Quantitative assessment of the CD26+ leukemic stem cell compartment in chronic myeloid leukemia: patient-subgroups, prognostic impact, and technical aspects.

Little is known about the function and phenotype of leukemic stem cells (LSCs) in chronic myeloid leukemia (CML) or about specific markers that discriminate LSCs from normal hematopoietic stem cells (HSCs). CD26 has recently been described as a specific marker of CML LSCs. In the current study, we investigated this marker in a cohort of 31 unselected CML patients. BCR/ABL1 positivity was analyzed in highly enriched stem cell fractions using fluorescence in situ hybridization (FISH) and reverse transcription PCR (RT-PCR). The proportion of CD26+ LSCs and CD26- HSCs varied considerably among the patients analyzed, and the percentage of CD26+ cells correlated with leukocyte count. The CD26 expression robustly discriminated LSCs from HSCs. This required a strict gating of the stem cell compartment. Thus, in patients with very low LSC or HSC numbers, only the highly sensitive RT-PCR method discriminated between clonal and non-clonal cells, while a robust FISH analysis required larger numbers of cells in both compartments. Finally, our data show that the numbers of CD26+ CML LSCs correlate with responses to treatment with BCR-ABL1 inhibitors.

Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States.

BACKGROUND: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib's price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness ("imatinib-first") would be cost-effective compared with the current standard of care: "physicians' choice" of initiating treatment with any one of the three TKIs. METHODS: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician's choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models' clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven's MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study's conduct. RESULTS: Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician's choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. CONCLUSION: When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP.

Chronic lymphocytic leukemia and focusing on epidemiology and management in everyday hematologic practice: recent data from the Czech Leukemia Study Group for Life (CELL).

PURPOSE: Currently, pathogenesis, new prognostic factors, or new therapy in chronic lymphocytic leukemia (CLL) are frequently discussed; however, up-to-date data concerning the incidence and the management of CLL in everyday hematologic practice are still missing. The aim of our study was to find out the accurate epidemiologic situation of CLL and the diagnostic and therapeutic preferences of hematologists in the preselect area: the South Moravian Region (1,127,718 inhabitants, white race). PATIENTS AND METHODS: The total number of 540 patients (median age at the time of diagnosis, 65 years; sex, 306 men and 234 women) who had been followed in 2008 were included in the analysis. RESULTS: In the years 2006 and 2007, the incidence of CLL was 5.8 and 6.2, respectively, per 100,000; the prevalence was 48 per 100,000. Chronic lymphocytic leukemia treatment was indicated in 194 patients (36%); 93 (17%) of them also underwent the second line of treatment. Of these 194 patients, 64 patients (33%) were given fludarabine-based regimens, and 74 patients (38%) received chlorambucil as a first line of treatment. Thirty patients were treated within clinical trials. Although the treatment was indicated in only one third of patients (36%), new prognostic factors were examined in > 50% of patients. CONCLUSION: The ascertained incidence of CLL in our region is higher than declared incidence in the past. Evidently, CLL became an often misdiagnosed and underreported disease.