Abstract |
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 to 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-Meiser estimate and standard error of the probability of sustained remission was 23% +/- 12% at 3.5 years post-BMT with a mean relapse-free interval of 1.4 +/- 0.4 years. The disease-free survival (DFS) at 3.5 years was 21% +/- 11%, with a mean DFS time of 1.3 +/- 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, indicated the outcome of the BMT. The median value for the minimal residual leukemia burden before BMT was 0.0035% (35 LPC/10(6) mononuclear cells). The Kaplan-Meier estimates and standard errors of the probability of remaining in remission after BMT were 43% +/- 19% for patients whose BM samples contained less than or equal to 0.0035% LPC and 0% +/- 0% for patients whose BM samples contained greater than 0.0035% B-lineage LPC (P less than .05). In contrast to the minimal residual leukemia burden measured by the described MRD assay system, the percentage of blasts or TdT+ cells in the remission BM samples did not correlate with the probability of relapse. The applied purging protocol showed variable success in destroying target B-lineage LPC populations contaminating the autografts. While in some cases purging was highly effective, eliminating up to greater than or equal to 4 logs of residual B-lineage LPC, in other cases only 0.1 to 0.2 logs of B-lineage LPC were purged.(ABSTRACT TRUNCATED AT 400 WORDS)
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Authors | F M Uckun, J H Kersey, R Haake, D Weisdorf, N K Ramsay |
Journal | Blood
(Blood)
Vol. 79
Issue 4
Pg. 1094-104
(Feb 15 1992)
ISSN: 0006-4971 [Print] United States |
PMID | 1531306
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antibodies, Monoclonal
- Antigens, CD
- Antigens, Differentiation
- Antigens, Neoplasm
- CD24 Antigen
- CD24 protein, human
- CD9 protein, human
- Membrane Glycoproteins
- Tetraspanin 29
- Cytarabine
- Cyclophosphamide
- Complement System Proteins
- Neprilysin
- perfosfamide
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Topics |
- Animals
- Antibodies, Monoclonal
- Antigens, CD
(immunology)
- Antigens, Differentiation
(immunology)
- Antigens, Neoplasm
(immunology)
- Bone Marrow
(pathology)
- Bone Marrow Purging
(methods)
- Bone Marrow Transplantation
- Burkitt Lymphoma
(pathology, therapy)
- CD24 Antigen
- Complement System Proteins
- Cyclophosphamide
(analogs & derivatives)
- Cytarabine
(therapeutic use)
- Flow Cytometry
- Fluorescent Antibody Technique
- Humans
- Membrane Glycoproteins
- Neoplasm Recurrence, Local
- Neprilysin
- Rabbits
- Remission Induction
- Tetraspanin 29
- Transplantation, Autologous
- Tumor Stem Cell Assay
- Whole-Body Irradiation
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