title: Sivelestat relieves respiratory distress refractory to dexamethasone in all-trans retinoic acid syndrome: a report of two cases.
abstract: Treatment with all-trans retinoic acid (ATRA) improves the prognosis of patients with acute promyelocytic leukemia (APL), but ATRA syndrome may occur as a possible fatal side effect, especially in cases refractory to medication or involving pulmonary hemorrhage. We describe two patients with APL who suffered from intracranial hemorrhage. The first patient was a 16-yr-old girl who was treated with ATRA and then developed respiratory distress refractory to treatment with dexamethasone combined with anthracycline-cytarabine cytoreduction therapy. Treatment with Sivelestat, a small molecule inhibitor of neutrophil elastase, achieved rapid improvement in oxygenation and chest radiograph findings, and the patient has been in complete remission for 24 months. The second patient was a 10-yr-old boy in whom pulmonary hemorrhage developed following administration of ATRA, dexamethasone and cytoreduction therapy. Aspiration and administration of Sivelestat improved oxygenation and he remained stable. Hematological improvement was also achieved, but the patient died of brain dysfunction because of cerebral edema accompanied by intracranial bleeding. The two cases suggest that Sivelestat may be effective as an additional agent in the treatment of refractory ATRA syndrome, and, therefore, prospective randomized studies of treatment protocols are warranted.
authors.affiliation: Department of Pediatrics2, Kawasaki Medical School, Kurashiki city, Okayama, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Hiroto
authors.initials: H
authors.lastname: Akaike
authors.forename: Ayaka
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Ouchi
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D019610:Cytoprotection; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000188:drug therapy; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy; D008297:Male; D011446:Prospective Studies; D011859:Radiography; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D018943:Anthracyclines; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D003561:Cytarabine; D014212:Tretinoin; D003907:Dexamethasone; C069195:sivelestat; D005998:Glycine