Autologous bone marrow transplantation with marrow decontaminated by immunotoxin T 101 in the treatment of leukemia and lymphoma: first clinical observations.
Four patients with T-cell malignancies of poor prognosis (three with non-Hodgkin's lymphoma and one with acute lymphoblastic leukemia) received the following consolidation therapy for complete or partial remission: cyclophosphamide (120 mg/kg) plus total-body irradiation, followed by reinfusion of cryopreserved autologous marrow previously purged in vitro by immunotoxin T 101 (SR 41322). This immunotoxin is made of the murine monoclonal T 101 antibody coupled to chain A of ricin. The doses of immunotoxin used were 10(-9) and 10(-8) M, and the durations of incubation were 4 and 20 hours at 37 degrees C. Recovery of progenitors CFUc and BFUe was total following incubation with immunotoxin T 101, but diminished after cryopreservation (15%-80% for CFUc, 33%-47% for BFUe), suggesting an increased fragility of the incubated progenitors to freezing. In every case, hematopoietic recovery occurred within normal time periods, with a wbc count greater than 10(9)/L and a platelet count greater than 50 X 10(9)/L on Day 22 (range, 15-31) and Day 21 (range, 22-47), respectively, demonstrating the feasibility of autologous bone marrow transplantation with marrow pretreated by immunotoxin. However, the slow recovery of lymphocytes and the development of severe infections in two patients may indicate that an in-depth study of immunological reconstitution after in vitro treatment of the marrow with immunotoxin T 101 is necessary.
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000276:immunology*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic; D004341:Drug Evaluation; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007945:Leukemia, Lymphoid / Q000097:blood / Q000401:mortality / Q000628:therapy*; D008223:Lymphoma / Q000097:blood / Q000401:mortality / Q000628:therapy*; D008297:Male; D008479:Mediastinal Neoplasms / Q000628:therapy; D011379:Prognosis; D012276:Ricin / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D013048:Specimen Handling; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D003561:Cytarabine; D003520:Cyclophosphamide; D012276:Ricin