Author
Federico Sackmann
Bio: Federico Sackmann is an academic researcher. The author has contributed to research in topics: Myelofibrosis & Myeloproliferative neoplasm. The author has an hindex of 7, co-authored 16 publications receiving 463 citations.
Papers
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Mayo Clinic1, University of Paris2, VU University Amsterdam3, Erasmus University Rotterdam4, Leiden University5, Maastricht University6, Autonomous University of Madrid7, University of Freiburg8, University of Ulm9, University of Basel10, University of Angers11, University of Bordeaux12, Joseph Fourier University13, Guy's and St Thomas' NHS Foundation Trust14, British Hospital15, University of Puerto Rico16, Pompeu Fabra University17, University of Barcelona18, University of Florence19, University of Pavia20, Karolinska Institutet21, Uppsala University22
TL;DR: The MPN-SAF TSS is a concise, valid, and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospective MPN symptoms study to date.
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...
321 citations
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TL;DR: Cluster analysis from prospectively gathered symptom burden data in 1470 international patients with essential thrombocythemia, polycythemia vera, or myelofibrosis assessed for the presence of clusters and relationship to disease features and prognosis.
69 citations
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Mayo Clinic1, University of Paris2, Peking Union Medical College3, VU University Amsterdam4, Autonomous University of Madrid5, University of Ulm6, Guy's and St Thomas' NHS Foundation Trust7, Pompeu Fabra University8, University of Barcelona9, Heidelberg University10, University of Angers11, Joseph Fourier University12, University of Puerto Rico13, Imperial College London14, Uppsala University15, Erasmus University Rotterdam16, Leiden University17, Maastricht University18, University of Freiburg19, Ruhr University Bochum20, University of Basel21, University of Pavia22, Karolinska Institutet23
TL;DR: It is suggested that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms and it demonstrates that many PV symptoms remain severe independent of the number of features present.
Abstract: Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden. Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly). The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S). The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present.
48 citations
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Mayo Clinic1, Oregon Health & Science University2, VU University Medical Center3, Erasmus University Rotterdam4, University Hospital of Basel5, Centre Hospitalier Universitaire de Grenoble6, Guy's and St Thomas' NHS Foundation Trust7, University of Puerto Rico8, University of Barcelona9, University of Florence10, University of Insubria11, Peking Union Medical College12, Imperial College London13
TL;DR: The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated in this paper, where the authors evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression.
Abstract: The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression.
35 citations
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Mayo Clinic1, Oregon Health & Science University2, VU University Medical Center3, Erasmus University Rotterdam4, Loyola University Medical Center5, University Hospital of Basel6, Centre Hospitalier Universitaire de Grenoble7, Guy's and St Thomas' NHS Foundation Trust8, University of Puerto Rico9, University of Barcelona10, University of Florence11, University of Pavia12, Peking Union Medical College13, Imperial College London14
TL;DR: It is suggested that MF patients with thrombocytopenia experience greater symptomatic burden than MF patients without thromBocy topenia and may benefit from additional therapies.
16 citations
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TL;DR: In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera.
Abstract: Background Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea. Methods We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1:1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging. Results The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two g...
649 citations
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TL;DR: The current document is a revision of the International Working Group-Myeloproliferative Neoplasms Research and Treatment criteria for treatment response in myelofibrosis and represents a collaborative effort by the IWG-MRT and the European LeukemiaNet to objectively assess the value of new drugs in inducing morphologic remission or improvement in MF-associated symptomatic burden.
271 citations
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TL;DR: JAK-STAT dysregulation results in autoimmune disorders such as rheumatoid arthritis, ulcerative colitis, and Crohn disease and plays a role in the pathogenesis of myelofibrosis, polycythemia vera, and other myeloproliferative illnesses.
262 citations
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Icahn School of Medicine at Mount Sinai1, University of Michigan2, Cleveland Clinic3, Northwestern University4, University of Toronto5, University of Szeged6, Beatson West of Scotland Cancer Centre7, Stanford University8, University of California, San Diego9, Guy's and St Thomas' NHS Foundation Trust10, Mayo Clinic11, University of Texas MD Anderson Cancer Center12
TL;DR: In patients with myelofibrosis and thrombocytopenia, including those with prior anti-JAK therapy, pacritinib twice daily was more effective than BAT, including ruxolitinib, for reducing splenomegaly and symptoms.
Abstract: Importance Myelofibrosis is a hematologic malignancy characterized by splenomegaly and debilitating symptoms. Thrombocytopenia is a poor prognostic feature and limits use of Janus kinase 1 (JAK1)/Janus kinase 2 (JAK2) inhibitor ruxolitinib. Objective To compare the efficacy and safety of JAK2 inhibitor pacritinib with that of best available therapy (BAT), including ruxolitinib, in patients with myelofibrosis and thrombocytopenia. Design, Setting, and Participants For this phase 3 randomized international multicenter study—the PERSIST-2 study—of pacritinib vs BAT, 311 patients with myelofibrosis and platelet count 100 × 10 9 /L or less were recruited for analysis. Crossover from BAT was allowed after week 24 or for progression of splenomegaly. Interventions Patients were randomized 1:1:1 to pacritinib 400 mg once daily, pacritinib 200 mg twice daily, or BAT. Main Outcomes and Measures Coprimary end points were rates of patients achieving 35% or more spleen volume reduction (SVR) and 50% or more reduction in total symptom score (TSS) at week 24. Efficacy analyses were performed on the intention-to-treat efficacy population, comprising all patients with a randomization date allowing for week 24 data. Results Overall, 311 patients (mean [SD] age, 63.70 [9.08] years; 171 men [55%] and 140 women [45%]) were included in the study; 149 patients (48%) had prior ruxolitinib. The most common BAT was ruxolitinib (44 patients [45%]); 19 patients (19%) received watchful-waiting only. The intention-to-treat efficacy population included 75 patients randomized to pacritinib once daily; 74, pacritinib twice daily, and 72, BAT. Pacritinib (arms combined) was more effective than BAT for 35% or more SVR (27 patients [18%] vs 2 patients [3%]; P = .001) and had a nonsignificantly greater rate of 50% or more reduction in TSS (37 patients [25%] vs 10 patients [14%]; P = .08). Pacritinib twice daily led to significant improvements in both end points over BAT (≥35% SVR: 16 patients [22%] vs 2 patients [3%]; P = .001; ≥50% reduction in TSS: 24 patients [32%] vs 10 patients [14%]; P = .01). Clinical improvement in hemoglobin and reduction in transfusion burden were greatest with pacritinib twice daily. For pacritinib once daily, pacritinib twice daily, and BAT, the most common (>10%) grade 3 or 4 adverse events were thrombocytopenia (32 patients [31%], 34 patients [32%], 18 patients [18%]), and anemia (28 patients [27%], 23 patients [22%], 14 patients [14%]). In the pacritinib once daily, twice daily, and BAT arms, discontinuation owing to adverse events occurred in 15 patients (14%), 10 patients (9%), and 4 patients (4%). Conclusions and Relevance In patients with myelofibrosis and thrombocytopenia, including those with prior anti-JAK therapy, pacritinib twice daily was more effective than BAT, including ruxolitinib, for reducing splenomegaly and symptoms. Trial Registration clinicaltrials.gov Identifier:NCT02055781
217 citations
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TL;DR: 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 is presented.
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.
204 citations