title: Clinical Practice Recommendations for Use of Allogeneic Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia on Behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation.
abstract: We sought to establish clinical practice recommendations to redefine the role of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with chronic lymphocytic leukemia (CLL) in an era of highly active targeted therapies. We performed a systematic review to identify prospective randomized controlled trials comparing allo-HCT against novel therapies for treatment of CLL at various disease stages. In the absence of such data, we invited physicians with expertise in allo-HCT and/or CLL to participate in developing these recommendations. We followed the Grading of Recommendations Assessment, Development and Evaluation methodology. For standard-risk CLL we recommend allo-HCT in the absence of response or if there is evidence of disease progression after B cell receptor (BCR) inhibitors. For high-risk CLL an allo-HCT is recommended after failing 2 lines of therapy and showing an objective response to BCR inhibitors or to a clinical trial. It is also recommended for patients who fail to show an objective response or progress after BCR inhibitors and receive BCL-2 inhibitors, regardless of whether an objective response is achieved. For Richter transformation, we recommend allo-HCT upon demonstration of an objective response to anthracycline-based chemotherapy. A reduced-intensity conditioning regimen is recommended whenever indicated. These recommendations highlight the rapidly changing treatment landscape of CLL. Newer therapies have disrupted prior paradigms, and allo-HCT is now relegated to later stages of relapsed or refractory CLL.
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Florida; Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, Florida. Electronic address: Mohamed.Kharfan-Dabaja@Moffitt.org.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.affiliation: Program for Comparative Effectiveness Research, University of South Florida College of Medicine, Tampa, Florida.
authors.forename: Ambuj
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.affiliation: Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: Department of Onco-Haematology and Division of Experimental Oncology, IRCCS San Raffaele Hospital and Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Florida; Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, Florida.
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.affiliation: Department of Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dreger
authors.affiliation: Department of Hematology, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
authors.affiliation: Adult 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: Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Farrukh T
authors.initials: FT
authors.lastname: Awan
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Florida; Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, Florida.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Ayala
authors.affiliation: CLL Research and Treatment Program, Hofstra Northwell School of Medicine, New Hyde Park, New York.
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Barrientos
authors.affiliation: Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: University of California San Diego, Moores Cancer Center, La Jolla, California.
authors.forename: Januario E
authors.initials: JE
authors.lastname: Castro
authors.affiliation: Division of Hematology-Oncology, Weill Cornell Medical College, New York, New York.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.affiliation: John Vane Cancer Centre, Charterhouse Square, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Gribben
authors.affiliation: Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Hill
authors.affiliation: Department of Haematology, Saint Antoine Hospital, University Pierre & Marie Curie, and Inserm UMRs938, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Hospital de la Santa Creu Sant Pau, Barcelona, Spain.
authors.forename: Carol
authors.initials: C
authors.lastname: Moreno
authors.affiliation: The University of California Irvine Chao Family Comprehensive Cancer Center, Orange, California.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: National Institutes of Health-National Cancer Institute Experimental Transplantation and Immunology Branch, Bethesda, Maryland.
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Pavletic
authors.affiliation: Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, Florida; Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida.
authors.forename: Javier
authors.initials: J
authors.lastname: Pinilla-Ibarz
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Nishitha M
authors.initials: NM
authors.lastname: Reddy
authors.affiliation: Department of Medicine, University of Washington School of Medicine and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Sorror
authors.affiliation: The Ottawa Hospital Blood and Marrow Transplant Program and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bredeson
authors.affiliation: Department of Medicine, University of Washington School of Medicine and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Paul
authors.initials: P
authors.lastname: Carpenter
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D017410:Practice Guidelines as Topic; D016879:Salvage Therapy; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents
keywords: Allogeneic hematopoietic cell transplantation; BCL-2 inhibitors; BCR inhibitors; Chronic lymphocytic leukemia