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Autologous bone marrow transplantation in high-risk remission B-lineage
acute lymphoblastic leukemia using a cocktail of three monoclonal
antibodies (BA-1/CD24, BA-2/CD9, and BA-3/CD10) plus complement and 4-
hydroperoxycyclophosphamide for ex vivo bone marrow purging
FM Uckun, JH Kersey, R Haake, D Weisdorf and NK Ramsay
Bone Marrow Transplantation Program, University of Minnesota Health
Sciences Center, Minneapolis 55455.
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)
Volume 79,
Issue 4,
pp. 1094-1104,
02/15/1992
Copyright © 1992 by The American Society of Hematology
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