title: The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen.
abstract: The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.
authors.affiliation: Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, and Institute of Research Josep Carreras, Barcelona, Spain. Electronic address: aurbano@clinic.ub.es.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Pavletic
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Flowers
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: John P
authors.initials: JP
authors.lastname: Klein
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Mei-Jie
authors.initials: MJ
authors.lastname: Zhang
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Carreras
authors.affiliation: Department of Haemato-oncology, St. Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom.
authors.forename: Silvia
authors.initials: S
authors.lastname: Montoto
authors.affiliation: Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.affiliation: Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh, Saudi Arabia.
authors.forename: Mahmoud D
authors.initials: MD
authors.lastname: Aljurf
authors.affiliation: Section of Hematology Oncology, Banner MD Anderson Cancer Center, Gilbert, Arizona.
authors.forename: Görgün
authors.initials: G
authors.lastname: Akpek
authors.affiliation: The Ottawa Hospital Blood and Marrow Transplant Program and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Bredeson
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Luciano J
authors.initials: LJ
authors.lastname: Costa
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dandoy
authors.affiliation: South Texas Veterans Health Care System and University of Texas Health Science Center San Antonio, San Antonio, Texas.
authors.forename: César O
authors.initials: CO
authors.lastname: Freytes
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Temple Health, Philadelphia, Pennsylvania.
authors.forename: Henry C
authors.initials: HC
authors.lastname: Fung
authors.affiliation: Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hayashi
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: David J
authors.initials: DJ
authors.lastname: Inwards
authors.affiliation: Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Divison of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.affiliation: Divison of Hematology/Oncology, Department of Internal Medicine, Louisiana State University Health, Shreveport, Louisiana.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Munker
authors.affiliation: Department of Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Olsson
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.affiliation: Department of Medicine, Abramson Cancer Center, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.
authors.forename: Ran
authors.initials: R
authors.lastname: Reshef
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Ayman
authors.initials: A
authors.lastname: Saad
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Department of Hematology, Academische Ziekenhuis, Maastricht, Netherlands.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Schouten
authors.affiliation: Section of Hematology/Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: Department of Hematology, Hôpital Saint Louis, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Department of Internal Medicine, Stony Brook University Medical Center, Stony Brook, New York.
authors.forename: Baldeep
authors.initials: B
authors.lastname: Wirk
authors.affiliation: Division of Hematology/Oncology, Center for Cancer and Blood Disorders, Children's Hospital/Louisiana State University Medical Center, New Orleans, Louisiana.
authors.forename: Lolie C
authors.initials: LC
authors.lastname: Yu
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Wael
authors.initials: W
authors.lastname: Saber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000150:complications*; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008223:Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012008:Recurrence; D000069283:Rituximab / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000069283:Rituximab
keywords: Graft-versus-host disease; Lymphoma