The objective of this section of the grant is to improve long term survival in high risk acute lymphoblastic leukemia (ALL) patients. This will be done utilizing allogeneic, autologous and unrelated donors for bone marrow transplantation. A biological stratification will occur whereby patients with matched siblings will receive allogeneic matched sibling marrow. For patients who lack donors, an unrelated donor transplant will be used if an unrelated donor is found within four months. Patients for whom an unrelated donor cannot be found will receive purged autologous bone marrow. Purging the marrow will be with B or T specificity immunotoxins and 4-hydroperoxycyclophosphamide. To decrease the post-transplant relapse rate, these patients will receive additional pre- and post-transplant therapy. Post-transplant immunostimulation using interleukin-2 (IL-2) will be evaluated in phase I and 11 studies in autologous B lineage leukemia patients. These trials will he extended to patients undergoing allogeneic or unrelated transplant as appropriate. In addition, a new pre-transplant conditioning therapy will be utilized employing immunotoxins. The safety, tolerance and efficacy of an anti-CD 19 monoclonal antibody linked to pokeweed antiviral protein will be evaluated (B43-PAP). Pilot studies will be performed in all B-lineage patients including those undergoing autologous, allogeneic and unrelated transplant in an effort to decrease their relapse rate. A secondary objective of this section of the grant is to evaluate the prognostic value of residual leukemic progenitor cells. The quality of remission will be determined in patients pre- and post-transplant to evaluate the impact of minimal residual disease using a quantitative assay system which combines multiparameter flow cytometry and cell sorting with leukemia progenitor cells (LPC assays). These evaluations will be performed in all patients pre-transplant and at day 28 and day 100 in an effort to evaluate the prognostic role of residual leukemia.
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