BACKGROUND: Mastocytosis is characterized by the abnormal proliferation of mast cells in 1 or more organs. In most patients, a mutation is present in the gene for C-KIT, resulting in deregulation of the c-kit receptor. Imatinib mesylate is a potent inhibitor of c-kit receptor tyrosine kinase activity. Therefore, the authors evaluated the efficacy and safety of imatinib mesylate as treatment for patients with systemic mastocytosis. METHODS: Patients with systemic mastocytosis received imatinib mesylate orally at a dose of 400 mg once daily for 3 to 6 months. Low doses of prednisone were added during the first 2 weeks. Endpoints were reductions in serum tryptase, urinary N-methylhistamine excretion, skin lesions, the number of mast cells in bone marrow sections, hepatomegaly and/or splenomegaly, and symptoms. RESULTS: Of 14 patients who were included in the study, 11 patients had the D816V mutation. One patient expressed the FIP1L1-PDGFR-alpha rearrangement gene. In 2 patients, no mutation was found. In 10 patients, serum tryptase levels decreased >20%. In all patients, urinary N-methylhistamine excretion was reduced. In 8 of 13 evaluable patients, the number of mast cells in the bone marrow decreased. Skin symptoms diminished in 5 of 9 patients. Hepatosplenomegaly improved in 3 of 6 patients. Symptoms decreased in 8 of 13 patients. In all patients who had the D816V mutation, reductions in > or =2 endpoints were achieved. In the patient who expressed the FIP1L1-PDGFR-alpha rearrangement gene, a complete response was attained. In general, imatinib mesylate was tolerated well. CONCLUSIONS: Imatinib mesylate was effective in patients with systemic mastocytosis, including those who had the D816V mutation.
BACKGROUND: Mastocytosis is characterized by the abnormal proliferation of mast cells in 1 or more organs. In most patients, a mutation is present in the gene for C-KIT, resulting in deregulation of the c-kit receptor. Imatinib mesylate is a potent inhibitor of c-kit receptor tyrosine kinase activity. Therefore, the authors evaluated the efficacy and safety of imatinib mesylate as treatment for patients with systemic mastocytosis. METHODS:Patients with systemic mastocytosis received imatinib mesylate orally at a dose of 400 mg once daily for 3 to 6 months. Low doses of prednisone were added during the first 2 weeks. Endpoints were reductions in serum tryptase, urinary N-methylhistamine excretion, skin lesions, the number of mast cells in bone marrow sections, hepatomegaly and/or splenomegaly, and symptoms. RESULTS: Of 14 patients who were included in the study, 11 patients had the D816V mutation. One patient expressed the FIP1L1-PDGFR-alpha rearrangement gene. In 2 patients, no mutation was found. In 10 patients, serum tryptase levels decreased >20%. In all patients, urinary N-methylhistamine excretion was reduced. In 8 of 13 evaluable patients, the number of mast cells in the bone marrow decreased. Skin symptoms diminished in 5 of 9 patients. Hepatosplenomegaly improved in 3 of 6 patients. Symptoms decreased in 8 of 13 patients. In all patients who had the D816V mutation, reductions in > or =2 endpoints were achieved. In the patient who expressed the FIP1L1-PDGFR-alpha rearrangement gene, a complete response was attained. In general, imatinib mesylate was tolerated well. CONCLUSIONS:Imatinib mesylate was effective in patients with systemic mastocytosis, including those who had the D816V mutation.
Authors: Tzu-Yin Lin; Joelle Fenger; Sridhar Murahari; Misty D Bear; Samuel K Kulp; Dasheng Wang; Ching-Shih Chen; William C Kisseberth; Cheryl A London Journal: Blood Date: 2010-03-16 Impact factor: 22.113
Authors: Christopher L Corless; Patina Harrell; Mario Lacouture; Troy Bainbridge; Claudia Le; Ken Gatter; Clifton White; Scott Granter; Michael C Heinrich Journal: J Mol Diagn Date: 2006-11 Impact factor: 5.568
Authors: Jason Gotlib; Animesh Pardanani; Cem Akin; Andreas Reiter; Tracy George; Olivier Hermine; Hanneke Kluin-Nelemans; Karin Hartmann; Wolfgang R Sperr; Knut Brockow; Lawrence B Schwartz; Alberto Orfao; Daniel J Deangelo; Michel Arock; Karl Sotlar; Hans-Peter Horny; Dean D Metcalfe; Luis Escribano; Srdan Verstovsek; Ayalew Tefferi; Peter Valent Journal: Blood Date: 2013-01-16 Impact factor: 22.113
Authors: Sita Virakul; Leendert van Steensel; Virgil A S H Dalm; Dion Paridaens; P Martin van Hagen; Willem A Dik Journal: Eur Thyroid J Date: 2014-12-06