External validation of International Prognostic Score for asymptomatic early stage chronic lymphocytic leukaemia and proposal of an alternative score

Abstract

Summary 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.

Comparative analysis of international prognostic index for chronic lymphocytic leukemia, progression-risk score, and MD Anderson Cancer Center 2011 score - a single center experience

“…It successfully discriminates patients in early-stage CLL considering TTFT using only 3 variables: IGHV mutational status, ALC > 15x10 9 /L, and palpable lymph nodes. Smolej et al even proposed modified IPS-E called AIPS-E containing IGHV mutational status, FISH, and ALC [34].…”

Chemoimmunotherapy in the First-Line Treatment of Chronic Lymphocytic Leukaemia: Dead Yet, or Alive and Kicking?

“…The majority of CLL patients have an indolent, asymptomatic course of the disease, while approximately 30-40% sooner or later require therapeutic intervention due to bone marrow failure, massive/progressive organomegaly, or systemic symptoms [3,4,7,13,14]. As the vast majority of CLL patients are nowadays diagnosed with early asymptomatic disease corresponding to Binet A/Rai 0-I clinical stages [15,16], it is valuable to refine an individual patient's prognosis concerning the future risk of progression and treatment. There are numerous prognostic factors correlating with progressive clinical course in CLL but the mutational status of the immunoglobulin heavy chain variable region (IGHV) and cytogenetic aberrations detected by fluorescent in situ hybridisation (FISH) clearly belong to the most powerful ones [17][18][19][20]: patients with unmutated IGHV and/or unfavourable cytogenetic findings (deletion 11q or 17p) are much more likely to have progressive disease course.…”

“…Robust and externally validated systems include the CLL IPI project, the Barcelona-Brno score, and the MD Anderson nomogram [22][23][24]. Additionally, for patients diagnosed in Binet A stage, recently, two externally validated prognostic models have been developed based on the combination of IGVH/FISH with more traditional parameters such as absolute lymphocyte count and/or palpable lymphadenopathy [15,16,25,26]. More recently, complex karyotype (presence of ≥3 cytogenetic changes) has emerged as a potentially strong prognostic/predictive factor for unfavourable outcome, including the development of Richter s transformation [27][28][29][30]; however, more validation using data from prospective clinical trials is needed to verify its classification (e.g., three vs. five changes as the cut-off) and prognostic/predictive value [31,32].…”

Validation of the Alternative International Prognostic Score‐E (AIPS‐E): Analysis of Binet stage A chronic lymphocytic leukemia patients enrolled into the O‐CLL1‐GISL protocol

“…Condoluci et al 1 IPS-E (AIPS-E), in a cohort of 388 Binet stage cases in which the presence of palpable lymph-nodes as a predictor is substituted for by that of del(11q)/del(17p). 2 This approach may overcome the individual inter-observer variability in the evaluation of slightly enlarged external lymph nodes. Here, AIPS-E and IPS-E were evaluated in an independent cohort of newly diagnosed and non-referred Binet stage A CLL patients enrolled in the O-CLL1-GISL protocol, and the conclusion was reached that both scores are capable of an accurate prediction of the subsequent course of early stages CLL patients.…”

“…Patients were grouped into low-risk (score 0), intermediate-risk (score 1), and high-risk (score 2-3) (Table 1). 2…”