BACKGROUND: The most frequent nonhematologic side effects associated with dasatinib therapy in patients with chronic myeloid leukemia (CML) are gastrointestinal, rash, and fluid retention syndromes. However, bleeding has been observed in some patients receiving dasatinib. In the current study, the authors investigated the risk factors and management of bleeding associated with dasatinib therapy for CML after imatinib failure. METHODS: The bleeding episodes associated with dasatinib therapy in 138 patients with CML who were consecutively treated at the study institution in clinical trials were evaluated. RESULTS: Bleeding occurred in 32 (23%) patients (grade >or=3 in 9 [7%] patients [according to National Cancer Institute Common Toxicity Criteria]), including in 12% of patients treated in chronic phase, 31% of patients treated in accelerated phase (AP), and 35% of patients treated in blast phase (BP) (P = .02). The majority of episodes (81%) affected the gastrointestinal tract. Basic coagulation studies were normal in 97% of patients who developed bleeding complications. Although 37% of episodes occurred with platelet counts >100 x 10(9)/L, multivariate analysis identified thrombocytopenia and advanced phase CML as risk factors for bleeding. A trend toward an increased risk with a twice-daily schedule was observed (P = .17). Management included dasatinib interruption for a median of 17 days (range, 3-51 days) in 47%, of patients and transfusions in 72% of patients. CONCLUSIONS: Bleeding occurs during dasatinib therapy, particularly in patients with AP or BP disease and low platelet counts. Appropriate clinical monitoring and the timely interruption of dasatinib therapy are warranted in this subset of patients. (c) 2009 American Cancer Society.
BACKGROUND: The most frequent nonhematologic side effects associated with dasatinib therapy in patients with chronic myeloid leukemia (CML) are gastrointestinal, rash, and fluid retention syndromes. However, bleeding has been observed in some patients receiving dasatinib. In the current study, the authors investigated the risk factors and management of bleeding associated with dasatinib therapy for CML after imatinib failure. METHODS: The bleeding episodes associated with dasatinib therapy in 138 patients with CML who were consecutively treated at the study institution in clinical trials were evaluated. RESULTS:Bleeding occurred in 32 (23%) patients (grade >or=3 in 9 [7%] patients [according to National Cancer Institute Common Toxicity Criteria]), including in 12% of patients treated in chronic phase, 31% of patients treated in accelerated phase (AP), and 35% of patients treated in blast phase (BP) (P = .02). The majority of episodes (81%) affected the gastrointestinal tract. Basic coagulation studies were normal in 97% of patients who developed bleeding complications. Although 37% of episodes occurred with platelet counts >100 x 10(9)/L, multivariate analysis identified thrombocytopenia and advanced phase CML as risk factors for bleeding. A trend toward an increased risk with a twice-daily schedule was observed (P = .17). Management included dasatinib interruption for a median of 17 days (range, 3-51 days) in 47%, of patients and transfusions in 72% of patients. CONCLUSIONS:Bleeding occurs during dasatinib therapy, particularly in patients with AP or BP disease and low platelet counts. Appropriate clinical monitoring and the timely interruption of dasatinib therapy are warranted in this subset of patients. (c) 2009 American Cancer Society.
Authors: Nicholas J Donato; Ji Y Wu; Jonathan Stapley; Hui Lin; Ralph Arlinghaus; Bharat B Aggarwal; Shishir Shishodia; Maher Albitar; Kimberly Hayes; Hagop Kantarjian; Moshe Talpaz; Shishir Shishodin Journal: Cancer Res Date: 2004-01-15 Impact factor: 12.701
Authors: Hagop Kantarjian; Charles Sawyers; Andreas Hochhaus; Francois Guilhot; Charles Schiffer; Carlo Gambacorti-Passerini; Dietger Niederwieser; Debra Resta; Renaud Capdeville; Ulrike Zoellner; Moshe Talpaz; Brian Druker; John Goldman; Stephen G O'Brien; Nigel Russell; Thomas Fischer; Oliver Ottmann; Pascale Cony-Makhoul; Thierry Facon; Richard Stone; Carole Miller; Martin Tallman; Randy Brown; Michael Schuster; Thomas Loughran; Alois Gratwohl; Franco Mandelli; Giuseppe Saglio; Mario Lazzarino; Domenico Russo; Michele Baccarani; Enrica Morra Journal: N Engl J Med Date: 2002-02-28 Impact factor: 91.245
Authors: Stephen G O'Brien; François Guilhot; Richard A Larson; Insa Gathmann; Michele Baccarani; Francisco Cervantes; Jan J Cornelissen; Thomas Fischer; Andreas Hochhaus; Timothy Hughes; Klaus Lechner; Johan L Nielsen; Philippe Rousselot; Josy Reiffers; Giuseppe Saglio; John Shepherd; Bengt Simonsson; Alois Gratwohl; John M Goldman; Hagop Kantarjian; Kerry Taylor; Gregor Verhoef; Ann E Bolton; Renaud Capdeville; Brian J Druker Journal: N Engl J Med Date: 2003-03-13 Impact factor: 91.245
Authors: Nicholas J Donato; Ji Yuan Wu; Jonathan Stapley; Gary Gallick; Hui Lin; Ralph Arlinghaus; Moshe Talpaz Journal: Blood Date: 2003-01-15 Impact factor: 22.113