title: Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.
abstract: BACKGROUND
  The long-term efficacy of a combination of chemotherapy and dasatinib in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is not well established.
  
  
  METHODS
  Patients received dasatinib with 8 cycles of alternating hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and high-dose cytarabine and methotrexate. Patients in complete remission (CR) continued maintenance dasatinib, vincristine, and prednisone for 2 years, which was followed by dasatinib indefinitely. Patients eligible for allogeneic stem cell transplantation (SCT) received it during their first CR.
  
  
  RESULTS
  Seventy-two patients with a median age of 55 years (range, 21-80 years) were treated; 69 (96%) achieved CR. Among them, 57 (83%) achieved cytogenetic CR after 1 cycle, and 64 (93%) achieved a major molecular response at a median of 4 weeks (range, 2-38 weeks). Sixty-five patients (94%) were negative for minimal residual disease assessed by flow cytometry at a median of 3 weeks (range, 2-37 weeks). Dasatinib-related grade 3 and 4 adverse events included bleeding, pleural/pericardial effusions, and elevated transaminases. With a median follow-up of 67 months (range, 33-97 months), 33 patients (46%) were alive, and 30 (43%) were in CR; 12 underwent allogeneic SCT. Thirty-nine patients died (3 at induction, 19 after relapse, 7 after SCT performed during first CR, and 10 during CR). The median disease-free survival and overall survival were 31 (range, 0.3-97 months) and 47 months (range, 0.2-97 months), respectively. Seven relapsed patients had BCR-ABL kinase domain mutations, including 4 with T315I.
  
  
  CONCLUSIONS
  A combination of chemotherapy with dasatinib is effective in achieving long-term remission for patients with newly diagnosed Ph + ALL.
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Farhad
authors: F
authors: Ravandi
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Susan M
authors: SM
authors: O'Brien
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Jorge E
authors: JE
authors: Cortes
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Deborah M
authors: DM
authors: Thomas
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Rebecca
authors: R
authors: Garris
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Stefan
authors: S
authors: Faderl
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Jan A
authors: JA
authors: Burger
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Michael E
authors: ME
authors: Rytting
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Alessandra
authors: A
authors: Ferrajoli
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: William G
authors: WG
authors: Wierda
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Srdan
authors: S
authors: Verstovsek
authors: Department of Cellular Therapy and Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Richard
authors: R
authors: Champlin
authors: Department of Cellular Therapy and Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Partow
authors: P
authors: Kebriaei
authors: Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Deborah A
authors: DA
authors: McCue
authors: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Xuelin
authors: X
authors: Huang
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Elias
authors: E
authors: Jabbour
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Guillermo
authors: G
authors: Garcia-Manero
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Zeev
authors: Z
authors: Estrov
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Hagop M
authors: HM
authors: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use; D000069439:Dasatinib / Q000008:administration & dosage* / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069439:Dasatinib; D008727:Methotrexate
keywords: Philadelphia chromosome; acute lymphoblastic leukemia; chemotherapy; combination; dasatinib