Autologous Bone Marrow Transplantation in High-Risk Remission B-Lineage Acute Lymphoblastic Leukemia Using a Cocktail of Three Monoclonal Antibodies (BA-l/CD24, BA-2/CD9, and BA-3/CD10) Plus Complement and 4-Hydroperoxycyclophosphamide for Ex Vivo Bone Marrow Purging

Fourteen patients with high-risk B-lineage acute lymphoblastic leukemia (ALL) in complete remission underwent autologous bone marrow transplantation (BMT) using a combined immunochemopurging protocol. A monoclonal antibody (MoAb) cocktail of BA-1, BA-2, and BA-3 plus rabbit complement (C‘) plus 4-hydroperoxycyclophosphamide (4-HC) was used t o eliminate residual occult leukemia cells from autografts. All patients were conditioned with single-dose total body irradiation (TBI) followed by high-dose Ara-C. All 14 patients engrafted at a median of 24 days (range, 12 to 36 days). Three patients are alive and disease free at 3.5 years, 3.9 years, and 4.1 years post-BMT. The Kaplan-Meier estimate and standard error of the probability of sustained remission was 23% 2 12% at 3.5 years post-BMT with a mean relapse-free interval of 1.4 +. 0.4 years. The diseasefree survival (DFS) at 3.5 years was 21 % f 11 %, with a mean DFS time of 1.3 f 0.4 years. A novel and quantitative minimal residual disease (MRD) detection assay, which combines fluorescence-activated multiparameter flow cytometry and cell sorting with leukemic progenitor cell (LPC) colony assays, was used to analyze remission BM samples from B-lineage ALL patients for residual LPC, and to evaluate the efficacy of ex vivo BM purging. Notably, the minimal residual leukemia burden before BMT, as measured by the percentage of B-lineage LPC in the pre-BMT remission BM samples,