title: A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation.
abstract: OBJECTIVE
  Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life.
  
  
  METHODS
  We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m(2) i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy.
  
  
  RESULTS
  SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%-43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%-44%) randomized to rituximab. Six (17%; 95% CI, 7%-34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%-29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27(+)) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients.
  
  
  CONCLUSIONS
  These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab.
authors.affiliation: Department of Medicine/Division of Blood and Marrow Transplant, Stanford University School of Medicine, Stanford, California.
authors.forename: Sally
authors.initials: S
authors.lastname: Arai
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.affiliation: Division of Oncology, Section of Bone Marrow Transplantation, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Iskra
authors.initials: I
authors.lastname: Pusic
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chai
authors.affiliation: Division of Hematology, Internal Medicine, Ohio State University, Columbus, Ohio.
authors.forename: Samantha
authors.initials: S
authors.lastname: Jaglowski
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Nandita
authors.initials: N
authors.lastname: Khera
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Palmer
authors.affiliation: Department of Medicine/Division of Blood and Marrow Transplant, Stanford University School of Medicine, Stanford, California.
authors.forename: George L
authors.initials: GL
authors.lastname: Chen
authors.affiliation: Department of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Madan H
authors.initials: MH
authors.lastname: Jagasia
authors.affiliation: Mayer Weill Cornell Medical College, New York, New York.
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Mayer
authors.affiliation: Department of Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: William A
authors.initials: WA
authors.lastname: Wood
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Hyun
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.affiliation: Department of Medicine/Division of Blood and Marrow Transplant, Stanford University School of Medicine, Stanford, California.
authors.forename: David B
authors.initials: DB
authors.lastname: Miklos
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Howard M
authors.initials: HM
authors.lastname: Shulman
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sarantopoulos
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. mflowers@fhcrc.org.
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects; D018592:Cross-Over Studies; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069283:Rituximab / Q000627:therapeutic use*; D012598:Sclerosis / Q000188:drug therapy*; D012871:Skin Diseases / Q000188:drug therapy*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D055815:Young Adult
chemical_list: D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000069283:Rituximab; D000068877:Imatinib Mesylate