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All-trans retinoic acid as a differentiation therapy for acute
promyelocytic leukemia. I. Clinical results [see comments]
S Castaigne, C Chomienne, MT Daniel, P Ballerini, R Berger, P Fenaux and L Degos
Departement d'Hematologie, Hopital St Louis, Paris, France.
Twenty-two patients with acute promyelocytic leukemia were treated with
all-trans retinoic acid (RA, 45 mg/m2 per day) for 90 days. Of the 22, four
patients were previously untreated, two were resistant after conventional
chemotherapy, and 16 were in first (n = 11), second (n = 4), or third (n =
1) relapse. We observed 14 complete response, four transient responses, one
failure, and three early deaths. Length of hospitalization and number of
transfusions were notably reduced in complete responders. Correction of
coagulation disorders and an increase of WBCs were the first signs of
all-trans RA efficacy. Morphologic analysis performed at days 0, 15, 30,
45, 60, and 90 showed that complete remissions were obtained without bone
marrow (BM) hypoplasia. Presence of Auer rods in the maturing cells
confirmed the differentiation effect of the treatment. At remission, the
t(15;17) initially present in 20 patients was not found. The in vitro
studies showed a differentiation in the presence of all-trans RA in 16 of
the 18 tested cases. The single nonresponder to all trans RA in vitro did
not respond in vivo. Adverse effects of RA therapy--skin and mucosa
dryness, hypertriglyceridemia, and increase of hepatic transaminases-- were
frequently noted. We also observed bone pain in 11 patients and
hyperleukocytosis in four patients. Whether maintenance treatment consisted
of low-dose chemotherapy or all-trans RA, early relapses were observed.
Five patients are still in complete remission (CR) at 4 to 13 months. Our
study confirms the major efficacy of all-trans RA in M3, even in relapsing
patients. Remissions are obtained by a differentiation process.
Volume 76,
Issue 9,
pp. 1704-1709,
11/01/1990
Copyright © 1990 by The American Society of Hematology
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