title: Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: impact of tyrosine kinase inhibitor and minimal residual disease.
abstract: The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P=0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P=0.057), but absence of pre-HCT TKI (HR 1.88; P=0.018), RIC (HR 1.891; P=0.054) and pre-HCT MRD(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA.
authors.forename: V
authors.identifier: 000000029325432X
authors.initials: V
authors.lastname: Bachanova
authors.affiliation: Bristol Adult BMT Unit, Bristol Children's Hospital, Bristol, UK.
authors.forename: D I
authors.initials: DI
authors.lastname: Marks
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Zhang
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: M
authors.initials: M
authors.lastname: de Lima
authors.affiliation: Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: M D
authors.initials: MD
authors.lastname: Aljurf
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Arellano
authors.affiliation: Department of Hematology and Oncology, University of Chicago Medicine, Chicago, IL, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Artz
authors.affiliation: Klinik und Poliklinik fur Stammzelltransplantation, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Bacher
authors.affiliation: Department of Hematology, University Hospital, Grenoble, France.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Cahn
authors.affiliation: Department of Bone Marrow Transplantation, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Y-B
authors.initials: YB
authors.lastname: Chen
authors.affiliation: Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Copelan
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Drobyski
authors.affiliation: Imperial College, Section of Hematology, Division of Experimental Medicine, Department of Medicine, London, UK.
authors.forename: R P
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Department of Hematology and Stem Cell Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Greer
authors.affiliation: Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Pediatric Hematology and Oncology, All Children's Hospital, St Petersburg, FL, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Hale
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kebriaei
authors.affiliation: Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Department of Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital/SA Pathology, Adelaide, South Australia, Australia.
authors.forename: I D
authors.initials: ID
authors.lastname: Lewis
authors.affiliation: Department of Hematology and Oncology, Alberta Children's Hospital, Calgary, Alberta, Canada.
authors.forename: V A
authors.initials: VA
authors.lastname: Lewis
authors.affiliation: Department of Hematology and Oncology, Strong Memorial Hospital, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Liesveld
authors.affiliation: Department of Hematology and Internal Medicine, Mayo Clinic Rochester, Rochester, MN, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Litzow
authors.affiliation: Department of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Loren
authors.affiliation: Department of Oncology, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Miller
authors.affiliation: Department of Hematology and Oncology, Shands HealthCare and University of Florida, Gainesville, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Norkin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: B
authors.initials: B
authors.lastname: Oran
authors.affiliation: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pidala
authors.affiliation: Department of Hematology, Rambam Medical Center, Haifa, Israel.
authors.forename: J M
authors.initials: JM
authors.lastname: Rowe
authors.affiliation: Department of Hematology and Stem Cell Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: B N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: W
authors.initials: W
authors.lastname: Saber
authors.affiliation: Department of Bone Marrow Transplantation and Leukemia, Barnes Jewish Hospital, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: R
authors.initials: R
authors.lastname: Vij
authors.affiliation: Bone Marrow and Stem Cell Transplant Center, Emory University Hospital, Atlanta, GA, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: Waller
authors.affiliation: Our Lady of Mercy Medical Center, Bronx, NY, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Wiernik
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Weisdorf
mesh_terms: D000328:Adult; D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000601:surgery*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012074:Remission Induction; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D011505:Protein-Tyrosine Kinases