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ABSTRACT: Patients with mantle cell lymphoma (MCL) who experience first relapse/refractoriness can be categorized into early or late progression-of-disease (POD) groups, with a threshold of 24 months from MCL diagnosis. Bruton tyrosine kinase inhibitors (BTKi) are the established standard treatment at first relapse, but their effectiveness compared with chemoimmunotherapy (CIT) in late-POD patients remains unknown. In this international, observational cohort study, we evaluated outcomes among patients at first, late POD beyond 24 months. The primary objective was progression-free survival from the time of second-line therapy (PFS-2) of BTKi vs CIT. Overall, 385 late-POD patients were included from 10 countries. Their median age was 59 years (range, 19-70), and 77% were male. Median follow-up from the time of second-line therapy was 53 months (range, 12-144). Overall, 114 patients had second-line BTKi, whereas 271 had CIT, consisting of rituximab-bendamustine (R-B; n = 101), R-B and cytarabine (R-BAC; n = 70), or other regimens (mostly cyclophosphamide-hydroxydaunorubicin-vincristine-prednisone]- or platinum-based; n = 100). The 2 groups were balanced in clinicopathological features and median time to first relapse. Overall, BTKi was associated with significantly prolonged median PFS-2 than CIT (not reached [NR] vs 26 months, respectively; P = .0003) and overall survival (NR and 56 months, respectively; P = .03). Multivariate analyses showed that BTKi was associated with lower risk of death than R-B and other regimens (hazard ratio, 0.41 for R-B and 0.46 for others), but similar to R-BAC. These results may establish BTKi as the preferable second-line approach in patients with BTKi-naïve MCL.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células del Manto , Humanos , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Linfoma de Células del Manto/terapia , Masculino , Persona de Mediana Edad , Femenino , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto Joven , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Resultado del Tratamiento , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Progresión de la Enfermedad , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia , Estudios de CohortesRESUMEN
Minimal residual disease (MRD) analysis is a known predictive tool in mantle cell lymphoma (MCL). We describe MRD results from the Fondazione Italiana Linfomi phase 3 MCL0208 prospective clinical trial assessing lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) in the first prospective comprehensive analysis of different techniques, molecular markers, and tissues (peripheral blood [PB] and bone marrow [BM]), taken at well-defined time points. Among the 300 patients enrolled, a molecular marker was identified in 250 (83%), allowing us to analyze 234 patients and 4351 analytical findings from 10 time points. ASCT induced high rates of molecular remission (91% in PB and 83% in BM, by quantitative real-time polymerase chain reaction [RQ-PCR]). Nevertheless, the number of patients with persistent clinical and molecular remission decreased over time in both arms (up to 30% after 36 months). MRD predicted early progression and long-term outcome, particularly from 6 months after ASCT (6-month time to progression [TTP] hazard ratio [HR], 3.83; P < .001). In single-timepoint analysis, BM outperformed PB, and RQ-PCR was more reliable, while nested PCR appeared applicable to a larger number of patients (234 vs 176). To improve MRD performance, we developed a time-varying kinetic model based on regularly updated MRD results and the MIPI (Mantle Cell Lymphoma International Prognostic Index), showing an area under the ROC (Receiver Operating Characteristic) curve (AUROC) of up to 0.87 using BM. Most notably, PB reached an AUROC of up to 0.81; with kinetic analysis, it was comparable to BM in performance. MRD is a powerful predictor over the entire natural history of MCL and is suitable for models with a continuous adaptation of patient risk. The study can be found in EudraCT N. 2009-012807-25 (https://eudract.ema.europa.eu/).
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Trasplante de Células Madre Hematopoyéticas , Linfoma de Células del Manto , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Cinética , Lenalidomida , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/patología , Linfoma de Células del Manto/terapia , Neoplasia Residual , Estudios Prospectivos , Trasplante AutólogoRESUMEN
PURPOSE: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [18F]FDG PET (PET) in follicular lymphoma patients. METHODS: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS). RESULTS: Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97) and 82% (95%CI: 72%-89%) in EOI PET negative (DS1-3) and positive (DS4-5), respectively (HR 4.48; p < 0.001). When DS was associated with FLIPI-2, patients with DS3 or DS1-2 with high FLIPI-2 (3-5) experienced worse OS than patients with DS1-2 and low FLIPI-2 (1-2) (p = 0.003). CONCLUSION: This study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL. Moreover, although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1-2 patients.
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Fluorodesoxiglucosa F18 , Linfoma Folicular , Tomografía de Emisión de Positrones , Humanos , Linfoma Folicular/diagnóstico por imagen , Linfoma Folicular/terapia , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Pronóstico , Supervivencia sin Progresión , Anciano de 80 o más Años , RadiofármacosRESUMEN
The standard management for relapsed or refractory classical Hodgkin lymphoma (cHL) is salvage therapy followed by autologous stem cell transplantation (ASCT). This strategy allows almost 50% of patients to be cured. Post-ASCT maintenance treatment with brentuximab vedotin (BV) confers improved progression-free survival (PFS) to cHL patients at high risk of relapse. We investigated the outcome of 105 cHL patients receiving post-ASCT BV maintenance in the real-life setting of 23 Italian hematology centers. This population included naïve patients and those previously exposed to BV. Median follow-up was 20 months. Patients presented a median of two lines of treatment pre-ASCT, with 51% receiving BV. Twenty-nine percent of patients had at least two high-risk factors (refractory disease, complete response [CR] less than 12 months, extranodal disease at relapse), while 16% presented none. At PET-CT, a Deauville score (DS) of 1-3 was reported in 75% and 78% of pre- and post-ASCT evaluations, respectively. Grade 3-4 adverse events (AEs), mainly peripheral neuropathy, were observed in 16% of patients. Three-year PFS and overall survival (OS) were 62% and 86%, respectively. According to BV exposure, 3-year PFS and OS were 54% and 71%, respectively, for naïve and 77% and 96%, respectively, for previously exposed patients. Refractory disease (hazard ratio [HR] 4.46; p = 0.003) and post-ASCT DS 4-5 (HR 3.14; p = 0.005) were the only two factors significantly associated with PFS reduction in multivariable analysis. Post-ASCT BV maintenance is an effective, safe treatment option for cHL naïve patients and those previously exposed to BV.
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Antineoplásicos Inmunológicos/uso terapéutico , Brentuximab Vedotina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/mortalidad , Enfermedad de Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Diabetic neuropathy is the most common complication of diabetes and is frequently associated with foot ischemia and infection, but its pathogenesis is controversial. We hypothesized that proinsulin expression in peripheral blood mononuclear cells is a process relevant to this condition and could represent a link among hyperglycemia, nerve susceptibility, and diabetic foot lesions. We assessed proinsulin expression by using flow cytometry in dendritic cells from control participants and patients with type 2 diabetes with or without peripheral neuropathy or accompanied by diabetic foot. Among 32 non-neuropathic and 120 neuropathic patients with type 2 diabetes, we performed leg electromyography and found average sensory sural nerve conduction velocities of 48 ± 4 and 30 ± 4 m/s, respectively ( P < 0.03). Of those with neuropathy, 42 were without lesions, 39 had foot lesions, and 39 had neuroischemic foot lesions (allux oximetry <30 mmHg). In this well-defined diabetic population, but not in nondiabetic participants, a progressively increasing level of peripheral blood dendritic cell proinsulin expression was detected, which directly correlated with circulating TNF-α levels ( P < 0.002) and multiple conduction velocities of leg nerves ( P < 0.05). These results are consistent with the hypothesis that, in type 2 diabetes, proinsulin-expressing blood cells, possibly via their involvement in innate immunity, may play a role in diabetic peripheral neuropathy and foot lesions.-Sambataro, M., Sambado, L., Trevisiol, E., Cacciatore, M., Furlan, A., Stefani, P. M., Seganfreddo, E., Durante, E., Conte, S., Della Bella, S., Paccagnella, A., dei Tos, A. P. Proinsulin-expressing dendritic cells in type 2 neuropathic diabetic patients with and without foot lesions.
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Células Dendríticas/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Pie Diabético/metabolismo , Neuropatías Diabéticas/metabolismo , Proinsulina/metabolismo , Pie Diabético/patología , Pie Diabético/fisiopatología , Neuropatías Diabéticas/patología , Neuropatías Diabéticas/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nervio Sural/fisiopatología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM = 607, FEAM = 431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM = 2011 versus FEAM = 2013, P < .001), Sorror score ≥3 (BEAM = 15% versus FEAM = 10%, P = .017), and radiotherapy use (BEAM = 18% versus FEAM = 10%, P < .001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM = 31% versus FEAM = 44%, P < .001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM = .1 versus FEAM = .19, P < .001). Response status at day 100 post-ASCT (overall response: BEAM = 91% versus FEAM = 88%, P = .42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P = .04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carmustina/farmacología , Carmustina/uso terapéutico , Estudios de Cohortes , Citarabina/farmacología , Citarabina/uso terapéutico , Etopósido/farmacología , Etopósido/uso terapéutico , Femenino , Humanos , Italia , Linfoma/patología , Masculino , Melfalán/farmacología , Melfalán/uso terapéutico , Persona de Mediana Edad , Estudios RetrospectivosAsunto(s)
Linfadenopatía Inmunoblástica , Isocitrato Deshidrogenasa , Linfoma de Células T , Humanos , Linfadenopatía Inmunoblástica/diagnóstico , Linfadenopatía Inmunoblástica/genética , Isocitrato Deshidrogenasa/genética , Linfoma de Células T/diagnóstico , Linfoma de Células T/genética , Mutación , Estudios RetrospectivosRESUMEN
The optimal treatment of advanced sporadic Burkitt lymphoma in adults is still a matter of debate. The salutary results of pediatric therapies did open the road for improving the adult outcome. Between May 1988 and March 2009, 71 consecutive patients-46 adults, 25 children-affected by Burkitt lymphoma/leukemia were treated with the same intensive pediatric protocol alternating vincristine, adriamycine and fractionated ciclophosphamide (phase A) with high dose methotrexate and high dose cytarabine (phase B) in four Italian institutions. Eighty-nine per cent of patients were in Stage III-IV or had L3 leukemia. Complete remissions were 67/71 (94.4%), 24/25 (96%) in children, and 43/46 (93.5%) in adults. Toxic deaths were 3/71 (4.2%), all in adults. There were nine relapses (one in children, eight in adults), all but one observed early. After a median observation of 94 months (range 23-275), the Event-Free Survival rate is 92% in children and 71.7% in adults (P = 0.067). The 23 more recent adults received also rituximab, without differences in outcome as compared to patients who did not. Our experience confirms that such an intensive pediatric-derived chemotherapy is feasible and improves the long-term outcome of adults with advanced Burkitt lymphoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/mortalidad , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Burkitt/patología , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Inducción de Remisión , Rituximab , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Follicular lymphoma (FL) is an indolent hematological disease, often responsive to the first line of treatment, but characterized by repeated relapses. The therapeutic algorithm for relapsed/refractory FL patients comprises phosphatidylinositol 3-kinase inhibitors. Idelalisib showed anticancer activity, while inducing a significant rate of toxicities. Since the evidence in the literature on its use in normal clinical practice is scarce, a retrospective multicenter study was conducted to evaluate effectiveness and tolerability in a real-life context. Seventy-two patients with a median age at diagnosis of 57.2 years-mostly with an advanced stage (88.9%) and relapsed to the most recent therapy (79.1%)-were enrolled. The median number of prior therapies was three (20.8% refractory to the last therapy before idelalisib). With a median number of 4 months of treatment, the overall response rate was 41.7% (20.8% complete responses). Median disease-free survival and overall survival were achieved at 8.4 months and at 4 years, respectively. Forty-four percent of patients experienced at least one drug-related toxicity: 6.9% hematological ones and 43% non-hematological. The study confirmed that idelalisib has anticancer effectiveness and an acceptable safety profile in relapsed/refractory FL with unfavorable prognostic characteristics, even in the context of normal clinical practice.
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Patients with mantle cell lymphoma (MCL) that fail induction treatment represent a difficult-to-treat population, where no standard therapy exists. We evaluated outcomes in patients with first relapsed-refractory (r/r) MCL after upfront high dose cytarabine including standard regimens. Overall survival (OS-2) and progression-free survival (PFS-2) were estimated from the time of salvage therapy. The previously described threshold of 24 months was used to define patients as early- or late-progressors (POD). Overall, 261 r/r MCL patients were included. Second-line regimens consisted of rituximab-bendamustine (R-B, 21%), R-B and cytarabine (R-BAC, 29%), ibrutinib (19%), and others (31%). The four groups were balanced in terms of clinicopathological features. Adjusting for age and early/late-POD, patients treated with R-BAC had significantly higher complete remission (63%) than comparators. Overall, Ibrutinib and R-BAC were associated with improved median PFS-2 [24 and 25 months, respectively], compared to R-B (13) or others (7). In patients with early-POD (n = 127), ibrutinib was associated with inferior risk of death than comparators (HR 2.41 for R-B, 2.17 for others, 2.78 for R-BAC). In patients with late-POD (n = 134), no significant differences were observed between ibrutinib and bendamustine-based treatments. Ibrutinib was associated with improved outcome in early-POD patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Terapia Recuperativa , Adulto , Anciano , Resistencia a Antineoplásicos , Femenino , Estudios de Seguimiento , Humanos , Agencias Internacionales , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
OBJECTIVE: In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34+ cells predicted cardiovascular mortality at 18 months after revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker. RESEARCH DESIGN AND METHODS: The association between CD34+ cell migration and cardiovascular mortality was reassessed at 6 years after revascularization. In a new series of T2D-CLI and control subjects, immuno-sorted bone marrow CD34+ cells were profiled for miRNA expression and assessed for apoptosis and angiogenesis activity. The differentially regulated miRNA-21 and its proapoptotic target, PDCD4, were titrated to verify their contribution in transferring damaging signals from CD34+ cells to endothelial cells. RESULTS: Multivariable regression analysis confirmed that CD34+ cell migration forecasts long-term cardiovascular mortality. CD34+ cells from T2D-CLI patients were more apoptotic and less proangiogenic than those from control subjects and featured miRNA-21 downregulation, modulation of several long noncoding RNAs acting as miRNA-21 sponges, and upregulation of the miRNA-21 proapoptotic target PDCD4. Silencing miR-21 in control CD34+ cells phenocopied the T2D-CLI cell behavior. In coculture, T2D-CLI CD34+ cells imprinted naive endothelial cells, increasing apoptosis, reducing network formation, and modulating the TUG1 sponge/miRNA-21/PDCD4 axis. Silencing PDCD4 or scavenging reactive oxygen species protected endothelial cells from the negative influence of T2D-CLI CD34+ cells. CONCLUSIONS: Migration of CD34+ cells predicts long-term cardiovascular mortality in T2D-CLI patients. An altered paracrine signaling conveys antiangiogenic and proapoptotic features from CD34+ cells to the endothelium. This damaging interaction may increase the risk for life-threatening complications.
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Antígenos CD34/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2 , Células Endoteliales/fisiología , Isquemia/diagnóstico , MicroARNs/metabolismo , Proteínas de Unión al ARN/metabolismo , Adulto , Anciano , Antígenos CD34/sangre , Proteínas Reguladoras de la Apoptosis/sangre , Proteínas Reguladoras de la Apoptosis/genética , Biomarcadores/sangre , Biomarcadores/metabolismo , Células Sanguíneas/fisiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Estudios de Casos y Controles , Movimiento Celular/genética , Células Cultivadas , Enfermedad Crítica , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/mortalidad , Angiopatías Diabéticas/diagnóstico , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/mortalidad , Células Endoteliales/metabolismo , Extremidades/irrigación sanguínea , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Isquemia/sangre , Isquemia/mortalidad , Masculino , MicroARNs/sangre , MicroARNs/genética , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Proteínas de Unión al ARN/sangre , Proteínas de Unión al ARN/genética , Transducción de Señal/fisiologíaRESUMEN
Quantitative measurement of serum monoclonal protein (M-protein) is one of the most important tools for monitoring disease activity in monoclonal gammopathies. The aims of this study were to evaluate serum M-protein quantification by capillary zone electrophoresis (CZE) and to compare results with those obtained by densitometric scanning of high-resolution agarose gel electrophoresis (HRE-AGE). The evaluation was carried out on 82 samples from patients with various monoclonal gammopathies. All the suspected M-proteins were confirmed and characterised by immunofixation on agarose gel (IFE). CZE was performed on a Paragon CZE 2000 system (Beckman Coulter). Passing-Bablok regression was: y (CZE)=1.27 x(HRE-AGE)-5.21 g/L. The correlation coefficient was 0.92. Bland-Altman analysis demonstrated a mean difference of -1.83 g/L (95% CI -0.76 to -2.90) with clear evidence of a concentration-related bias. Densitometry gave higher values at low M-spikes (<20 g/L), whereas CZE gave higher values at large M-spikes (>20 g/L). The concentration-related bias was found to be independent of the immunoglobulin isotype. In conclusion, to compare previous results obtained by M-protein densitometric scanning with those obtained by direct measurement of CZE peaks, the calculation of a univocal transforming factor appears to be unreliable.