title: Results of a 2-arm, phase 2 clinical trial using post-transplantation cyclophosphamide for the prevention of graft-versus-host disease in haploidentical donor and mismatched unrelated donor hematopoietic stem cell transplantation.
abstract: BACKGROUND
  High-dose, post-transplantation cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD) has improved outcomes in haploidentical (HAPLO) stem cell transplantation (SCT). However, it remains unclear whether this strategy is effective in SCT from 1-antigen human leukocyte antigen (HLA)-mismatched unrelated donors (9/10 MUD) and how the outcomes of these patients compare with those of haploidentical transplantation recipients.
  
  
  METHODS
  A parallel, 2-arm, nonrandomized phase 2 clinical trial was conducted of melphalan-based reduced-intensity conditioning with PTCy, tacrolimus, and mycophenolate mofetil to prevent GVHD in patients with high-risk hematologic malignancies who underwent HAPLO (n = 60) or 9/10 MUD (n = 46) SCT.
  
  
  RESULTS
  The 1-year overall and progression-free survival rates were 70% and 60%, respectively, in the HAPLO arm and 60% and 47%, respectively, in the 9/10 MUD arm. The day +100 cumulative incidence of grade II to IV acute GVHD and grade III to IV acute GVHD was 28% and 3%, respectively, in the HAPLO arm and 33% and 13%, respectively, in the 9/10 MUD arm. The 2-year cumulative incidence of chronic GVHD was 24% in the HAPLO arm and 19% in the 9/10 MUD arm. The 1-year cumulative incidence of nonrelapse mortality was 21% in the HAPLO arm and 31% in the 9/10 MUD arm, and the 1-year relapse rate was 19% in the HAPLO arm and 25% in the 9/10 MUD arm.
  
  
  CONCLUSIONS
  Although this was a nonrandomized study and could not serve as a direct comparison between the 2 groups, the authors conclude that PTCy-based GVHD prophylaxis is effective for both HAPLO and 9/10 MUD SCTs. Prospective randomized trials will be required to compare the efficacies of alternative donor options for patients lacking HLA-matched donors. Cancer 2016;122:3316-3326. © 2016 American Cancer Society.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.lastname: Gaballa
authors.affiliation: University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Isabell
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authors.lastname: Ge
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Riad
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authors.lastname: El Fakih
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Brammer
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.lastname: Kongtim
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.lastname: Cao
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.lastname: Rondon
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Julianne
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authors.lastname: Chen
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.lastname: Lombardi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.lastname: Korbling
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Betul
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authors.lastname: Oran
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.lastname: Ahmed
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nina
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authors.lastname: Shah
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Katayoun
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authors.lastname: Rezvani
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.lastname: Alousi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.lastname: Nieto
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.lastname: Popat
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Issa
authors.initials: I
authors.lastname: Khouri
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. sciurea@mdanderson.org.
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mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: 9/10 matched unrelated donors; graft-versus-host disease; haploidentical transplantation; hematologic malignancies; post-transplantation cyclophosphamide