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The immunologic detection of minimal residual disease in acute leukemia
[published erratum appears in Blood 1990 Nov 1;76(7):1901]
D Campana, E Coustan-Smith and G Janossy
Department of Immunology, Royal Free Hospital School of Medicine, London,
UK.
Certain combinations of differentiation antigens are expressed on leukemia
blasts and are absent or extremely rare among normal progenitors in the
fetal liver and fetal and regenerating bone marrow. These combinations
include cCD3/TdT, a thymic feature retained on thymic-acute lymphoblastic
leukemia (T-ALL) blasts outside the thymus, and the coexpression of TdT and
myeloid markers (CD13, CD33) on a proportion of ALL and acute myeloid
leukemia (AML). Thus, double marker immunofluorescence assays are
operationally leukemia-specific and can be applied in 35% of acute
leukemias for detecting minimal disease at a less than 10(-4) level; only
rare cases, 2 of 35 in our study, switch these relevant features during
relapse. The sensitivity and specificity of these assays was tested as
follows. First, bone marrow samples taken from patients who had originally
presented with blasts expressing the leukemia-associated combinations but
were in full morphologic remission were studied, and varying numbers (less
than 0.01% to 10% of the mononuclear fraction) of cells with aberrant
features were identified in 11.6% of the cases. Second, the outcome of 19
patients with minimal disease identified immunologically while in complete
morphologic remission was investigated: all 19 patients have developed
systemic relapse within 4 to 25 (median 14.5) weeks. In contrast, 17 of 25
patients also morphologically in complete remission and without residual
disease identifiable immunologically after repeated testing are still in
morphologic and immunologic remission (follow-up 17 to 114 weeks, median 28
weeks). Only eight patients in this group have relapsed so far: in two
patients the relapse was localized in the cerebrospinal fluid, while in six
patients a systemic relapse was observed 6 to 51 (median 21.5) weeks after
the last negative immunologic bone marrow examination. In conclusion, no
false-positive results were detected with these sensitive assays, and the
introduction of appropriately planned prospective studies, including the
immunologic detection of residual leukemia, is justified on the basis of
these observations.
Volume 76,
Issue 1,
pp. 163-171,
07/01/1990
Copyright © 1990 by The American Society of Hematology
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