title: Systemic mastocytosis (SM) associated with chronic eosinophilic leukemia (SM-CEL): detection of FIP1L1/PDGFRalpha, classification by WHO criteria, and response to therapy with imatinib.
abstract: Based on generally accepted criteria and the WHO-classification, a subset of patients with systemic mastocytosis (SM) have (or develop) an associated clonal hematologic non-mast cell lineage disease (SM-AHNMD). We describe a case of SM with coexisting chronic eosinophilic leukemia (SM-CEL). The patient, a 51-year-old male, was first seen in 1992 with small-sized infiltrates of spindle-shaped mast cells in his marrow, and marked eosinophilia. Retrospectively, a CHIC2 deletion and the FIP1L1/PDGFRalpha fusion gene-product were demonstrable by FISH analysis and RT-PCR, respectively. SM-associated organopathy or mediator-related symptoms were not recorded. However, the patient developed cardiomyopathy. Therapy with interferon-alpha, hydroxyurea, and corticosteroids were without effects. By contrast, therapy with imatinib was followed by a fast and sustained response with complete and stable regression of eosinophilia, drop in eosinophil cationic protein, and decrease of serum tryptase to normal levels. This case provides further evidence for the potential of co-existence of SM with a primary eosinophilic disorder (CEL) defined by the FIP1L1/PDGFRalpha fusion gene. Because of the availability of a superior targeted drug (imatinib), it is of importance to screen for FIP1L1/PDGFRalpha in suspected CEL with or without co-existing SM.
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Florian
authors.forename: Harald
authors.initials: H
authors.lastname: Esterbauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Binder
authors.forename: Leonhard
authors.initials: L
authors.lastname: Müllauer
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.forename: Christian
authors.initials: C
authors.lastname: Sillaber
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001549:Benzamides; D009202:Cardiomyopathies / Q000097:blood / Q000209:etiology; D047150:Eosinophil Cationic Protein / Q000097:blood; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D017681:Hypereosinophilic Syndrome / Q000097:blood / Q000145:classification / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000145:classification / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D034721:Mastocytosis, Systemic / Q000097:blood / Q000145:classification / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012074:Remission Induction; D012697:Serine Endopeptidases / Q000097:blood; D053802:Tryptases; D014944:World Health Organization; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics
chemical_list: D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; D047150:Eosinophil Cationic Protein; D012697:Serine Endopeptidases; D053802:Tryptases; D006918:Hydroxyurea