title: Reduced intensity conditioned allograft yields favorable survival for older adults with B-cell acute lymphoblastic leukemia.
abstract: Older adults with B-cell acute lymphoblastic leukemia (B-ALL) have poor survival. We examined the effectiveness of reduced intensity conditioning (RIC) hematopoietic cell transplant (HCT) in adults with B-ALL age 55 years and older and explored prognostic factors associated with long-term outcomes. Using CIBMTR registry data, we evaluated 273 patients (median age 61, range 55-72) with B-ALL with disease status in CR1 (71%), >CR2 (17%) and Primary Induction Failure (PIF)/Relapse (11%), who underwent RIC HCT between 2001 and 2012 using mostly unrelated donor (59%) or HLA-matched sibling (32%). Among patients with available cytogenetic data, the Philadelphia chromosome (Ph+) was present in 50%. The 3-year cumulative incidences of nonrelapse mortality (NRM) and relapse were 25% (95% confidence intervals (CI): 20-31%) and 47% (95% CI: 41-53%), respectively. Three-year overall survival (OS) was 38% (95% CI: 33-44%). Relapse remained the leading cause of death accounting for 49% of all deaths. In univariate analysis, 3 year risk of NRM was significantly higher with reduced Karnofsky performance status (KPS <90: 34% (95% CI: 25-43%) versus KPS ≥90 (18%; 95% CI: 12-24%, P = 0.006). Mortality was increased in older adults (66+ vs. 55-60: Relative Risk [RR] 1.51 95% CI: 1.00-2.29, P = 0.05) and those with advanced disease (RR 2.13; 95% CI: 1.36-3.34, P = 0.001). Survival of patients in CR1 yields 45% (95% CI: 38-52%) at 3 years and no relapse occurred after 2 years. We report promising OS and acceptable NRM using RIC HCT in older patients with B-ALL. Disease status in CR1 and good performance status are associated with improved outcomes. Am. J. Hematol. 92:42-49, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: James Cancer Center, Ohio State University, Columbus, OH.
authors.forename: Ashley
authors.initials: A
authors.lastname: Rosko
authors.affiliation: CIBMTR (Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH.
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.affiliation: Division of Medical Oncology, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Brenda
authors.initials: B
authors.lastname: Sandmaier
authors.affiliation: Emory University Hospital, Atlanta, GA.
authors.forename: H Jean
authors.initials: HJ
authors.lastname: Khoury
authors.affiliation: Section of Hematology/Oncology, University of Chicago School of Medicine, Chicago, IL.
authors.forename: Andrew
authors.initials: A
authors.lastname: Artz
authors.affiliation: M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Johnathan
authors.initials: J
authors.lastname: Brammer
authors.affiliation: The Ottawa Hospital Blood and Marrow Transplant Program and the Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bredeson
authors.affiliation: Indiana University Hospital/ Riley Hospital for Children, Indianapolis, IN.
authors.forename: Sherif
authors.initials: S
authors.lastname: Farag
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffit Cancer Center and Research Institute, Tampa, FL.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Kharfan-Dabaja
authors.affiliation: Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Adult Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, United Kingdom.
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.affiliation: Division of Clinical Hematology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: Rodrigo Martino
authors.initials: RM
authors.lastname: Bufarull
authors.affiliation: University of Kansas, Westwood, KS.
authors.forename: Joseph
authors.initials: J
authors.lastname: McGuirk
authors.affiliation: Hopital Saint-Antoine, APHP, Universite Pierre & Marie Curie, INSERM UMRs U938, Paris, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffit Cancer Center and Research Institute, Tampa, FL.
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.affiliation: St. Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Nivison-Smith
authors.affiliation: Barnes Jewish Hospital, St. Louis, MO.
authors.forename: Armin
authors.initials: A
authors.lastname: Rashidi
authors.affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Centre for Allogeneic Stem Cell Transplantation, Stockholm, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Ringden
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Seftel
authors.affiliation: Divsion of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weisdorf
authors.affiliation: Bone and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN.
authors.forename: Veronika
authors.initials: V
authors.lastname: Bachanova
authors.affiliation: CIBMTR (Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Wael
authors.initials: W
authors.lastname: Saber
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000628:therapy*; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods*