asta-z-7557 and Burkitt-Lymphoma

Burkitt's lymphoma has proved to be a very useful model for the evaluation of both massive therapy regimens and purging techniques. Results from several centres now confirm a number of general principles in relation to the use of ABMT procedures in this tumour. Patients in whom conventional chemotherapy has failed can be cured by massive therapy but this should be limited to those who have responded to salvage regimens or have only achieved first PR. Chemoresistant relapse is unlikely to be cured and the high probability of a transient response does not justify the procedure in such cases. Important ongoing clinical studies include the use of ABMT in first CR for CNS disease or B-cell ALL. Results in allogeneic grafts suggest that current massive therapy regimens are curative in only 20-50% of patients (Appelbaum and Thomas, 1983) and new combinations are, therefore, still required. Phase I and II studies in patients with 'resistant relapse' are investigating the use of sequential high-dose alkylating agents and role of TBI. It is of particular importance to develop effective conventional 'salvage' regimens. Recent experience indicates that the combination of high-dose cisplatin and VP 16 is useful; other possibilities include high-dose interferon and high-dose cytarabine. Purging techniques in BL are now at an advanced stage and the combination of immunological and chemical treatments, once of proven efficacy in individual patients at a laboratory level, should be the subject of randomized studies.

Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Burkitt Lymphoma; Cell Separation; Central Nervous System Diseases; Child; Combined Modality Therapy; Complement System Proteins; Cyclophosphamide; Humans; Magnetics; Recurrence; Transplantation, Autologous; Whole-Body Irradiation

We evaluated a novel ex vivo "purging" protocol for selective elimination of neoplastic T cells from human marrow by using a sensitive clonogenic assay. Immunotoxins (IT) were synthesized by conjugating ricin (R) to four different monoclonal antibodies (MoAb) directed against distinct markers of T cell lineage. Treatment with anti-p67-R produced effective elimination of leukemic T cells from human marrow. The cyclophosphamide congener mafosfamid (ASTA Z 7577) markedly enhanced the target cell cytotoxicity of IT and extended the final level of clonogenic kill 2 to 3 logs. Our data show that anti-p67-R in combination with mafosfamid resulted in a maximum elimination of 6.2 logs of neoplastic T cells with minimal toxicity to normal bone marrow progenitors. The efficiency of this protocol was not reduced in the presence of excess normal bone marrow cells. Similar findings were obtained by using a cocktail of four different anti-T cell IT. This approach is unique in combining both immunologic (IT) and chemical (mafosfamid) strategies for more effective ex vivo bone marrow purging in autologous bone marrow transplantation for T cell acute lymphoblastic leukemia/lymphoblastic lymphoma.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Burkitt Lymphoma; Cell Line; Cyclophosphamide; Growth Inhibitors; Humans; Leukemia, Lymphoid; Lymphocyte Depletion; Ricin; T-Lymphocytes; Tumor Stem Cell Assay

Topics: Animals; Bone Marrow; Bone Marrow Transplantation; Burkitt Lymphoma; Cell Line; Cell Separation; Cyclophosphamide; Hematopoietic Stem Cells; Humans; Leukemia; Leukemia, Experimental; Mice; Rats