Maria L Ferarri

Bio: Maria L Ferarri is an academic researcher. The author has contributed to research in topics: Myeloproliferative neoplasm & Myelofibrosis. The author has an hindex of 5, co-authored 8 publications receiving 541 citations.

Myeloproliferative Neoplasm (MPN) Symptom Assessment Form Total Symptom Score: Prospective International Assessment of an Abbreviated Symptom Burden Scoring System Among Patients With MPNs

Abstract: Purpose Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy. Patients and Methods The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Results MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P < .001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 (SD, 17.2) f...

Conventional therapeutic options have limited impact on MPN symptoms: Insights from a prospective analysis of the MPN-SAF TSS

Abstract: Background. Symptom burden in MPNs is severe and a risk factor for mortality in some disease subtypes (Blood 2010;115(9):1703-8). A recent trial comparing JAK2 treatment to best available therapy revealed that patients receiving conventional MPN therapies experienced no difference or worsening of symptoms (Blood 2011;118(21):a6501). No studies have evaluated the specific associations of conventional therapies on individual MPN symptoms using a validated patient-reported measure of symptom burden. Aims. We aimed to assess associations between conventional therapies on specific MPN symptoms using the MPN-SAF TSS (Blood 2011;118(21):a3839). Methods. Patient demographics, symptom burden and disease traits including therapies were collected from MPN patients and physicians at a single time point during therapy. MPN-SAF TSS included "worst"fatigue from the BFI and MPN-SAF items of concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss and fever. MPN-SAF TSS was calculated as the total 10-item score, reported in a range of 0 to 100 for patients completing at least 6 of the 10 items. Results. Demographics: 1433 MPN patients were prospectively enrolled, including 594 essential thrombocythemia(ET), 538 polycythemia vera(PV) and 293 myelofibrosis(MF) patients from 11 countries. Of these, 1408 patients completed at least 6 of the 10 required items. Patients were 54% female with a median age of 63.Therapies: Common therapies included hydroxyurea/hydroxycarbamide(47.7%), salicylates(43.8%), interferon/pegylated- interferon(9.4%), and phlebotomies(5.3%) with 12.6% receiving no therapy. MPN-SAF TSS variations were observed between patients receiving and not receiving each therapy, although only one reached statistical significance (Table 1). Overall Treatment Effects: When comparing the overall effects of current therapy, worst fatigue was significantly more severe among PV patients undergoing treatment as compared to patients not receiving treatment (4.5(n=497) vs. 3.4(n=30), p=0.03). Among MF patients, abdominal comfort was significantly worse among patients not receiving therapy (3.3(n=57) vs. 2.3(n=230),p=0.02) .Aspirin: ET patients receiving aspirin reported significantly less weight loss than patients not receiving salicylates (0.62(n=298) vs. 0.98(n=283),p=0.03). Additionally, aspirin among ET patients reduced pruritus (1.5(n=296) vs. 2.0(n=284),p=0.02). PV patients receiving aspirin reported more concentration difficulties than patients on a non-aspirin regimen (3.0(n=254) vs. 2.4(n=264),p=0.01). MF patients receiving aspirin reported decreased bone pain (1.5(n=58) vs. 2.4(n=228),p=0.04) and abdominal discomfort (1.9(n=58) vs. 2.7(n=229),p=0.04). Hydroxyurea/hydroxycarbamide: PV patients receiving hydroxyurea/hydroxycarbamide reported decreased itching than patients not on this therapy, although this effect was of borderline significance (2.5(n=272) vs. 3.0(n=255),p=0.05). Phlebotomies: PV patients being given phlebotomies had significantly decreased problems with concentration compared to non-phlebotomized patients (1.9(n=71) vs. 2.8(n=447),p=0.02). Interferon/pegylatedinterferon: PV patients receiving interferon therapy reported increased early satiety (3.1(n=69) vs. 2.4(n=257),p=0.04), fever (0.7(n=67) vs. 0.3(n=455), p=0.02), and MPN-SAF TSS (25.5(n=69) vs. 21.2(n=460),p=0.04) than noninterferon- receiving counterparts. Conclusions. Few significant effects in overall symptom burden were observed in patients undergoing traditional MPN therapies. Though some effects reached nominal statistical significance, a portion may be spurious given the large number of tests performed. Further studies are needed to determine whether treatments impart additional symptom burden or if patients with specific symptom characteristics are selected to receive a particular treatment. Prospective serial assessment of conventional therapy impact is ongoing as part of a new clinical trial.

Myeloproliferative Neoplasm (MPN) Symptom Assessment Form Total Symptom Score: Prospective International Assessment of an Abbreviated Symptom Burden Scoring System Among Patients With MPNs

Abstract: Purpose Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy. Patients and Methods The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Results MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P < .001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 (SD, 17.2) f...

Nestin-expressing progenitor cells: function, identity and therapeutic implications.

Abstract: The neuroepithelial stem cell protein, or Nestin, is a cytoskeletal intermediate filament initially characterized in neural stem cells. However, current extensive evidence obtained in in vivo models and humans shows presence of Nestin+ cells with progenitor and/or regulatory functions in a number of additional tissues, remarkably bone marrow. This review presents the current knowledge on the role of Nestin in essential stem cell functions, including self-renewal/proliferation, differentiation and migration, in the context of the cytoskeleton. We further discuss the available in vivo models for the study of Nestin+ cells and their progeny, their function and elusive nature in nervous system and bone marrow, and their potential mechanistic role and promising therapeutic value in preclinical models of disease. Future improved in vivo models and detection methods will allow to determine the true essence of Nestin+ cells and confirm their potential application as therapeutic target in a range of diseases.

Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis

Abstract: JAK-STAT is a rational drug target in myelofibrosis (MF) given its association with JAK2/MPL mutations and aberrant inflammatory cytokine expression. We conducted a Phase 1/2 trial of CYT387, a potent JAK1/2 inhibitor, in patients with high- or intermediate-risk primary or post-polycythemia vera/essential thrombocythemia MF. Pre-planned safety and efficacy analysis has been completed for the initial 60 patients. In the dose-escalation phase (n=21), the maximum-tolerated dose was 300 mg/day based on reversible grade 3 headache and asymptomatic hyperlipasemia. Twenty-one and 18 additional patients were accrued at two biologically effective doses, 300 mg/day and 150 mg/day, respectively. Anemia and spleen responses, per International Working Group criteria, were 59% and 48%, respectively. Among 33 patients who were red cell-transfused in the month prior to study entry, 70% achieved a minimum 12-week period without transfusions (range 4.7–>18.3 months). Most patients experienced constitutional symptoms improvement. Grade 3/4 adverse reactions included thrombocytopenia (32%), hyperlipasemia (5%), elevated liver transaminases (3%) and headache (3%). New-onset treatment-related peripheral neuropathy was observed in 22% of patients (sensory symptoms, grade 1). CYT387 is well tolerated and produces significant anemia, spleen and symptom responses in MF patients. Plasma cytokine and gene expression studies suggested a broad anticytokine drug effect.

Epidemiology of myelofibrosis, essential thrombocythemia, and polycythemia vera in the European Union.

Abstract: Background Primary myelofibrosis (PMF), essential thrombocythemia (ET), and polycythemia vera (PV) are BCR ABL-negative myeloproliferative neoplasms (MPN) Published epidemiology data are scarce, and multiple sources are needed to assess the disease burden Methods We assembled the most recent information available on the incidence and prevalence of myelofibrosis (MF), ET, and PV by conducting a structured and exhaustive literature review of the published peer-reviewed literature in EMBASE and by reviewing online documentation from disease registries and relevant health registries in European countries The search was restricted to human studies written in English or French and published between January 1, 2000, and December 6, 2012 Results Eleven articles identified from EMBASE, three online hematology or oncology registries, and two Web-based databases or reports were used to summarize epidemiological estimates for MF, PV, and ET The incidence rate of MF ranged from 01 per 100 000 per year to 1 per 100 000 per year Among the various registries, the incidence of PV ranged from 04 per 100 000 per year to 28 per 100 000 per year, while the literature estimated the range of PV incidence to be 068 per 100 000 to 26 per 100 000 per year The estimated incidence of ET was between 038 per 100 000 per year and 17 per 100 000 per year While a few studies reported on the MPNs' prevalences, it is difficult to compare them as various types of prevalence were calculated (point prevalence vs period prevalence) and standardization was made according to different populations (eg, the world population and the European population) Conclusion There is a wide variation in both prevalence and incidence estimates observed across European data sources Carefully designed studies, with standardized definitions of MPNs and complete ascertainment of patients including both primary and secondary MFs, should be conducted so that estimates of the population aimed to receive novel treatments for these neoplasms are better understood assist public health planning and provide valuable information about the burden of illness to policy makers, funding agencies, resource planners, healthcare insurers, and pharmaceutical manufacturers