title: Managing high-risk CLL during transition to a new treatment era: stem cell transplantation or novel agents?
abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) has been considered as the treatment of choice for patients with high-risk chronic lymphocytic leukemia (HR-CLL; ie, refractory to purine analogs, short response [<24 months] to chemoimmunotherapy, and/or presence of del[17p]/TP53 mutations). Currently, treatment algorithms for HR-CLL are being challenged by the introduction of novel classes of drugs. Among them, BCR signal inhibitors (BCRi) and B-cell lymphoma 2 antagonists (BCL2a) appear particularly promising. As a result of the growing body of favorable outcome data reported for BCRi/BCL2a, uncertainty is emerging on how to advise patients with HR-CLL about indication for and timing of HSCT. This article provides an overview of currently available evidence and theoretical considerations to guide this difficult decision process. Until the risks and benefits of different treatment strategies are settled, all patients with HR-CLL should be considered for treatment with BCRi/BCL2a. For patients who respond to these agents, there are 2 treatment possibilities: (1) performing an HSCT or (2) continuing treatment with the novel drug. Individual disease-specific and transplant-related risk factors, along with patient's preferences, should be taken into account when recommending one of these treatments over the other.
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Dreger
authors.affiliation: Department Medicine I, University of Dresden, Dresden, Germany; German Bone Marrow Donor Registry, Tübingen, Germany;
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark;
authors.forename: Niels
authors.initials: N
authors.lastname: Andersen
authors.affiliation: Department Hematology and Pediatric Onco-Hematology, Istituto Nazionale dei Tumori, Milan, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.affiliation: Department Internal Medicine/Hematology, Maastricht University, Maastricht, The Netherlands;
authors.forename: Michel
authors.initials: M
authors.lastname: van Gelder
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, United Kingdom;
authors.forename: John
authors.initials: J
authors.lastname: Gribben
authors.affiliation: Department of Medicine/Hematology Unit, Karolinska Institute, Huddinge, Sweden;
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.affiliation: Service d'Hématologie, Centre Hospitalier Lyon-Sud, Lyon, France;
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Hospital de la Santa Creu Sant Pau, Barcelona, Spain;
authors.forename: Carol
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Department Medicine III, University of Ulm, Ulm, Germany; and.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: Department of Hematology, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D000465:Algorithms; D002471:Cell Transformation, Neoplastic; D002986:Clinical Trials as Topic; D003657:Decision Making; D004358:Drug Therapy / Q000379:methods; D016158:Genes, p53; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D051562:Proto-Oncogene Proteins c-bcr / Q000037:antagonists & inhibitors; D011788:Quality of Life; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr