Most patients with chronic lymphocytic leukaemia (CLL) are nowadays diagnosed without any symptoms and do not require therapy. A prognostic score identifying patients within this large group who are at high risk of disease progression would be highly beneficial. The recently published International Prognostic Score for Early asymptomatic patients (IPS-E) uses combination of absolute lymphocyte count (ALC) >15 × 109 /l, palpable lymphadenopathy, and unmutated immunoglobulin heavy-chain variable-region (IGHV) gene to predict the time to first-line therapy (TTFT). Patients at low, intermediate, and high risk had estimated 5-year TTFT of 8%, 28%, and 61%. We performed an external validation of the IPS-E score using an unselected, consecutive group of 130 Binet A patients. The 5-year TTFT was 11%, 36%, and 78% (C-statistic 0·74). Furthermore, we propose an alternative system (AIPS-E) using cytogenetic aberrations instead of palpable lymphadenopathy. This system yielded 5-year TTFT of 14%, 40%, and 72%. These results were externally validated in 388 Binet A patients from five Czech centres; the 5-year TTFT was 16%, 37%, and 80% (C-statistic 0·74). In conclusion, we have successfully validated the IPS-E score for patients with early stage CLL. In addition, we propose a modified scoring system, the AIPS-E, combining IGHV, fluorescence in situ hybridisation, and ALC.

1st Department of Medicine Haematology University General Hospital Prague Czech Republic

4th Department of Internal Medicine Haematology University Hospital and Faculty of Medicine Hradec Králové Czech Republic

Department of Haematology Oncology Center Nový Jičín Czech Republic Prague Czech Republic

Department of Haematology Oncology University Hospital Olomouc Czech Republic

Department of Haematooncology University Hospital Ostrava and Faculty of Medicine Ostrava University Ostrava Czech Republic

Department of Internal Medicine Haematology University Hospital Královské Vinohrady Prague Czech Republic

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Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48:198-206.

Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46:219-34.

Condoluci A, Terzi di Bergamo L, Langerbeins P, Hoechstetter MA, Herling CD, De Paoli L, et al. International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia. Blood. 2020;135:1859-69.

Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446-56.

Rosenquist R, Ghia P, Hadzidimitriou A, Sutton LA, Agathangelidis A, Baliakas P, et al. Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: updated ERIC recommendations. Leukemia. 2017;31:1477-81.

Rack KA, van den Berg E, Haferlach C, Beverloo HB, Costa D, Espinet B, et al. European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms. Leukemia. 2019;33:1851-67.

van den Brekel MW, Castelijns JA. What the clinician wants to know: surgical perspective and ultrasound for lymph node imaging of the neck. Cancer Imaging. 2005;5(Special Issue A):S41-9.

Baatenburg de Jong RJ, Rongen RJ, Lameris JS, Harthoorn M, Verwoerd CD, Knegt P. Metastatic neck disease. Palpation vs ultrasound examination. Arch Otolaryngol Head Neck Surg. 1989;115:689-90.

Muntanola A, Bosch F, Arguis P, Arellano-Rodrigo E, Ayuso C, Gine E, et al. Abdominal computed tomography predicts progression in patients with Rai stage 0 chronic lymphocytic leukemia. J Clin Oncol. 2007;25:1576-80.

Gentile M, Cutrona G, Molica S, Ilariucci F, Mauro FR, Di Renzo N, et al. Prospective validation of predictive value of abdominal computed tomography scan on time to first treatment in Rai 0 chronic lymphocytic leukemia patients: results of the multicenter O-CLL1-GISL study. Eur J Haematol. 2016;96:36-45.

Dohner H, Stilgenbauer S, James MR, Benner A, Weilguni T, Bentz M, et al. 11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis. Blood. 1997;89:2516-22.

Zenz T, Eichhorst B, Busch R, Denzel T, Habe S, Winkler D, et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol. 2010;28:4473-9.

Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, et al. Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood. 2018;131:2745-60.

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