Transplantation of monoclonal antibody-purged autologous bone marrow for treatment of poor risk common acute lymphoblastic leukemia.
Two murine monoclonal antibodies, FMC-8 and WM-21, reactive with the human leucocyte differentiation antigens CD-9 (p-24) and CD-10 (CALLA), respectively, have been used for purging leukemic cells from remission bone marrow. Nine patients with the common variant of acute lymphoblastic leukemia (c-ALL) in second or subsequent remission underwent bone marrow harvesting. Bone marrow mononuclear cells underwent lytic incubation in vitro with antibodies FMC-8 and WM-21, and rabbit serum as a source of complement, and were then cryopreserved. A mean of 0.90 +/- 0.50 x 10(8) nucleated cells per kilogram of recipient body weight remained after treatment, with 0.38 +/- 0.24 x 10(8) nucleated cells and 8.3 +/- 10.3 x 10(4) CFUGM per kg being recovered on thawing. Seven patients subsequently received marrow-ablative treatment with high dose cyclophosphamide (120 mg/kg) and fractionated total body irradiation (12 Gy), followed by infusion of antibody-purged autologous bone marrow. Three deaths due to sepsis occurred within the first 35 days, compounded in one patient by poor marrow engraftment. All other patients engrafted promptly, and four remain in continuous complete remission at 2, 6, 9, and 28 months after transplantation. The procedure carries a substantial risk of early toxicity, but offers a significant chance of prolonged unmaintained remission to selected patients with poor prognosis acute lymphoblastic leukemia.
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D015260:Neprilysin; D012307:Risk Factors; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D003520:Cyclophosphamide; D015260:Neprilysin