Successful Treatment of Relapse of Acute Promyelocytic Leukemia with a New Synthetic Retinoid, Am80

  1. Akihiro Takeshita, MD;
  2. Yukiko Shibata, MD;
  3. Kaori Shinjo, MD;
  4. Mitsuaki Yanagi, MD;
  5. Tadasu Tobita, MD;
  6. Kazunori Ohnishi, MD;
  7. Shuichi Miyawaki, MD;
  8. Koichi Shudo, PhD; and
  9. Ryuzo Ohno, MD

    All-trans retinoic acid (ATRA) has proven to be a major advance in the management of patients with acute promyelocytic leukemia. Several studies [1-5] have shown that a treatment program using ATRA for induction followed by several cycles of cytotoxic chemotherapy for consolidation yields overall survival rates superior to those produced by chemotherapy alone. Nonetheless, ATRA has several important limitations, one of which is the rapid development of resistance to it by patients [6]. We report here, for the first time, that the new synthetic retinoid Am80 (4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid) (Figure 1) [7, 8] induced complete remission without serious adverse effects in the only two patients whom we have treated with this drug for relapse from ATRA-induced complete remission of acute promyelocytic leukemia.

    Figure 1. Molecular structures of Am80 and all-trans retinoic acid.

    Case Reports

    Patient 1

    A 44-year-old man presented in February 1993 with generalized bleeding tendency and leukocytosis (95% of leukocytes were promyelocytes). A bone marrow smear showed hypercellular marrow in which 96% of the leukocytes were promyelocytes. Chromosome analysis showed t(15; 17)(q22; q21), and acute promyelocytic leukemia was diagnosed. Treatment with ATRA at a daily dose of 45 mg/m2 body surface area was administered. Complete remission was attained on 18 May 1993. The patient then received three courses of consolidation and six courses of maintenance chemotherapy ending in March 1994, according to the AML92 protocol of the Japan Adult Leukemia Study Group [4].

    The patient again presented with severe bleeding tendency in March 1995. A bone marrow smear showed hypercellular marrow in which 90% of the leukocytes were promyelocytes containing Auer bodies. …

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    1. Ann Intern Med May 15, 1996 vol. 124 no. 10 893-896
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