title: Phase 2 study of intensified chemotherapy and allogeneic hematopoietic stem cell transplantation for older patients with acute lymphoblastic leukemia.
abstract: BACKGROUND
  Outcomes among older patients with acute lymphoblastic leukemia remain poor. This study sought to determine the efficacy of an intensified, multi-agent approach derived from a Dana-Farber consortium trial in younger adults for patients older than 50 years (trial identifier NCT00973752).
  
  
  METHODS
  The primary endpoint was overall survival (OS) at 1 year. Patients received induction chemotherapy with vincristine, prednisone, doxorubicin, and pegylated asparaginase. Imatinib was incorporated for Philadelphia chromosome-positive disease. After induction, the first consolidation incorporated clofarabine. Patients in remission could proceed to allogeneic hematopoietic cell transplantation (HCT) after induction and consolidation I. Those not receiving HCT went on to receive central nervous system, consolidation II, and continuation phases of treatment.
  
  
  RESULTS
  Thirty patients were enrolled: 19 achieved a complete remission (CR) after induction and 1 achieved CR after consolidation I for a CR rate of 67%. Sixteen patients underwent HCT. The proportion surviving at 1 year was 63%, and this met the primary endpoint. The 2-year OS rate was 52% (n = 30), and the 2-year disease-free survival rate was 52% for patients achieving CR (n = 20). There was no survival advantage among those undergoing HCT. Therapy-related hyperbilirubinemia prompted adjustments and limitations to asparaginase dosing.
  
  
  CONCLUSIONS
  Intensified chemotherapy can result in improved outcomes in comparison with historical data. Additional studies of similarly intensive regimens are warranted in this population. Cancer 2016;122:2379-2388. © 2016 American Cancer Society.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
authors.forename: Amir T
authors.initials: AT
authors.lastname: Fathi
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Stevenson
authors.affiliation: Monter Cancer Center, North Shore-Long Island Jewish Health System, Lake Success, New York.
authors.forename: Jonathan E
authors.identifier: http://orcid.org/0000-0003-2700-4784
authors.initials: JE
authors.lastname: Kolitz
authors.affiliation: Latter Day Saints Hospital, Salt Lake City, Utah.
authors.forename: Julie D
authors.initials: JD
authors.lastname: Asch
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Amrein
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
authors.forename: Eyal C
authors.initials: EC
authors.lastname: Attar
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: David P
authors.initials: DP
authors.lastname: Steensma
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
authors.forename: Julia
authors.initials: J
authors.lastname: Foster
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
authors.forename: Christine
authors.initials: C
authors.lastname: Connolly
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Ilene
authors.initials: I
authors.lastname: Galinsky
authors.affiliation: Monter Cancer Center, North Shore-Long Island Jewish Health System, Lake Success, New York.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Devoe
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Ballen
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D012074:Remission Induction; D016019:Survival Analysis; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers
keywords: Philadelphia chromosome; acute lymphoblastic leukemia; chemotherapy; older adults; stem cell transplant