Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients: Center for International Blood and Marrow Transplant Research Report

• Type of Material: Article
• Authors: Haesook T. Kim, Dana Farber Cancer Institute; Kwang Woo Ahn, Medical College of Wisconsin; Zhen-Huan Hu, Medical College of Wisconsin; Matthew S. Davids, Dana Farber Cancer Institute; Virginia O. Volpe, University of Connecticut; Joseph H. Antin, Dana Farber Cancer Institute; Mohammed L. Sorror, University of Washington; Mazyar Shadman, University of Washington; Oliver Press, Fred Hutchinson Cancer Research Center; Joseph Pidala, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; William Hogan, Mayo Clinic; Robert Negrin, Stanford Health Care; Steven Devine, CIBMTR; Joseph Uberti, Karmanos Cancer Institute; Edward Agura, Baylor University; Richard Nash, Colorado Blood Institute; Jayesh Mehta, Northwestern Medicine; Joseph McGuirk, University of Kansas; Stephen Forman, City of Hope Medical Center; Amelia Langston, Emory University; Sergio A. Giralt, Memorial Sloan Kettering Cancer Center; Miguel-Angel Perales, Memorial Sloan Kettering Cancer Center; Minoo Battiwalla, Sarah Cannon BMT Program; Gregory A. Hale, Johns Hopkins University; Robert Peter Gale, Imperial College London; David I. Marks, University Hospital Bristol NHS Trust; Mehdi Hamadani, Medical College of Wisconsin; Sid Ganguly, University of Kansas; Ulrike Bacher, University Cancer Center Hamburg; Hillard Lazarus, Case Western Reserve University; Ran Reshef, Columbia University; Gernhard C. Hildebrandt, University of Kentucky; Yoshihiro Inamoto, National Cancer Center Hospital, Tokyo, Japan; Jean-Yves Cahn, CHU Grenoble Alpes; Melhem Solh, Northside Hospital; Mohammed A. Kharfan-Dabaja, Mayo Clinic; Nilanjan Ghosh, Carolinas HealthCare System; Ayman Saad, University of Alabama Birmingham; Mahmoud Aljurf, King Faisal Specialist Hospital Center & Research; Harry C. Schouten, Maastricht University; Brian T. Hill, Cleveland Clinic; Attaphol Pawarode, University of Michigan; Tamila Kindwall-Keller, University of Virginia; Nakhle Saba, Tulane University; Edward A. Copelan, Carolinas HealthCare System; Sunita Nathan, Rush University; Amer Beitinjaneh, University of Miami; Bipin N. Savani, Vanderbilt University; Jan Cerny, UMASS Memorial Medical Center; Michael R. Grunwald, Levine Cancer Institute; Jean Yared, University of Maryland; Baldeep M. Wirk, Seattle Cancer Care Alliance; Taiga Nishihori, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Saurabh Chhabra, Medical College of Wisconsin; Richard F. Olsson, Uppsala University; Asad Bashey, Northside Hospital; Usama Gergis, New York Presbyterian Hospital; Uday Popat, University of Texas MD Anderson Cancer Center; Ronald Sobecks, Cleveland Clinic Foundation; Edwin Alyea, Dana Farber Cancer Institute; Wael Saber, Medical College of Wisconsin; Jennifer R. Brown, Dana Farber Cancer Institute
• Language: English
• Date: 2019-08-15
• Publisher: The American Association of Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 by the American Association for Cancer Research.
• Final Published Version (URL): http://dx.doi.org/10.1158/1078-0432.CCR-18-3988
• Title of Journal or Parent Work: Clinical Cancer Research
• Volume: 25
• Issue: 16
• Start Page: 5143
• End Page: 5155
• Grant/Funding Information: *Jazz Pharmaceuticals, Inc.; Juno Therapeutics; Karyopharm Therapeutics, Inc.; Kite Pharma, Inc.; Medac, GmbH; MedImmune; The Medical College of Wisconsin; *Mediware; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; *Neovii Biotech NA, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; Cerus Corporation; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; wo Grants N00014-17-1-2388 and N0014-17-1-2850 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, Inc.; *Amgen, Inc.; *Amneal Biosciences; *Angiocrine Bioscience, Inc.; The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); This work was supported by NIH grants R01CA183559–02. JRB acknowledges support from NCCN, from NCI (R01CA213442; P01CA206978) and from the Susan and Gary Rosenbach Fund for Lymphoma Research and the Melton Family Fund for CLL Research.; Novartis Pharmaceuticals Corporation; Otsuka Pharmaceutical Co, Ltd. – Japan; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick’s Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; Telomere Diagnostics, Inc.; and University of Minnesota.; a Grant/Cooperative Agreement 4U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS)
• Keywords: Science & Technology; Survival; Oncology; Stem cell transplantation; Life Sciences & Biomedicine; Follow up; Predicts; Model; CLL
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology; Biology, Biostatistics

Abstract

Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years). Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.