BACKGROUND: Systemic mastocytosis (SM) is a mast cell neoplasm in which neoplastic cells usually display the D816V-mutated variant of KIT. Cladribine (2CdA) and dasatinib are two drugs that counteract the in vitro growth of neoplastic mast cells in SM. However, only little is known about the in vivo effects of these drugs in SM. PATIENT AND METHODS: We report on a patient with highly aggressive interferon-alpha-resistant SM who was treated with 2CdA and dasatinib. In vitro pretesting revealed a response of neoplastic mast cells to both compounds with reasonable IC(50) values. RESULTS: The patient was treated with six cycles of 2CdA (0.13 mg kg(-1) intravenously daily on 5 consecutive days). Despite a short-lived major clinical response and a decrease in serum tryptase, the patient progressed to mast cell leukaemia after the sixth cycle of 2CdA. The patient then received two further courses of 2CdA followed by treatment with dasatinib (100 mg per os daily). However, no major response was obtained and the patient died from disease progression after 2 months. CONCLUSIONS: In a patient with rapidly progressing aggressive SM, neither 2CdA nor dasatinib produced a long-lasting response in vivo, despite encouraging in vitro results. For such patients, alternative treatment strategies have to be developed.
BACKGROUND: Systemic mastocytosis (SM) is a mast cell neoplasm in which neoplastic cells usually display the D816V-mutated variant of KIT. Cladribine (2CdA) and dasatinib are two drugs that counteract the in vitro growth of neoplastic mast cells in SM. However, only little is known about the in vivo effects of these drugs in SM. PATIENT AND METHODS: We report on a patient with highly aggressive interferon-alpha-resistant SM who was treated with 2CdA and dasatinib. In vitro pretesting revealed a response of neoplastic mast cells to both compounds with reasonable IC(50) values. RESULTS: The patient was treated with six cycles of 2CdA (0.13 mg kg(-1) intravenously daily on 5 consecutive days). Despite a short-lived major clinical response and a decrease in serum tryptase, the patient progressed to mast cell leukaemia after the sixth cycle of 2CdA. The patient then received two further courses of 2CdA followed by treatment with dasatinib (100 mg per os daily). However, no major response was obtained and the patient died from disease progression after 2 months. CONCLUSIONS: In a patient with rapidly progressing aggressive SM, neither 2CdA nor dasatinib produced a long-lasting response in vivo, despite encouraging in vitro results. For such patients, alternative treatment strategies have to be developed.
Authors: Celalettin Ustun; Andreas Reiter; Bart L Scott; Ryotaro Nakamura; Gandhi Damaj; Sebastian Kreil; Ryan Shanley; William J Hogan; Miguel-Angel Perales; Tsiporah Shore; Herrad Baurmann; Robert Stuart; Bernd Gruhn; Michael Doubek; Jack W Hsu; Eleni Tholouli; Tanja Gromke; Lucy A Godley; Livio Pagano; Andrew Gilman; Eva Maria Wagner; Tor Shwayder; Martin Bornhäuser; Esperanza B Papadopoulos; Alexandra Böhm; Gregory Vercellotti; Maria Teresa Van Lint; Christoph Schmid; Werner Rabitsch; Vinod Pullarkat; Faezeh Legrand; Ibrahim Yakoub-Agha; Wael Saber; John Barrett; Olivier Hermine; Hans Hagglund; Wolfgang R Sperr; Uday Popat; Edwin P Alyea; Steven Devine; H Joachim Deeg; Daniel Weisdorf; Cem Akin; Peter Valent Journal: J Clin Oncol Date: 2014-08-25 Impact factor: 44.544
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: Marta Lopes; Maria Dos Anjos Teixeira; Cláudia Casais; Vanessa Mesquita; Patrícia Seabra; Renata Cabral; José Palla-García; Catarina Lau; João Rodrigues; Maria Jara-Acevedo; Inês Freitas; Jose Ramón Vizcaíno; Jorge Coutinho; Luis Escribano; Alberto Orfao; Margarida Lima Journal: Case Rep Hematol Date: 2018-02-18