI) showed a better survival rate than those conditioned by polychemotherapy alone (p < 0.01), with an overall survival of 48% after 3 years for the former group as compared to 19% for the latter. Other parameters influencing survival were the number of graft CFU-GM, sex and age. A knowledge of these factors could provide a means of predicting the long term evolution of leukaemia following autologous bone marrow transplantation. However, the present results require validation by a prospective study taking into account recent therapeutic protocols with haematopoietic growth factors.