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Retinoic acid treatment of acute promyelocytic leukemia: in vitro and in
vivo observations
PJ Flynn, WJ Miller, DJ Weisdorf, DC Arthur, R Brunning and RF Branda
We describe in vitro studies and a therapeutic trial of retinoic acid (RA)
in a patient with acute promyelocytic leukemia (APL) refractory to
chemotherapy. Bone marrow promyelocytes from the patient, prior to RA,
matured morphologically in liquid culture with RA (97% maturing myeloid
cells compared with 26% in control cultures at 7 days). RA-cultured cells
displayed leukocyte alkaline phosphatase activity and cytoplasmic
maturation (by electron microscopy). Retinoic-acid-treated cells, compared
to controls, demonstrated increased functional maturation, with
phagocytosis of opsonized zymosan (90% versus 10%) and production of
superoxide (measured by nitroblue tetrazolium reduction) in response to
phorbol ester, opsonized zymosan, or the chemotaxin F-met-leu-phe. There
was no evidence of active proliferation in the cultures. RA- treated cells
continued to show 15;17 chromosomal translocation after 7 days in culture.
The patient was treated with oral 13-cis-retinoic acid (100 mg/sq m/day)
for 13 days. During that time, the peripheral white blood count rose from
300 cu mm to 6,700 cu mm, and the maturing myeloid cell count rose from 54
cu mm to 3,800 cu mm. Bone marrow maturing cells increased from 1.8% to
8.0%. Despite the increasing number of maturing myeloid cells, the patient
died on day 13 from disseminated candidiasis. These data confirm that RA
induces maturation of leukemic promyelocytes in vitro and suggest that
similar maturation is achievable in vivo. We suggest that oral retinoic
acid may be a useful adjunct in the treatment of APL.
Volume 62,
Issue 6,
pp. 1211-1217,
12/01/1983
Copyright © 1983 by The American Society of Hematology
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