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Analysis of treatment failure in patients with minimally differentiated
acute myeloid leukemia (AML-M0)
R Stasi, G Del Poeta, A Venditti, M Masi, E Stipa, T Dentamaro, C Cox, B Dallapiccola and G Papa
Division of Hematology, University of Rome Tor Vergata, S. Eugenio
Hospital, Italy.
Reports of treatment of patients with minimally differentiated acute
myeloid leukemia (AML-M0) are limited, heterogeneous, and controversial. We
verified the prognosis of this subtype by analyzing the results of 189
consecutive patients with de novo AML. Fifteen cases fitting the criteria
of AML-M0 were identified. No clinical features distinguished them from
other patients with AML. The median age was 61 years (range 27 to 70), with
a leukocyte count ranging from 0.6 to 185 x 10(9)/L. In all cases the
leukemic cells expressed CD34 and reacted with at least one of the
antibodies to early myeloid antigens, ie, CD13, CD33, or myeloperoxidase.
Immunophenotypic analysis also showed positivity for CD7 in seven samples
and the multidrug-resistance P- glycoprotein (P-170) in six. Cytogenetic
analysis was abnormal in 12 of the 13 patients in whom an adequate number
of mitoses could be evaluated. No single abnormality prevailed, the most
common findings being trisomy 8 (three cases) and aberrations of chromosome
7 (two cases). Antileukemic treatment differed according to age, but for
remission induction, all patients received a combination of cytosine
arabinoside and an anthracycline or mitoxantrone. The prognosis of patients
with AML-M0 was remarkably poor as compared with the other
French-American-British subtypes. Whereas the overall rate of complete
remission (CR) was 58% with a median survival of 63 weeks, only 6 of the 15
patients with AML-M0 achieved a CR, and the median survival of this group
was 16 weeks (range 3 to 39). The major determinant of treatment failure
was unresponsiveness to chemotherapy, as only one patient died of infection
during the hypoplastic phase. The CR duration of responders was short,
ranging from 3 to 22 weeks, and no second remissions were observed. We
conclude that conventional combination chemotherapy yields disappointing
results in AML-M0. The reason for this may be the convergence of various
unfavorable prognostic factors, such as (1) the high incidence of
cytogenetic abnormalities; (2) the lack of differentiation features and the
expression of immaturity markers such as CD34 and CD7; and (3) the frequent
expression of P-170. Nonconventional therapeutic approaches should be
developed to alter the prognosis of this form of leukemia.
Volume 83,
Issue 6,
pp. 1619-1625,
03/15/1994
Copyright © 1994 by The American Society of Hematology
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