title: Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning.
abstract: OBJECTIVE
  The clinical safety and efficacy of intravenous busulfan and fludarabine (IV Bu/Flu) myeloablative conditioning as well as graft-versus-host disease (GVHD) prophylaxis with high-dose, post-transplantation cyclophosphamide (PTCy) have been demonstrated independently in several single-institutional studies. We hypothesized that combining these two promising approaches in a multi-institutional study of human leukocyte antigen (HLA) -matched bone marrow transplantation would provide low rates of severe acute and chronic GVHD, low toxicity, and effective disease control.
  
  
  METHODS
  Ninety-two adult patients (median age, 49 years; range, 21 to 65 years) with high-risk hematologic malignancies were enrolled at three centers (clinical trial No. NCT00809276). Forty-five patients received related allografts, and 47 received unrelated allografts. GVHD prophylaxis was solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4.
  
  
  RESULTS
  The cumulative incidences of grades 2 to 4 acute, grades 3 to 4 acute, and chronic GVHD were 51%, 15%, and 14%, respectively. Nonrelapse mortality (NRM) at 100 days and 1 year were 9% and 16%, respectively. With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P = .0005; OS, P = .019).
  
  
  CONCLUSIONS
  This multi-institutional study demonstrates that PTCy can be safely and effectively combined with IV Bu/Flu myeloablative conditioning and confirms PTCy's efficacy as single-agent, short-course GVHD prophylaxis for both acute and chronic GVHD after bone marrow transplantation from HLA-matched donors.
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kanakry
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Donnell
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Terry
authors.initials: T
authors.lastname: Furlong
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: de Lima
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Marta
authors.initials: M
authors.lastname: Medeot
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Marco
authors.initials: M
authors.lastname: Mielcarek
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jones
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Thall
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Borje S
authors.initials: BS
authors.lastname: Andersson
authors.affiliation: Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. luznile@jhmi.edu.
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
mesh_terms: D000328:Adult; D000368:Aged; D001499:Bayes Theorem; D002066:Busulfan / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine