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.
|Number of pages||13|
|Journal||Clinical Cancer Research|
|State||Published - Aug 15 2019|
Bibliographical noteFunding Information:
Novartis, Takeda, and Nektar Therapeutics. G. Hale is an employee of Medpace. R.P. Gale is an employee of Celgene. M. Hamadani reports receiving speakers bureau honoraria from Sanofia, is a consultant/advisory board member for ADC Therapeutics, Janssen, Incyte, and reports receiving commercial research support from Astellas, Takeda, and Spectrum. S. Ganguly reports receiving speakers bureau honoraria from Seattle Genetics, is a consultant/advisory board member for Amgen, Janssen, and Kite, and reports receiving commercial research support from Daiichi Sankyo. H. Lazarus reports receiving speakers bureau honoraria from Pharmacyclics. R. Reshef is a consultant/advisory board member for Kite/Gilead, Bristol-Myers Squibb, Incyte, Pfizer, Pharmacyclics, Magenta, and Jazz Pharmaceuticals. G.C. Hildebrandt has ownership interests (including patents) at AbbVie, Aetna, Axim, Bluebird, Cardinal Health, Celgene, Cellectis, Clovis Oncology, Crisper, CVS Health, Endocyte, GW Pharmaceuticals, Idexx Labs, Immunomedics, Insys Therapeutics, Johnson & Johnson, Juno Therapeutics, Kite Pharma, Novartis, Pfizer, Procter & Gamble, Sangamo Bioscience, and Vertex Pharmaceuticals, is a consultant/advisory board member for Onyx Pharmaceuticals, Pfizer, Kite, Incyte, Jazz Pharmaceuticals, and reports receiving commercial research grants from Takeda, Jazz Pharmaceuticals, and Pharmacyclics. M. Solh has ownership interests (including patents) at Gelgene, and reports receiving speakers bureau honoraria from Amgen. M.A. Kharfan-Dabaja is a consultant/advisory board member for Pharmacyclics. N. Ghosh reports receiving speakers bureau honoraria from Pharmacyclics, Janssen, Abbvie, and Gildead, and is a consultant/advisory board member for Pharmacyclics and Janssen. A. Saad is a consultant/advisory board member for Actinium Pharma Inc. and reports receiving royalty fees from Incysus Therapeutics. B.T. Hill is a consultant/advisory board member for Pharmacyclics, Abbvie, Genentech, and AstraZeneca. N.S. Saba reports receiving speakers bureau honoraria from Pharmacyclics and Janssen, is a consultant/advisory board member for Pharmacyclics, I-Mab Biopharma, and Kyowa Kirin, and reports receiving commercial research grants from Celgene. B. Savani reports receiving speakers bureau honoraria from Sanofi Genzyme and Jazz Pharmaceuticals. J. Cerny is a consultant/advisory board member for Pfizer Inc., Incyte Inc. and Daiichi-Sankyo. M.R. Grunwald has ownership interests (including patents) at Medtronic, is a consultant/advisory board member for Agios, Abbvie, Amgen, Cardinal Health, Celgene, Incyte, Pfizer, Merck, Daiichi-Sankyo, ARIAD, and reports receiving commercial research support from Amgen, Forma Therapeutics, Incyte, Janssen, Novartis, and Genentech/Roche. J.R. Brown reports receiving speakers bureau honoraria from Janssen, Teva, and Abbvie, is a consultant/advisory board member for Abbvie, Verastem, Gilead, Acerta, Beigene, Genentech/ Roche, Juno/Celgene, Kite, Loxo, Novartis, Pfizer, Pharmacyclics, Sunesis, TG Therapeutics, and reports receiving commercial research grants from Gilead, Loxo, Sun, and Verastem, and served on data safety monitoring committees for Invectys and Morphosys. No potential conflicts of interest were disclosed by the other authors.
This work was supported by NIH grants R01CA183559-02 (to H.T. Kim). J.R. Brown acknowledges support from National Comprehensive Cancer Network, from NCI (R01CA213442 and P01CA206978), and from the Susan and Gary Rosenbach Fund for Lymphoma Research and the Melton Family Fund for CLL Research. The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the NCI, the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement (4U10HL069294) from NHLBI and NCI; a contract (HHSH250201200016C) with Health Resources and Services Administration (HRSA/DHHS); two 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., 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, 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., Novartis Pharmaceuticals Corporation, Otsuka Pharmaceutical Co, Ltd., 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.
© 2019 American Association for Cancer Research.
ASJC Scopus subject areas
- Cancer Research