Christian Brieghel1, Veerle Galle2, Rudi Agius1, Caspar da Cunha-Bang1, Michael A Andersen1, Philip Vlummens2, Mattias Mattsson3,4, Richard Rosenquist5,6, Karin E Smedby7, Carmen D Herling8, Jasmin Bahlo8, Michael Hallek8, Jens D Lundgren9,10, Fritz Offner2, Carsten U Niemann1. 1. Department of Hematology, Rigshospitalet, Copenhagen, Denmark. 2. Department of Clinical Hematology, Ghent University Hospital, Ghent, Belgium. 3. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. 4. Department of Hematology, Uppsala University Hospital, Uppsala, Sweden. 5. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 6. Clinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden. 7. Department of Medicine, Karolinska Institutet, Stockholm, Sweden. 8. Department of Internal Medicine, Uniklinik Köln, Cologne, Germany. 9. Centre for Health, Immunity and Infectious Diseases (CHIP), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 10. Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Abstract
INTRODUCTION: Early-stage chronic lymphocytic leukemia (CLL) challenges specialized management and follow-up. METHODS: We developed and validated a prognostic index to identify newly diagnosed patients without need of treatment (CLL-WONT) by a training/validation approach using data on 4708 patients. Composite scores derived from weighted hazards by multivariable analysis defined CLL-WONT risk groups. RESULTS: Age (>65 years: 1 point), Binet stage (B: 2 points), lactate dehydrogenase (LDH) (>205 U/L: 1 point), absolute lymphocyte count (15-30 × 109 /L: 1 point; >30 × 109 /L; 2 points), β2-microglobulin (>4 mg/L: 1 point), IGHV mutation status (unmutated: 1 point), and 11q or 17p deletion (1 point) were independently associated with shorter time to first treatment (TTFT). Low-risk patients demonstrated 5-year TTFT of 2% by internal validation, but 7-19% by external validation. Including all patients with complete scores, the 5-year TTFT was 10% for the 756 (39%) CLL-WONT low-risk patients, and the 704 (37%) patients who were both CLL-WONT and CLL-IPI low risk demonstrated even lower 5-year TTFT (8%). CONCLUSION: We have adopted the CLL-WONT at an institution covering 1 800 000 individuals to allow patients with both low-risk CLL-WONT and CLL-IPI to be managed by primary healthcare providers, thereby prioritizing specialized hematology services for patients in dire need.
INTRODUCTION: Early-stage chronic lymphocytic leukemia (CLL) challenges specialized management and follow-up. METHODS: We developed and validated a prognostic index to identify newly diagnosed patients without need of treatment (CLL-WONT) by a training/validation approach using data on 4708 patients. Composite scores derived from weighted hazards by multivariable analysis defined CLL-WONT risk groups. RESULTS: Age (>65 years: 1 point), Binet stage (B: 2 points), lactate dehydrogenase (LDH) (>205 U/L: 1 point), absolute lymphocyte count (15-30 × 109 /L: 1 point; >30 × 109 /L; 2 points), β2-microglobulin (>4 mg/L: 1 point), IGHV mutation status (unmutated: 1 point), and 11q or 17p deletion (1 point) were independently associated with shorter time to first treatment (TTFT). Low-risk patients demonstrated 5-year TTFT of 2% by internal validation, but 7-19% by external validation. Including all patients with complete scores, the 5-year TTFT was 10% for the 756 (39%) CLL-WONT low-risk patients, and the 704 (37%) patients who were both CLL-WONT and CLL-IPI low risk demonstrated even lower 5-year TTFT (8%). CONCLUSION: We have adopted the CLL-WONT at an institution covering 1 800 000 individuals to allow patients with both low-risk CLL-WONT and CLL-IPI to be managed by primary healthcare providers, thereby prioritizing specialized hematology services for patients in dire need.
Authors: Andreas Agathangelidis; Anastasia Chatzidimitriou; Thomas Chatzikonstantinou; Cristina Tresoldi; Zadie Davis; Véronique Giudicelli; Sofia Kossida; Chrysoula Belessi; Richard Rosenquist; Paolo Ghia; Anton W Langerak; Frédéric Davi; Kostas Stamatopoulos Journal: Leukemia Date: 2022-05-25 Impact factor: 12.883