Prognosis Assessment of Early-Stage Chronic Lymphocytic Leukemia: Are We Ready to Predict Clinical Evolution Without a Crystal Ball?

BACKGROUND: The discovery of new biologic variables with high prognostic effect has been accompanied by the emergence of different prognostic indexes (PIs) to assess the time to first treatment in patients with early-stage (Binet A) chronic lymphocytic leukemia (CLL). The present study compared the prognostic value of 5 PIs: CLL international prognostic index (CLL-IPI), Barcelona-Brno, international prognostic score-A (IPS-A), CLL-01, and a tailored approach. PATIENTS AND METHODS: We applied the 5 PIs to a cohort of 428 unselected patients with Binet A CLL from a multicenter Spanish database with clinical and biologic information available. The predictive value of the scores was assessed using Harrell's concordance index (C index) and area under the receiver operating characteristic curve (AUC). RESULTS: We found a significant association between time to first treatment and risk subgroups for all 5 PIs used. The most accurate PI was the IPS-A (C-index, 0.72; AUC, 0.76), closely followed by CLL-01 (C-index, 0.69; AUC, 0.70), CLL-IPI (C-index, 0.69; AUC, 0.69), Barcelona-Brno (C-index, 0.67; AUC, 0.69), and the tailored approach (C-index, 0.61 and 0.58; AUC, 0.58 and 0.54). CONCLUSIONS: The concordance between the PIs was low (44%), suggesting that although all these PIs improve clinical staging and help physicians in routine clinical practice, it will be necessary to harmonize larger cohorts of patients to define the best PI for treatment decision-making in the real world.

Cost-utility analysis of idelalisib in combination with rituximab in relapsed or refractory chronic lymphocytic leukaemia.

OBJECTIVE: To evaluate the incremental cost-utility ratio (ICUR) of idelalisib in combination with rituximab (IR) versus rituximab monotherapy (R) in the treatment of patients with relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL), from the Spanish National Health System (NHS) perspective. METHODS: A partitioned survival Markov model for a lifetime horizon (30 years) was developed to estimate costs (€, 2016) and quality-adjusted life years (QALY) with IR and R. Initial cohort included patients with CLL receiving a second or subsequent line (2L) of treatment with IR or R. Survival data were based on CLL clinical trial. Drug, administration, monitoring, adverse events and clinical management of CLL costs were included in the model. Costs and outcomes were discounted using a 3% annually. Deterministic and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Compared to R, 2L IR treatment resulted in QALY gain of 3.147 (4.965 versus 1.818). Total costs were €118 254 for IR versus €23 874 for R. ICUR was €29 990/QALY gained with IR versus R. In the PSA, IR was cost-effective in 78% of iterations using a threshold of €45 000/QALY. CONCLUSION: IR can be considered a cost-effective treatment compared to R, in the treatment of R/R CLL patients for the Spanish NHS.

Characterization of mothers at risk of delivery at the limit of viability and factors related to infant survival.

OBJECTIVES: To determine the sociodemographic and clinical characteristics of mothers of infants at the limit of viability and to know the perinatal factors associated to infants' survival. METHOD: Single-center cohort study of mothers and newborns assisted in our tertiary care center (2004-2010). Demographic and perinatal variables were compared between mothers who gave birth ≤26 weeks GA and the general population. The association between perinatal factors and neonatal survival was studied by Cox regression analysis. RESULTS: Mothers of newborns ≤26 weeks (n = 136) had less education and pregnancy control. They had more frequently assisted reproductive technologies (ART) (5.2% versus 2.3%; p< 0.05), multiple gestations (16.6% versus 2.1%; p < 0.05), pregnancy complications and C-section (39.7% versus 13.4%; p < 0.001). After correcting for confounders, the perinatal factors independently associated with a variation in the risk of mortality were the administration of antenatal steroid [aHR (95%CI): 0.465 (0.254-0.853), p = 0.013], singleton pregnancy [aHR (95%CI): 0.482 (0.279-0.834), p = 0.009], infant's temperature on admission [aHR (95%CI): 0.642 (0.426-0.968), p = 0.035] and CRIB score [aHR (95%CI): 1.151 (1.058-1.251), p = 0.001]. CONCLUSIONS: Mothers of preterm infants at the limit of viability had more ART, multiple pregnancies, obstetrical complications and C-section. Infants' survival was independently associated to antenatal steroids, singleton pregnancy, temperature on admission and CRIB score.

High resolution melting analysis for JAK2 Exon 14 and Exon 12 mutations: a diagnostic tool for myeloproliferative neoplasms.

JAK2 mutations are important criteria for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms. We aimed to assess JAK2 exon 14 and exon 12 mutations by high-resolution melting (HRM) analysis, which allows variation screening. The exon 14 analysis included 163 patients with polycythemia vera, secondary erythrocytoses, essential thrombocythemia, or secondary thrombocytoses, and 126 healthy subjects. The study of exon 12 included 40 JAK2 V617F-negative patients (nine of which had polycythemia vera, and 31 with splanchnic vein thrombosis) and 30 healthy subjects. HRM analyses of JAK2 exons 14 and 12 gave analytical sensitivities near 1% and both intra- and interday coefficients of variation of less than 1%. For HRM analysis of JAK2 exon 14 in polycythemia vera and essential thrombocythemia, clinical sensitivities were 93.5% and 67.9%, clinical specificities were 98.8% and 97.0%, positive predictive values were 93.5% and 79.2%, and negative predictive values were 98.8% and 94.6, respectively. Correlations were observed between the results from HRM and three commonly used analytical methods. The JAK2 exon 12 HRM results agreed completely with those from sequencing analysis, and the three mutations in exon 12 were detected by both methods. Hence, HRM analysis of exons 14 and 12 in JAK2 shows better diagnostic values than three other routinely used methods against which it was compared. In addition, HRM analysis has the advantage of detecting unknown mutations.