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3. FRACTION: protocol of a phase II study of Fedratinib and Nivolumab combination in patients with myelofibrosis and resistance or suboptimal response to JAK-inhibitor treatment of the German MPN study group (GSG-MPN)

Author

Isfort, Susanne, von Bubnoff, Nikolas, Al-Ali, Haifa Kathrin, Becker, Heiko, Götze, Thorsten, le Coutre, Philipp, Griesshammer, Martin, Moskwa, Claudia, Wohn, Luisa, Riedel, Johanna, Palandri, Francesca, Manz, Kirsi, Hochhaus, Andreas, Döhner, Konstanze, and Heidel, Florian H.

Published
2024
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4. ROP-ET: a prospective phase III trial investigating the efficacy and safety of ropeginterferon alfa-2b in essential thrombocythemia patients with limited treatment options

Author

Kiladjian, Jean-Jacques, Marin, Francisca Ferrer, Al-Ali, Haifa Kathrin, Alvarez-Larrán, Alberto, Beggiato, Eloise, Bieniaszewska, Maria, Breccia, Massimo, Buxhofer-Ausch, Veronika, Cerna, Olga, Crisan, Ana-Manuela, Danaila, Catalin Doru, De Stefano, Valerio, Döhner, Konstanze, Empson, Victoria, Gora-Tybor, Joanna, Griesshammer, Martin, Grosicki, Sebastian, Guglielmelli, Paola, García-Gutierrez, Valentin, Heidel, Florian H., Illés, Arpád, Tomuleasa, Ciprian, James, Chloe, Koschmieder, Steffen, Krauth, Maria-Theresa, Krejcy, Kurt, Lazaroiu, Mihaela-Cornelia, Mayer, Jiri, Nagy, Zsolt György, Nicolini, Franck-Emmanuel, Palandri, Francesca, Pappa, Vassiliki, Reiter, Andreas Johannes, Sacha, Tomasz, Schlager, Stefanie, Schmidt, Stefan, Terpos, Evangelos, Unger, Martin, Wölfler, Albert, Cirici, Blanca Xicoy, and Klade, Christoph

Published
2024
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7. Diagnosis and treatment of MPN in real life: exploratory and retrospective chart review including 960 MPN patients diagnosed with ET or MF in Germany

Author

Schmidt, Andreas, Bernhardt, Christiane, Bürkle, Dieter, Fries, Stefan, Hannig, Carla V., Jentsch-Ullrich, Kathleen, Josting, Andreas, Kreher, Stephan, Reiser, Marcel, Steinmetz, Hans Tilman, Tesch, Hans, Terner, Stephanie, Schulte, Alexander, Crodel, Carl C., Palandri, Francesca, and Heidel, Florian H.

Published
2023
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9. Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia

Author

Tubío-Santamaría, Nuria, Jayavelu, Ashok Kumar, Schnoeder, Tina M., Eifert, Theresa, Hsu, Chen-Jen, Perner, Florian, Zhang, Qirui, Wenge, Daniela V., Hansen, Fynn M., Kirkpatrick, Joanna M., Jyotsana, Nidhi, Lane, Steven W., von Eyss, Björn, Deshpande, Aniruddha J., Kühn, Michael W. M., Schwaller, Juerg, Cammann, Clemens, Seifert, Ulrike, Ebstein, Frédéric, Krüger, Elke, Hochhaus, Andreas, Heuser, Michael, Ori, Alessandro, Mann, Matthias, Armstrong, Scott A., and Heidel, Florian H.

Published
2023
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13. Clinicohematologic and molecular response of essential thrombocythemia patients treated with pegylated interferon-α: a multi-center study of the German Study Group-Myeloproliferative Neoplasms (GSG-MPN)

Author

Stegelmann, Frank, Teichmann, Lino L., Heidel, Florian H., Crodel, Carl C., Ernst, Thomas, Kreil, Sebastian, Reiter, Andreas, Otten, Sara, Schauer, Stefanie, Körber, Ruth-Miriam, Kricheldorf, Kim, Isfort, Susanne, Döhner, Hartmut, Brümmendorf, Tim H., Griesshammer, Martin, Döhner, Konstanze, and Koschmieder, Steffen

Published
2023
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14. Efficacy and safety of ruxolitinib in patients with newly-diagnosed polycythemia vera: futility analysis of the RuxoBEAT clinical trial of the GSG-MPN study group

Author

Koschmieder, Steffen, Isfort, Susanne, Wolf, Dominik, Heidel, Florian H., Hochhaus, Andreas, Schafhausen, Philippe, Griesshammer, Martin, Wolleschak, Denise, Platzbecker, Uwe, Döhner, Konstanze, Jost, Philipp J., Parmentier, Stefani, Schaich, Markus, von Bubnoff, Nikolas, Stegelmann, Frank, Maurer, Angela, Crysandt, Martina, Gezer, Deniz, Kortmann, Maike, Franklin, Jeremy, Frank, Julia, Hellmich, Martin, and Brümmendorf, Tim H.

Published
2023
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20. YBX1 mediates translation of oncogenic transcripts to control cell competition in AML

Author

Perner, Florian, Schnoeder, Tina M., Xiong, Yijun, Jayavelu, Ashok Kumar, Mashamba, Nomusa, Santamaria, Nuria Tubio, Huber, Nicolas, Todorova, Kristina, Hatton, Charles, Perner, Birgit, Eifert, Theresa, Murphy, Ciara, Hartmann, Maximilian, Hoell, Jessica I., Schröder, Nicolas, Brandt, Sabine, Hochhaus, Andreas, Mertens, Peter R., Mann, Matthias, Armstrong, Scott A., Mandinova, Anna, and Heidel, Florian H.

Published
2022
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22. PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

Author

Schnoeder, Tina M., Schwarzer, Adrian, Jayavelu, Ashok Kumar, Hsu, Chen-Jen, Kirkpatrick, Joanna, Döhner, Konstanze, Perner, Florian, Eifert, Theresa, Huber, Nicolas, Arreba-Tutusaus, Patricia, Dolnik, Anna, Assi, Salam A., Nafria, Monica, Jiang, Lu, Dai, Yu-Ting, Chen, Zhu, Chen, Sai-Juan, Kellaway, Sophie G., Ptasinska, Anetta, Ng, Elizabeth S., Stanley, Edouard G., Elefanty, Andrew G., Buschbeck, Marcus, Bierhoff, Holger, Brodt, Steffen, Matziolis, Georg, Fischer, Klaus-Dieter, Hochhaus, Andreas, Chen, Chun-Wei, Heidenreich, Olaf, Mann, Matthias, Lane, Steven W., Bullinger, Lars, Ori, Alessandro, von Eyss, Björn, Bonifer, Constanze, and Heidel, Florian H.

Published
2022
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24. Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms

Author

Jayavelu, Ashok Kumar, Schnöder, Tina M., Perner, Florian, Herzog, Carolin, Meiler, Arno, Krishnamoorthy, Gurumoorthy, Huber, Nicolas, Mohr, Juliane, Edelmann-Stephan, Bärbel, Austin, Rebecca, Brandt, Sabine, Palandri, Francesca, Schröder, Nicolas, Isermann, Berend, Edlich, Frank, Sinha, Amit U., Ungelenk, Martin, Hübner, Christian A., Zeiser, Robert, Rahmig, Susann, Waskow, Claudia, Coldham, Iain, Ernst, Thomas, Hochhaus, Andreas, Jilg, Stefanie, Jost, Philipp J., Mullally, Ann, Bullinger, Lars, Mertens, Peter R., Lane, Steven W., Mann, Matthias, and Heidel, Florian H.

Published
2020
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28. Frequency of infections in 948 MPN patients: a prospective multicenter patient-reported pilot study

Author

Crodel, Carl C., Jentsch-Ullrich, Kathleen, Koschmieder, Steffen, Kämpfe, Dietrich, Griesshammer, Martin, Döhner, Konstanze, Jost, Philipp J., Wolleschak, Denise, Isfort, Susanne, Stegelmann, Frank, Jilg, Stefanie, Hofmann, Verena, Auteri, Guiseppe, Rachow, Tobias, Ernst, Philipp, Brioli, Annamaria, von Lilienfeld-Toal, Marie, Hochhaus, Andreas, Palandri, Francesca, and Heidel, Florian H.

Published
2020
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30. Distinct effects of ruxolitinib and interferon-alpha on murine JAK2V617F myeloproliferative neoplasm hematopoietic stem cell populations

Author

Austin, Rebecca J., Straube, Jasmin, Bruedigam, Claudia, Pali, Gabor, Jacquelin, Sebastien, Vu, Therese, Green, Joanne, Gräsel, Julius, Lansink, Lianne, Cooper, Leanne, Lee, Shin-Jye, Chen, Nien-Tsu, Lee, Chung-Wei, Haque, Ashraful, Heidel, Florian H., D’Andrea, Richard, Hill, Geoff R., Mullally, Ann, Milsom, Michael D., Bywater, Megan, and Lane, Steven W.

Published
2020
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31. The acetyltransferase GCN5 maintains ATRA-resistance in non-APL AML

Author

Kahl, Melanie, Brioli, Annamaria, Bens, Martin, Perner, Florian, Kresinsky, Anne, Schnetzke, Ulf, Hinze, Anna, Sbirkov, Yordan, Stengel, Sven, Simonetti, Giorgia, Martinelli, Giovanni, Petrie, Kevin, Zelent, Arthur, Böhmer, Frank-Dietmar, Groth, Marco, Ernst, Thomas, Heidel, Florian H., Scholl, Sebastian, Hochhaus, Andreas, and Schenk, Tino

Published
2019
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32. Impact of comorbidities and body mass index in patients with myelofibrosis treated with ruxolitinib

Author

Breccia, Massimo, Bartoletti, Daniela, Bonifacio, Massimiliano, Palumbo, Giuseppe A., Polverelli, Nicola, Abruzzese, Elisabetta, Bergamaschi, Micaela, Tieghi, Alessia, Tiribelli, Mario, Iurlo, Alessandra, Cavazzini, Francesco, Sgherza, Nicola, Binotto, Gianni, Isidori, Alessandro, D’Adda, Mariella, Crugnola, Monica, Bosi, Costanza, Heidel, Florian, Molica, Matteo, Scaffidi, Luigi, Cattaneo, Daniele, Latagliata, Roberto, Auteri, Giuseppe, Lemoli, Roberto M., Fanin, Renato, Russo, Domenico, Aversa, Franco, Cuneo, Antonio, Semenzato, Gianpietro, Catani, Lucia, Cavo, Michele, Vianelli, Nicola, Foà, Robin, and Palandri, Francesca

Published
2019
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33. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome

Author

Cortes, Jorge E., Heidel, Florian H., Hellmann, Andrzej, Fiedler, Walter, Smith, B. Douglas, Robak, Tadeusz, Montesinos, Pau, Pollyea, Daniel A., DesJardins, Pierre, Ottmann, Oliver, Ma, Weidong Wendy, Shaik, M. Naveed, Laird, A. Douglas, Zeremski, Mirjana, O’Connell, Ashleigh, Chan, Geoffrey, and Heuser, Michael

Published
2019
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34. Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy

Author

Cortes, Jorge E., Heidel, Florian H., Fiedler, Walter, Smith, B. Douglas, Robak, Tadeusz, Montesinos, Pau, Candoni, Anna, Leber, Brian, Sekeres, Mikkael A., Pollyea, Daniel A., Ferdinand, Roxanne, Ma, Weidong Wendy, O’Brien, Thomas, O’Connell, Ashleigh, Chan, Geoffrey, and Heuser, Michael

Published
2020
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35. Hematopoietic stem and progenitor cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia

Author

Vu, Therese, Straube, Jasmin, Porter, Amy H., Bywater, Megan, Song, Axia, Ling, Victoria, Cooper, Leanne, Pali, Gabor, Bruedigam, Claudia, Jacquelin, Sebastien, Green, Joanne, Magor, Graham, Perkins, Andrew, Chalk, Alistair M., Walkley, Carl R., Heidel, Florian H., Mukhopadhyay, Pamela, Cloonan, Nicole, Gröschel, Stefan, Mallm, Jan-Philipp, Fröhling, Stefan, Scholl, Claudia, and Lane, Steven W.

Published
2020
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37. JAK2-V617F promotes venous thrombosis through [[beta].sub.1]/[[beta].sub.2] integrin activation

Author

Edelmann, Barbel, Gupta, Nibedita, Schnoeder, Tina M., Oelschlegel, Anja M., Shahzad, Khurrum, Goldschmidt, Jurgen, Philipsen, Lars, Weinert, Soenke, Ghosh, Aniket, Saalfeld, Felix C., Nimmagadda, Subbaiah Chary, Muller, Peter, Braun- Dullaeus, Rudiger, Mohr, Juliane, Wolleschak, Denise, Kliche, Stefanie, Amthauer, Holger, Heidel, Florian H., Schraven, Burkhart, Isermann, Berend, Muller, Andreas J., and Fischer, Thomas

Subjects
Venous thrombosis -- Genetic aspects -- Development and progression -- Care and treatment, Integrins -- Health aspects, Gene expression -- Health aspects, Health care industry
Abstract

JAK2-V617F-positive chronic myeloproliferative neoplasia (CMN) commonly displays dysfunction of integrins and adhesion molecules expressed on platelets, erythrocytes, and leukocytes. However, the mechanism by which the 2 major leukocyte integrin chains, [[beta].sub.1] and [[beta].sub.2], may contribute to CMN pathophysiology remained unclear. [[beta].sub.1] ([[alpha].sub.4][[beta].sub.1]; VLA-4) and [[beta].sub.2] ([[alpha].sub.L][[beta].sub.2]; LFA-1) integrins are essential regulators for attachment of leukocytes to endothelial cells. We here showed enhanced adhesion of granulocytes from mice with JAK2-V617F knockin ([JAK2.sup.+/VF] mice) to vascular cell adhesion molecule 1- (VCAM1-) and intercellular adhesion molecule 1-coated (ICAM1-coated) surfaces. Soluble VCAM1 and ICAM1 ligand binding assays revealed increased affinity of [[beta].sub.1] and [[beta].sub.2] integrins for their respective ligands. For [[beta].sub.1] integrins, this correlated with a structural change from the low- to the high-affinity conformation induced by JAK2-V617F. JAK2- V617F triggered constitutive activation of the integrin inside-out signaling molecule Rap1, resulting in translocation toward the cell membrane. Employing a venous thrombosis model, we demonstrated that neutralizing anti-VLA-4 and anti- [[beta].sub.2] integrin antibodies suppress pathologic thrombosis as observed in [JAK2.sup.+/VF] mice. In addition, aberrant homing of [JAK2.sup.+/VF] leukocytes to the spleen was inhibited by neutralizing anti-[[beta].sub.2] antibodies and by pharmacologic inhibition of Rap1. Thus, our findings identified cross-talk between JAK2-V617F and integrin activation promoting pathologic thrombosis and abnormal trafficking of leukocytes to the spleen., Introduction Chronic myeloproliferative neoplasia (CMN) is a malignant hematopoietic disease characterized by excessive proliferation of one or more myeloid cell lineages as erythrocytes, platelets, or leukocytes. CMN comprises several sub-entities, [...]

Published
2018
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38. Diverging impact of cell fate determinants Scrib and Llgl1 on adhesion and migration of hematopoietic stem cells

Author

Dash, Banaja P., Schnöder, Tina M., Kathner, Carolin, Mohr, Juliane, Weinert, Sönke, Herzog, Carolin, Godavarthy, Parimala Sonika, Zanetti, Costanza, Perner, Florian, Braun-Dullaeus, Rüdiger, Hartleben, Björn, Huber, Tobias B., Walz, Gerd, Naumann, Michael, Ellis, Sarah, Vasioukhin, Valera, Kähne, Thilo, Krause, Daniela S., and Heidel, Florian H.

Published
2018
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42. Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms

Author

Prestipino, Alessandro, Emhardt, Alica J., Aumann, Konrad, O’Sullivan, David, Gorantla, Sivahari P., Duquesne, Sandra, Melchinger, Wolfgang, Braun, Lukas, Vuckovic, Slavica, Boerries, Melanie, Busch, Hauke, Halbach, Sebastian, Pennisi, Sandra, Poggio, Teresa, Apostolova, Petya, Veratti, Pia, Hettich, Michael, Niedermann, Gabriele, Bartholomä, Mark, Shoumariyeh, Khalid, Jutzi, Jonas S., Wehrle, Julius, Dierks, Christine, Becker, Heiko, Schmitt-Graeff, Annette, Follo, Marie, Pfeifer, Dietmar, Rohr, Jan, Fuchs, Sebastian, Ehl, Stephan, Hartl, Frederike A., Minguet, Susana, Miething, Cornelius, Heidel, Florian H., Kröger, Nicolaus, Triviai, Ioanna, Brummer, Tilman, Finke, Jürgen, Illert, Anna L., Ruggiero, Eliana, Bonini, Chiara, Duyster, Justus, Pahl, Heike L., Lane, Steven W., Hill, Geoffrey R., Blazar, Bruce R., von Bubnoff, Nikolas, Pearce, Erika L., and Zeiser, Robert

Published
2018
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43. Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation

Author

Cocciardi, Sibylle, Dolnik, Anna, Kapp-Schwoerer, Silke, Rücker, Frank G., Lux, Susanne, Blätte, Tamara J., Skambraks, Sabrina, Krönke, Jan, Heidel, Florian H., Schnöder, Tina M., Corbacioglu, Andrea, Gaidzik, Verena I., Paschka, Peter, Teleanu, Veronica, Göhring, Gudrun, Thol, Felicitas, Heuser, Michael, Ganser, Arnold, Weber, Daniela, Sträng, Eric, Kestler, Hans A., Döhner, Hartmut, Bullinger, Lars, and Döhner, Konstanze

Published
2019
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46. Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study.

Author

Palandri, Francesca, Rossi, Elena, Auteri, Giuseppe, Breccia, Massimo, Paglia, Simona, Benevolo, Giulia, Elli, Elena M., Cavazzini, Francesco, Binotto, Gianni, Tieghi, Alessia, Tiribelli, Mario, Heidel, Florian H., Bonifacio, Massimiliano, Pugliese, Novella, Caocci, Giovanni, Crugnola, Monica, Mendicino, Francesco, D'Addio, Alessandra, Tomassetti, Simona, and Martino, Bruno

Subjects
POLYCYTHEMIA vera, HYDROXYUREA, MULTIVARIATE analysis, JANUS kinases, TREATMENT effectiveness, DESCRIPTIVE statistics, RESEARCH funding, NEUROTRANSMITTER uptake inhibitors, DRUG side effects, DRUG resistance in cancer cells
Abstract

Simple Summary: The prognostic relevance of a patient achieving complete response to hydroxyurea, the predictors of response, and patients' triggers for switching to ruxolitinib are uncertain. A retrospective, real-world analysis was performed on 563 polycythemia vera patients treated with hydroxyurea for ≥12 months during an observational "PV-NET" Italian study. We investigated factors associated with a complete response to hydroxyurea and outcomes of the 397 poor responders to hydroxyurea according to whether they subsequently received ruxolitinib (n = 114) or continued hydroxyurea (n = 283). The results suggest that many PV patients receive underdosed hydroxyurea, leading to lower response and toxicity rates. In addition, many patients continued hydroxyurea despite a poor clinical or hematological response; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised. In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients' triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Molecular‐defined clonal evolution in patients with classical myeloproliferative neoplasms.

Author

Hinze, Anna, Rinke, Jenny, Crodel, Carl C., Möbius, Susanne, Schäfer, Vivien, Heidel, Florian H., Hochhaus, Andreas, and Ernst, Thomas

Subjects
MYELOPROLIFERATIVE neoplasms, SOMATIC mutation, NUCLEOTIDE sequencing, BLOOD diseases, MYELOFIBROSIS, EPIGENETICS
Abstract

Classical myeloproliferative neoplasms (MPNs) are characterized by distinct clinical phenotypes. The discovery of driver mutations in JAK2, CALR and MPL genes provided new insights into their pathogenesis. Next‐generation sequencing (NGS) identified additional somatic mutations, most frequently in epigenetic modulator genes. In this study, a cohort of 95 MPN patients was genetically characterized using targeted NGS. Clonal hierarchies of detected mutations were subsequently analysed using colony forming progenitor assays derived from single cells to study mutation acquisition. Further, the hierarchy of mutations within distinct cell lineages was evaluated. NGS revealed mutations in three epigenetic modulator genes (TET2, DNMT3A, ASXL1) as most common co‐mutations to the classical driver mutations. JAK2V617F as well as DNMT3A and TET2 mutations were detected as primary events in disease formation and most cases presented with a linear mutation pattern. Mutations appear mostly in the myeloid lineages but can also appear in lymphoid subpopulations. In one case with a double mutant MPL gene, mutations exclusively appeared in the monocyte lineage. Overall, this study confirms the mutational heterogeneity of classical MPNs and highlights the role of JAK2V617F and epigenetic modifier genes as early events in hematologic disease formation. [ABSTRACT FROM AUTHOR]

Published
2023
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48. Identifying Patients with Polycythemia Vera at Risk of Thrombosis after Hydroxyurea Initiation: The Polycythemia Vera—Advanced Integrated Models (PV-AIM) Project.

Author

Verstovsek, Srdan, Krečak, Ivan, Heidel, Florian H., De Stefano, Valerio, Bryan, Kenneth, Zuurman, Mike W., Zaiac, Michael, Morelli, Mara, Smyth, Aoife, Redondo, Santiago, Bigan, Erwan, Ruhl, Michael, Meier, Christoph, Beffy, Magali, and Kiladjian, Jean-Jacques

Subjects
POLYCYTHEMIA vera, HYDROXYUREA, ELECTRONIC health records, BIOMARKERS, THROMBOSIS
Abstract

Patients with polycythemia vera (PV) are at significant risk of thromboembolic events (TE). The PV-AIM study used the Optum® de-identified Electronic Health Record dataset and machine learning to identify markers of TE in a real-world population. Data for 82,960 patients with PV were extracted: 3852 patients were treated with hydroxyurea (HU) only, while 130 patients were treated with HU and then changed to ruxolitinib (HU-ruxolitinib). For HU-alone patients, the annualized incidence rates (IR; per 100 patients) decreased from 8.7 (before HU) to 5.6 (during HU) but increased markedly to 10.5 (continuing HU). Whereas for HU-ruxolitinib patients, the IR decreased from 10.8 (before HU) to 8.4 (during HU) and was maintained at 8.3 (after switching to ruxolitinib). To better understand markers associated with TE risk, we built a machine-learning model for HU-alone patients and validated it using an independent dataset. The model identified lymphocyte percentage (LYP), neutrophil percentage (NEP), and red cell distribution width (RDW) as key markers of TE risk, and optimal thresholds for these markers were established, from which a decision tree was derived. Using these widely used laboratory markers, the decision tree could be used to identify patients at high risk for TE, facilitate treatment decisions, and optimize patient management. [ABSTRACT FROM AUTHOR]

Published
2023
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49. Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome.

Author

Palandri, Francesca, Breccia, Massimo, Mazzoni, Camilla, Auteri, Giuseppe, Elli, Elena Maria, Trawinska, Malgorzata M., Polverelli, Nicola, Tiribelli, Mario, Benevolo, Giulia, Iurlo, Alessandra, Tieghi, Alessia, Heidel, Florian H., Caocci, Giovanni, Beggiato, Eloise, Binotto, Gianni, Cavazzini, Francesco, Miglino, Maurizio, Bosi, Costanza, Crugnola, Monica, and Bocchia, Monica

Subjects
MYELOFIBROSIS, RUXOLITINIB, POLYCYTHEMIA vera, LEUKOCYTE count, PROGNOSTIC models, REGRESSION analysis
Abstract

Background: Patients with cytopenic myelofibrosis (MF) have more limited therapeutic options and poorer prognoses compared with patients with the myeloproliferative phenotype. Aims and Methods: Prognostic correlates of cytopenic phenotype were explored in 886 ruxolitinib‐treated patients with primary/secondary MF (PMF/SMF) included in the RUX‐MF retrospective study. Cytopenia was defined as: leukocyte count <4 × 109/L and/or hemoglobin <11/<10 g/dL (males/females) and/or platelets <100 × 109/L. Results: Overall, 407 (45.9%) patients had a cytopenic MF, including 249 (52.4%) with PMF. In multivariable analysis, high molecular risk mutations (p =.04), intermediate 2/high Dynamic International Prognostic Score System (p <.001) and intermediate 2/high Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia Prognostic Model (p <.001) remained associated with cytopenic MF in the overall cohort, PMF, and SMF, respectively. Patients with cytopenia received lower average ruxolitinib at the starting (25.2 mg/day vs. 30.2 mg/day, p <.001) and overall doses (23.6 mg/day vs. 26.8 mg/day, p <.001) and achieved lower rates of spleen (26.5% vs. 34.1%, p =.04) and symptom (59.8% vs. 68.8%, p =.008) responses at 6 months compared with patients with the proliferative phenotype. Patients with cytopenia also had higher rates of thrombocytopenia at 3 months (31.1% vs. 18.8%, p <.001) but lower rates of anemia (65.6% vs. 57.7%, p =.02 at 3 months and 56.6% vs. 23.9% at 6 months, p <.001). After competing risk analysis, the cumulative incidence of ruxolitinib discontinuation at 5 years was 57% and 38% in patients with cytopenia and the proliferative phenotype (p <.001), whereas cumulative incidence of leukemic transformation was similar (p =.06). In Cox regression analysis adjusted for Dynamic International Prognostic Score System score, survival was significantly shorter in patients with cytopenia (p <.001). Conclusions: Cytopenic MF has a lower probability of therapeutic success with ruxolitinib as monotherapy and worse outcome. These patients should be considered for alternative therapeutic strategies. Cytopenic myelofibrosis has a lower probability of therapeutic success with ruxolitinib as monotherapy and worse outcome. Patients with cytopenic myelofibrosis should be considered for alternative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Published
2023
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50. Determinants of Covid19 disease and of survival after Covid19 in MPN patients treated with ruxolitinib.

Author

Palandri, Francesca, Elli, Elena M., Auteri, Giuseppe, Bonifacio, Massimiliano, Benevolo, Giulia, Heidel, Florian H., Paglia, Simona, Trawinska, Malgorzata M., Bosi, Costanza, Rossi, Elena, Tiribelli, Mario, Tieghi, Alessia, Iurlo, Alessandra, Polverelli, Nicola, Caocci, Giovanni, Binotto, Gianni, Cavazzini, Francesco, Beggiato, Eloise, Cilloni, Daniela, and Tatarelli, Caterina

Subjects
MYELOFIBROSIS, OVERALL survival, COVID-19, RUXOLITINIB
Abstract

Discussion This study provides epidemiological data on Covid19 infection in MPN patients treated with ruxolitinib, showing that 14.2% of such patients acquired the infection, with an incidence rate of 10.5 × 100 patients-years. Previous studies on Covid19 in MPN patients have included patients regardless of treatment type, with few patients treated with ruxolitinib at the time of the pandemic. Two venous thromboses occurred in Covid19 patients (all hospitalized) (IR 6.7 per 100 patient-years) and 10 thromboses occurred in non-Covid19 patients (IR 1.7 per 100 patient-years, I p i = 0.05). [Extracted from the article]

Published
2023
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