title: Secondary thrombotic microangiopathy in two patients with Philadelphia-positive hematological malignancies treated with imatinib mesylate.
abstract: Drug-mediated thrombotic microangiopathy may cause life-threatening medical emergencies. Novel targeted therapies have dramatically changed the prognosis of a number of oncological diseases. Tyrosine kinase inhibitors of the Breakpoint Cluster Region-Abelson (BCR-ABL) oncoprotein are used in patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Imatinib mesylate, which was the first anti-BCR-ABL tyrosine kinase inhibitor, has demonstrated a high tolerance profile and efficacy in these patients for many years. Good results have also been observed in patients with gastrointestinal stromal tumors. In this study, we describe two patients with Philadelphia chromosome-positive hematological malignancies who presented with secondary thrombotic microangiopathy that was most likely linked to the use of imatinib. Other potential causes of thrombotic microangiopathy were discarded, and the predisposing role of some comorbidities and potential short or long-term drug-drug interactions was assessed. The clinical and biological data were more indicative of atypical secondary hemolytic uremic syndrome in one of the cases and of secondary thrombotic microangiopathy with renal and cardiac impairment in the other, which is also categorized as secondary hemolytic uremic syndrome. The outcome was favorable after imatinib discontinuation and the treatment of severe cardiac and renal failures.
authors.affiliation: Department of Hematology and Cellular Therapy Unit, Hôpital Emile Muller, Mulhouse, France Centre de Competences on Thrombotic Microangiopathies, Region Alsace, France ojedam@ch-mulhouse.fr.
authors.forename: Mario
authors.initials: M
authors.lastname: Ojeda-Uribe
authors.affiliation: Laboratory of Hematology, Hôpital Emile Muller, Mulhouse, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Merieau
authors.affiliation: Laboratory of Hematology, Hôpital Emile Muller, Mulhouse, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Guillon
authors.affiliation: Central Pharmacy, Hôpital Emile Muller, Mulhouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Aujoulat
authors.affiliation: Centre de Competences on Thrombotic Microangiopathies, Region Alsace, France Department of Internal Medicine, Hôpital Emile Muller, Mulhouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hinschberger
authors.affiliation: Department of Hematology and Cellular Therapy Unit, Hôpital Emile Muller, Mulhouse, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Eisenmann
authors.affiliation: Department of Cardiology, Hôpital Emile Muller, Mulhouse, France.
authors.forename: David
authors.initials: D
authors.lastname: Kenizou
authors.affiliation: Centre de Competences on Thrombotic Microangiopathies, Region Alsace, France Laboratory of Hematology, Hôpital Emile Muller, Mulhouse, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Debliquis
authors.affiliation: Department of Biological Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Université Paris, Clamart, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
authors.affiliation: Centre de Competences on Thrombotic Microangiopathies, Region Alsace, France Department of Nephrology, Hôpital Emile Muller, Mulhouse, France.
authors.forename: François
authors.initials: F
authors.lastname: Chantrel
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000009:adverse effects*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy*; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D057049:Thrombotic Microangiopathies / Q000139:chemically induced* / Q000175:diagnosis
chemical_list: D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate
keywords: Chronic myeloid leukemia; Philadelphia chromosome-positive acute lymphoblastic leukemia; imatinib mesylate; secondary atypical hemolytic uremic syndrome; thrombotic microangiopathy