Predictors of retention in care in HIV-infected patients in a large hospital cohort in Italy.

Retention in care is a key feature of the cascade of continuum of care, playing an important role in achieving therapeutic success and being crucial for reduction of HIV transmission. The aim of this study was to evaluate the rate of retention in care in a large referral centre in the North of Italy and to identify predictors associated with failed retention. All new HIV-infected subjects were consecutive enrolled from 1 January 2008 to 31 December 2014. Demographics, immune-virological status, hepatitis co-infection and timing of initiation of combined antiretroviral therapy (cART) data were collected at baseline and at the time of last observation. Failed retention in care was defined as lack of laboratory data, clinical visits and drug dispensation for more than 6 months from the last visit. Cox regression analysis was used. Multivariate analysis of variables with P<0.05 in univariate analysis was performed. We enrolled 269 patients (mean age 46.1 years). Males were 197 (73%), Italian 219 (81%) with mean length of disease of 5.1 years. cART was prescribed for 257 patients (95%). The rate of retention in care was 78.4% and the rate of virological suppression was 75%. Predictors of being loss to follow-up were foreign origin (P = 0.048), CD4+ count <200/mmc (P = 0.001) and not being treated for HIV infection (P = 0.0004). Predictors of cART efficacy were shorter duration of HIV infection and baseline HIV-RNA <100 000 copies/ml. These findings underline the necessity to improve retention in care by identifying groups at increased risk of being loss to follow-up. Retention in care of vulnerable population is crucial to reach 90-90-90 UNAIDS endpoint.

How has the cost of antiretroviral therapy changed over the years? A database analysis in Italy.

BACKGROUND: The number of human immunodeficiency virus (HIV)-related hospitalizations has decreased worldwide in recent years, due to the availability of combined antiretroviral therapies (cART). The present analysis aimed to analyse the economic, and clinical burden of HIV management, after the introduction of systematic use of cART. METHODS: Data from HIV-infected patients, treated at Policlinico San Martino Hospital in Genova (Italy) were retrospectively collected. A comparison between years 2009 and 2015 was performed. HIV-related admissions were identified by using the Diagnosis-Related Group (DRG) codes. The resource consumption of outpatient services was derived by using a modelling approach. Expenditure for drugs was also analysed, as aggregate data. RESULTS: The number of HIV-infected patients was 898 in 2009 and 1006 in 2015. Overall, the virological success rate improved from 2009 to 2015, as the percentage of patients with HIV-RNA < 50 copies/mL increased from 79 to 89% (P < 0.05). The average incidence of hospitalizations per-patient decreased from 0.30 in 2009, to 0.13 in 2015. Average expenditure per-patient decreased from €10,107 in 2009 to €9063 in 2015. CONCLUSIONS: The present analysis confirmed the role of cART in controlling HIV viral load and, consequently, in reducing hospitalizations, admissions to day-hospital and the use of outpatient services. Clinical improvements and economic savings more than compensated the investments required to treat HIV-infected patients with cART. Health Authorities should invest in modern cART supply and universal treatment, to use at best the available resources and obtain a cost-effective improvement of health in people living with HIV. Additional research, with the involvement of different centers and the use of patient-specific data, are recommended to consolidate the findings of this analysis.

Is it still worthwhile to perform quarterly cd4+ t lymphocyte cell counts on hiv-1 infected stable patients?

BACKGROUND: In the last 20 years routine T CD4+ lymphocyte (CD4+) cell count has proved to be a key factor to determine the stage of HIV infection and start or discontinue of prophylaxis for opportunistic infections. However, several studies recently showed that in stable patients on cART a quarterly CD4+ cell count monitoring results in limited (or null) clinical relevance. The research is intended to investigate whether performing quarterly CD4+ cell counts in stable HIV-1 patients is still recommendable and to provide a forecast of the cost saving that could be achieved by reducing CD4+ monitoring in such a category of patients. METHODS: The study is based on data referring to all HIV-infected patients > 18 years of age being treated at two large infectious diseases units located in the metropolitan area of Genoa, Italy. The probability of CD4+ cell counts dropping below a threshold value set at 350 cells/mm3 is assessed using confidence intervals and Kaplan-Meier survival estimates, whereas multivariate Cox analysis and logistic regression are implemented in order to identify factors associated with CD4+ cell count falls below 350 cells/mm3. RESULTS: Statistical analysis reveals that among stable patients the probability of maintaining CD4+ >350 cell/mm3 is more than 98%. Econometric models indicate that HCV co-infection and HIV-RNA values >50 copies/mL in previous examinations are associated with CD4+ falls below 350 cells/mm3. Moreover, results suggest that the cost saving that could be obtained by reducing CD4+ examinations ranges from 33 to 67%. CONCLUSIONS: Empirical findings shows that patients defined as stable at enrollment are highly unlikely to experience a CD4+ value <350 cell/mm3 in the space/arc of a year. The research supports a recommendation for annual CD4+ monitoring in stable HIV-1 patients.

Unraveling the complexity of tyrosine kinase inhibitor-resistant populations by ultra-deep sequencing of the BCR-ABL kinase domain.

In chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, tyrosine kinase inhibitor (TKI) therapy may select for drug-resistant BCR-ABL mutants. We used an ultra-deep sequencing (UDS) approach to resolve qualitatively and quantitatively the complexity of mutated populations surviving TKIs and to investigate their clonal structure and evolution over time in relation to therapeutic intervention. To this purpose, we performed a longitudinal analysis of 106 samples from 33 patients who had received sequential treatment with multiple TKIs and had experienced sequential relapses accompanied by selection of 1 or more TKI-resistant mutations. We found that conventional Sanger sequencing had misclassified or underestimated BCR-ABL mutation status in 55% of the samples, where mutations with 1% to 15% abundance were detected. A complex clonal texture was uncovered by clonal analysis of samples harboring multiple mutations and up to 13 different mutated populations were identified. The landscape of these mutated populations was found to be highly dynamic. The high degree of complexity uncovered by UDS indicates that conventional Sanger sequencing might be an inadequate tool to assess BCR-ABL kinase domain mutation status, which currently represents an important component of the therapeutic decision algorithms. Further evaluation of the clinical usefulness of UDS-based approaches is warranted.

Ten Years of Medical Informatics and Standards Support for Clinical Research in an Infectious Diseases Network.

BACKGROUND: It is 30 years since evidence-based medicine became a great support for individual clinical expertise in daily practice and scientific research. Electronic systems can be used to achieve the goal of collecting data from heterogeneous datasets and to support multicenter clinical trials. The Ligurian Infectious Diseases Network (LIDN) is a web-based platform for data collection and reuse originating from a regional effort and involving many professionals from different fields. OBJECTIVES: The objective of this work is to present an integrated system of ad hoc interfaces and tools that we use to perform pseudonymous clinical data collection, both manually and automatically, to support clinical trials. METHODS: The project comprehends different scenarios of data collection systems, according to the degree of information technology of the involved centers. To be compliant with national regulations, the last developed connection is based on the standard Clinical Document Architecture Release 2 by Health Level 7 guidelines, interoperability is supported by the involvement of a terminology service. RESULTS: Since 2011, the LIDN platform has involved more than 8,000 patients from eight different hospitals, treated or under treatment for at least one infectious disease among human immunodeficiency virus (HIV), hepatitis C virus, severe acute respiratory syndrome coronavirus 2, and tuberculosis. Since 2013, systems for the automatic transfer of laboratory data have been updating patients' information for three centers, daily. Direct communication was set up between the LIDN architecture and three of the main national cohorts of HIV-infected patients. CONCLUSION: The LIDN was originally developed to support clinicians involved in the project in the management of data from HIV-infected patients through a web-based tool that could be easily used in primary-care units. Then, the developed system grew modularly to respond to the specific needs that arose over a time span of more than 10 years.

Uncovering the expression of circPVT1 in the extracellular vesicles of acute myeloid leukemia patients.

Extracellular vesicles (EVs) act as molecular mediators in the tumor microenvironment, by shuttling information contained within malignant cells and functioning as regulators of the immune system. Circular (circ)RNAs are characterized by a closed loop-like structure that makes them more stable in the extracellular milieu and suitable to be packaged inside EVs. circPVT1 (hsa_circ_0001821) showed an oncogenic role in several cancer types and immunosuppressive properties in myeloid and lymphoid cell subsets. In this study, we characterized EVs from acute myeloid leukemia (AML) patients in terms of size, concentrations, surface markers and circPVT1 cargo. We showed that circPVT1 is overexpressed by primary blast cells from newly-diagnosed AML patients compared with hematopoietic stem-progenitor cells and is released as cell-free RNA in the plasma. We isolated EVs from the plasma of AML patients and healthy subjects by size exclusion chromatography and characterized them by nanoparticle tracking analysis. EVs from patients' plasma are larger compared with those from healthy subjects and their surface profile is characterized by higher levels of the leukemic cell markers CD133, CD105, CD49e and other immune-related epitopes, with differences according to AML molecular profile. Moreover, digital PCR analysis revealed that circPVT1 is more abundant inside EVs from the plasma of AML patients compared with healthy subjects. Our findings provide new insights on the features and content of AML EVs and suggest a role of circPVT1 in the crosstalk between AML cells and the tumor microenvironment.

Gene expression profile predicts response to the combination of tosedostat and low-dose cytarabine in elderly AML.

Tosedostat is an orally administered metalloenzyme inhibitor with antiproliferative and antiangiogenic activity against hematological and solid human cancers. Clinical activity has been demonstrated in relapsed acute myeloid leukemia (AML). Thirty-three elderly patients with AML (median age, 75 years) received 120 mg tosedostat orally once daily combined with subcutaneous low-dose cytarabine (20 mg twice per day for 10 days, up to 8 cycles), until disease progression. Induction mortality was 12%. According to an intention-to-treat analysis, the complete remission (CR) rate was 48.5%, and thus the primary end point of the study was reached (expected CR, 25%). The partial remission rate was 6.1%, with an overall response rate of 54.5%. Furthermore, 4 of 33 patients had stable disease (median: 286 days). The median progression-free survival and overall survival (OS) were 203 days and 222 days, respectively. Responding patients had a longer median OS than nonresponding patients (P = .001). A microarray analysis performed in 29 of 33 patients identified 188 genes associated with clinical response (CR vs no CR). Three of them (CD93, GORASP1, CXCL16) were validated by quantitative polymerase chain reaction, which correctly classified 83% of the patients. Specifically, CR achievement was efficiently predicted by the gene expression patterns, with an overall accuracy exceeding 90%. Finally, a negative predictive value of 100% was validated in an independent series, thus representing the first molecular predictor for clinical response to a specific combination drug treatment for AML. This trial has been registered at the European Medicines Agency and on the European Clinical Trials Database (https://www.clinicaltrialsregister.eu) as #2012-000334-19.

The Ligurian HIV Network: How Medical Informatics Standards Can Help Clinical Research.

Integrating evidence from systematic research in daily clinical practice is one of the pillars of evidence-based medicine. Electronic data capture tools simplify data collection from different centers and supports the management of multicenter clinical trials. The Ligurian HIV Network (LHN) is one such tool, originating from a regional effort to integrate clinical trial capabilities for HIV and other chronic infectious diseases. In order to manually collect a complete report of all clinical tests on patients enrolled in a trial, a strenuous human effort and the allocation of great resources would be necessary. Moreover, the risk of error in a manual system is very high. The proposed system automatically extracts clinical data from the EHR of three hospitals of the LHN in a standardized way, and enhance their re-use in clinical trials. Through dedicated questionnaires, physicians reported a strongly positive feedback about the efficacy of the platform in supporting clinical research.

HAART Prescription Support Tool for Personalized Therapy.

The importance of decision support systems is highly acknowledged as a key strategy to improve medical safety and quality of care. A strong interoperability between the hospital Electronic Health Record (EHR) and the Clinical Decision Support System (CDSS) is the key to reach a most reliable decision support, that could aid in better diagnosis, reduce medication errors and improve practitioner performances. Interoperability is granted by the use of standards for data representation and for system intercommunication. A CDSS to support HAART (Highly active antiretroviral therapy) prescription in HIV (Human Immunodeficiency Virus) naive patients was developed within the Ligurian HIV Network. GLIF3 (GuideLine Interchange Format) standard was used to represent clinical guidelines in machine interpretable format. HSSP (Healthcare Services Specification Project) DSS (Decision Support System) standard was used to develop the CDSS web service that evaluates patient's data according to the rules emerging from the GLIF representation of the guidelines. Patient's data are extracted from hospital EHR, formatted into standard vMR (virtual Medical Record) documents and sent to the DSS web service to be evaluated. The results are displayed by a client application in an intuitive way to guide physician's decisions.

Electronic Health Records: From the Management of Patients to the Research Use of Clinical Data.

Paper based medical records are still widespread in Italian hospitals and the workflow to manage outpatients' visits is critical. Too many isolated software programs coexist in hospital wards and cause confusion and disorganization. A computerized medical record that unifies all the data contained in the various applications should be of fundamental importance in supporting physician's daily activities. Moreover, with the digital clinical record, data can be re-used for research purposes. The aim of this project is to create a web application for the management of outpatient visits to the Infectious Diseases Unit of the San Martino Hospital in Genoa. In order to orchestrate all the software programs acting in the visit workflow, a client application was developed to speed up the work of the medical staff at the time of the visits, ameliorating the quantity and quality of relevant information from a clinical point of view. A further extension allows standard data exchange between the developed application and the Ligurian HIV Network, which is the main regional research platform.

Time to change the single-centre approach to management of patients with tuberculosis: a novel network platform with automatic data import and data sharing.

Time to change the single-centre approach to TB http://ow.ly/lCeM30hBcbB.

A Web Based Tool to Enhance Monitoring and Retention in Care for Tuberculosis Affected Patients.

Tuberculosis (TB) is responsible for a global epidemic. TB treatment requires long-term therapy usually with multiple drugs, which have potential side effects and interactions that may influence patients' adherence to treatment. The TB Ge network is a multi-centric web based platform that collects clinical information of TB affected patients to increase their support and retention in care. The system stores the list of all tuberculosis episodes for each patient with the related data, starting from the first visit including follow-ups clinical evaluations, laboratory tests, imaging and therapies. Data can be manually input through the web interface or can be automatically imported from hospitals Laboratory Information Systems without human intervention. Automatic data import enhances data reuse and prevents errors introduction and time wasting. The network is an implementation of the Healthcare Services Specification Project (HSSP), as the Retrieve, Locate, and Update Service (RLUS) is used to manage patients' data. Clinical data are shared through standard HL7 Clinical Document Architecture (CDA) documents. Semantic interoperability is granted by the adoption of LOINC and ATC codes.

Assessment of the interlaboratory variability and robustness of JAK2V617F mutation assays: A study involving a consortium of 19 Italian laboratories.

To date, a plenty of techniques for the detection of JAK2V617F is used over different laboratories, with substantial differences in specificity and sensitivity. Therefore, to provide reliable and comparable results, the standardization of molecular techniques is mandatory.A network of 19 centers was established to 1) evaluate the inter- and intra-laboratory variability in JAK2V617F quantification, 2) identify the most robust assay for the standardization of the molecular test and 3) allow consistent interpretation of individual patient analysis results. The study was conceived in 3 different rounds, in which all centers had to blindly test DNA samples with different JAK2V617F allele burden (AB) using both quantitative and qualitative assays.The positivity of samples with an AB < 1% was not detected by qualitative assays. Conversely, laboratories performing the quantitative approach were able to determine the expected JAK2V617F AB. Quantitative results were reliable across all mutation loads with moderate variability at low AB (0.1 and 1%; CV = 0.46 and 0.77, respectively). Remarkably, all laboratories clearly distinguished between the 0.1 and 1% mutated samples.In conclusion, a qualitative approach is not sensitive enough to detect the JAK2V617F mutation, especially at low AB. On the contrary, the ipsogen JAK2 MutaQuant CE-IVD kit resulted in a high, efficient and sensitive quantification detection of all mutation loads. This study sets the basis for the standardization of molecular techniques for JAK2V617F determination, which will require the employment of approved operating procedures and the use of certificated standards, such as the recent WHO 1st International Reference Panel for Genomic JAK2V617F.

ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia.

PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. RESULTS: Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). CONCLUSION: Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered.

A SOA-Based Solution to Monitor Vaccination Coverage Among HIV-Infected Patients in Liguria.

Vaccination in HIV-infected patients constitutes an essential tool in the prevention of the most common infectious diseases. The Ligurian Vaccination in HIV Program is a proposed vaccination schedule specifically dedicated to this risk group. Selective strategies are proposed within this program, employing ICT (Information and Communication) tools to identify this susceptible target group, to monitor immunization coverage over time and to manage failures and defaulting. The proposal is to connect an immunization registry system to an existing regional platform that allows clinical data re-use among several medical structures, to completely manage the vaccination process. This architecture will adopt a Service Oriented Architecture (SOA) approach and standard HSSP (Health Services Specification Program) interfaces to support interoperability. According to the presented solution, vaccination administration information retrieved from the immunization registry will be structured according to the specifications within the immunization section of the HL7 (Health Level 7) CCD (Continuity of Care Document) document. Immunization coverage will be evaluated through the continuous monitoring of serology and antibody titers gathered from the hospital LIS (Laboratory Information System) structured into a HL7 Version 3 (v3) Clinical Document Architecture Release 2 (CDA R2).

Budget impact analysis of sofosbuvir-based regimens for the treatment of HIV/HCV-coinfected patients in northern Italy: a multicenter regional simulation.

OBJECTIVES: Chronic hepatitis C virus (HCV) is a leading cause of hospitalization and death in populations coinfected with human immunodeficiency virus (HIV). Sofosbuvir (SOF) is a pan-genotypic drug that should be combined with other agents as an oral treatment for HCV. We performed a 5-year horizon budget impact analysis of SOF-based regimens for the management of HIV/HCV-coinfected patients. METHODS: A multicenter, prospective evaluation was conducted, involving four Italian Infectious Diseases Departments (Galliera, San Martino, Sanremo, and La Spezia). All 1,005 genotype-coinfected patients (30% cirrhotics) under observation were considered (patients in all disease-stages were considered: chronic hepatitis C, cirrhosis, transplant, hepatocellular carcinoma). Disease stage costs per patient were collected; the expected disease progression in the absence of treatment and sustained virological response (SVR) success rate for SOF-based regimens were calculated based on the literature and expert opinion. Drug prices were based on what the National Health Service paid for them. The comparison of "no treatment" disease progression costs versus the economic impact of SOF-based regimens was investigated. RESULTS: Over the following 5 years, the disease progression scenario resulted in direct costs of approximately €54 million. Assuming an SVR success rate of 90%, average SOF-based regimens cost up to €50,000 per person, resulting in a final cost of more than €56 million, so this option is not economically viable. At the average price of €12,000, SOF-based regimens, expense was €17 million, saving 68%. At this price level, the economic resources invested in treating mild to moderate fibrosis stage patients would be equal to the amount of direct costs of disease management in this stage, resulting in a valid return of investment in the short-term. CONCLUSION: Given the high rates of SVR, in the Italian Healthcare System, SOF-based regimens, price is a determinant and a predictor of the overall cost for the Hepatitis C patient's management. At the average price per therapy of €12,000 over the next 5 years, SOF-based regimens are becoming highly sustainable.

IANUA: a regional project for the determination of costs in HIV-infected patients.

HIV treatment is based on combined antiretroviral therapy (cART) which has substantially improved survival, thus resulting in an increase in patient life expectancy as well as in the cost of HIV-related medical care. Therefore, several cost effectiveness studies were implemented worldwide, with one specifically in the Liguria region (Italy), to compare the annual economic expense in this area for HIV services, and the related improvement in patients' health. The IANUA project is intended to implement both cost-effectiveness and cost-utility analysis, therefore data related to clinical indicators and perceived health status were collected, the latter using a questionnaire based on the EQ-5D-3L. Information about the antiretroviral drugs and the relative quantity that a patient withdraws from the hospital pharmacy every month were extracted from the regional "F-file". All data gathered were stored in the Ligurian HIV Network, a web platform developed by the DIBRIS - Medinfo laboratory. More than eight hundred questionnaires were collected, and data will be elaborated by economists and psychologists. The first statistical elaborations showed that, as expected, costs increased as the number of therapeutic lines increased. Moreover, the average annual costs for patients whose last CD4 values were below 200 cells/mmc corresponded to the maximum expense recorded, however, the cost for patients with final CD4 counts above 500 cells/mmc was not, as expected, the lowest found. This can be explained by the fact that stabilized patients, who had CD4 values below 500 cells/mmc, did not need very expensive care, while patients with CD4 counts above 500 cells/mmc improved their health status thanks to cART.

Quality of life of people living with HIV, preliminary results from IANUA (Investigation on Antiretroviral Therapy) study.

INTRODUCTION: The introduction of combined antiretroviral treatment (cART) has reduced HIV-associated morbidity and mortality, and changed the patients' perspective of life. As a result, Health Related Quality of Life (HRQOL) has become a crucial clinical issue. OBJECTIVE: Assessment of HRQOL in a sample of Italian patients from IANUA study. Investigate correlation between CD4 cell counts, viral load and changes in HRQOL. MATERIALS AND METHODS: EQ-5D-3L self-reported questionnaire has been used in the evaluation of HRQOL. It assesses five dimensions: "mobility," "self care," "usual activities," "pain/discomfort" and "anxiety/depression." Each dimension has three levels: no problems, some problems and extreme problems. In addition, it includes a Visual Analogue Scale (VAS) where one's own health "today" is rated from 0 "worst imaginable health" to 100 "best imaginable health." The respondents provide information on marital status, education, employment/unemployment, other treatments used in addition to HAART (1,2,3,4,5 or more) and number of hospitalizations due to HIV/AIDS. RESULTS: 684 patients completed the questionnaire: 231 females and 453 males. The mean age of the sample was 51 years (range 21-78). The mean VAS score was 69.9. 558 patients (81.5%) reported no problems in mobility. 642 patients (93.5%) had no problems in self care. 423 patients (61.8%) had no pain/discomfort while 219 had some problems. 326 patients (46.1%) had some problems in anxiety/depression. CONCLUSIONS: The analysis of self-reported questionnaires indicates that HRQOL in our sample group is not deeply affected by HIV/AIDS. The dimensions that are affected in the least are "mobility" and "self care" while the major problem is "anxiety/depression" with half of the sample reporting moderate or high level.

Chromosome abnormalities additional to the Philadelphia chromosome at the diagnosis of chronic myelogenous leukemia: pathogenetic and prognostic implications.

Additional chromosome abnormalities (ACAs) occur in less than 10% of cases at diagnosis of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). In some cases, on the basis of the persistence of the ACAs in Ph-negative cells after response to imatinib, a secondary origin of the Ph chromosome has been demonstrated. In this study, the possible prognostic value of this phenomenon was evaluated. Thirty-six Ph-positive CML patients were included in the study. In six patients, ACAs persisted after the disappearance of the Ph. A complete cytogenetic response (CCR) was obtained in five of these six patients, and five of six also had a high Sokal score. In all the other cases, ACAs disappeared together (in cases of response to therapy with imatinib) or persisted with the Ph (in cases of no response to imatinib). In the former cases, the primary origin of the Ph was demonstrated. CCR was obtained in 22 cases (17 with low to intermediate Sokal scores), while no response was observed in 8 patients (5 with a high Sokal score). Sokal score seems to maintain its prognostic value for patients in whom the Ph occurs as a primary event, but not in those in whom it occurs as a secondary one.