Systemic mastocytosis (SM) associated with chronic eosinophilic leukemia (SM-CEL): detection of FIP1L1/PDGFRalpha, classification by WHO criteria, and response to therapy with imatinib

Leuk Res. 2006 Sep;30(9):1201-5. doi: 10.1016/j.leukres.2005.11.014. Epub 2006 Jan 6.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Benzamides
  • Cardiomyopathies / blood
  • Cardiomyopathies / etiology
  • Eosinophil Cationic Protein / blood
  • Humans
  • Hydroxyurea / administration & dosage
  • Hypereosinophilic Syndrome / blood
  • Hypereosinophilic Syndrome / classification
  • Hypereosinophilic Syndrome / complications
  • Hypereosinophilic Syndrome / drug therapy*
  • Hypereosinophilic Syndrome / genetics
  • Imatinib Mesylate
  • Interferon-alpha / administration & dosage
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / classification
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Male
  • Mastocytosis, Systemic / blood
  • Mastocytosis, Systemic / classification
  • Mastocytosis, Systemic / complications
  • Mastocytosis, Systemic / drug therapy*
  • Mastocytosis, Systemic / genetics
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics
  • Piperazines / administration & dosage*
  • Pyrimidines / administration & dosage*
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Remission Induction
  • Serine Endopeptidases / blood
  • Tryptases
  • World Health Organization
  • mRNA Cleavage and Polyadenylation Factors / genetics

Substances

  • Adrenal Cortex Hormones
  • Antineoplastic Agents
  • Benzamides
  • Interferon-alpha
  • Oncogene Proteins, Fusion
  • Piperazines
  • Pyrimidines
  • mRNA Cleavage and Polyadenylation Factors
  • Imatinib Mesylate
  • FIP1L1-PDGFRA fusion protein, human
  • Receptor, Platelet-Derived Growth Factor alpha
  • Eosinophil Cationic Protein
  • Serine Endopeptidases
  • Tryptases
  • Hydroxyurea