Acute Promyelocytic Leukemia Complicated by Massive Intracerebral Hemorrhage: Safety and Efficacy of Replacing Conventional Chemotherapy with Arsenic Trioxide in an Adolescent

Introduction

Acute promyelocytic leukemia (APL) comprises ~7% of pediatric acute myeloblastic leukemia and is characterized by leukemic promyelocytes in the peripheral blood smear, a chromosomal translocation involving the RARa gene, and coagulopathy (Hillestad LK. Acta Med Scand 1957; 159: 189–194; Look AT. Science 1997; 278: 1059–1064). Early mortality is mostly attributable to severe, frequently intracerebral bleeding. Therapy guidelines in the pediatric setting rely on international treatment optimization protocols, such as those introduced by the Berlin-Frankfurt-Münster (BFM) and Italian Pediatric Hematology and Oncology Group (AIEOP) (Creutzig U et al. Br J Haematol 2010; 149: 399–409; Testi AM et al. Blood 2005; 106: 447–453). Response rates have improved tremendously upon introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which can induce apoptosis in APL cells. In 2009, the European LeukemiaNet recommended ATRA combined with anthracycline-based chemotherapy for induction therapy whereas ATO-based regimens were the first option for treatment of relapsed APL (Sanz MA et al. Blood 2009; 113: 1875–1891).

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^* Contributed equally.