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3. Safety and quality of cystectomy and pelvic lymph node dissection after neoadjuvant durvalumab and cisplatin/gemcitabine.

Author

Afferi, Luca, Spahn, Martin, Hayoz, Stefanie, Strebel, Räto T., Rothschild, Sacha I., Seifert, Helge, Özdemir, Berna C., Kiss, Bernhard, Maletzki, Philipp, Engeler, Daniel, Wirth, Gregory, Hadaschik, Boris, Lucca, Ilaria, John, Hubert, Sauer, Andreas, Müntener, Michael, Bubendorf, Lukas, Schneider, Martina, Musilova, Jana, and Petrausch, Ulf

Subjects
CANCER chemotherapy, LYMPHADENECTOMY, SURGICAL complications, NEOADJUVANT chemotherapy, PATIENTS' rights
Abstract

Objective: To report on the surgical safety and quality of pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and PLND for muscle‐invasive bladder cancer (MIBC) after neoadjuvant chemo‐immunotherapy. Patients and Methods: The Swiss Group for Clinical Cancer Research (SAKK) 06/17 was an open‐label single‐arm phase II trial including 61 cisplatin‐fit patients with clinical stage (c)T2–T4a cN0–1 operable urothelial MIBC or upper urinary tract cancer. Patients received neoadjuvant cisplatin/gemcitabine and durvalumab followed by surgery. Prospective quality assessment of surgeries was performed via central review of intraoperative photographs. Postoperative complications were assessed using the Clavien–Dindo Classification. Data were analysed descriptively. Results: A total of 50 patients received RC and PLND. All patients received neoadjuvant chemo‐immunotherapy. The median (interquartile range) number of lymph nodes removed was 29 (23–38). No intraoperative complications were registered. Grade ≥III postoperative complications were reported in 12 patients (24%). Complete nodal dissection (100%) was performed at the level of the obturator fossa (bilaterally) and of the left external iliac region; in 49 patients (98%) at the internal iliac region and at the right external iliac region; in 39 (78%) and 38 (76%) patients at the right and left presacral level, respectively. Conclusion: This study supports the surgical safety of RC and PLND following neoadjuvant chemo‐immunotherapy in patients with MIBC. The extent and completeness of protocol‐defined PLND varies between patients, highlighting the need to communicate and monitor the surgical template. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17

Author

Cathomas, Richard, primary, Rothschild, Sacha I., additional, Hayoz, Stefanie, additional, Bubendorf, Lukas, additional, Özdemir, Berna C., additional, Kiss, Bernhard, additional, Erdmann, Andreas, additional, Aeppli, Stefanie, additional, Mach, Nicolas, additional, Strebel, Räto T., additional, Hadaschik, Boris, additional, Berthold, Dominik, additional, John, Hubert, additional, Zihler, Deborah, additional, Schmid, Mathias, additional, Alborelli, Ilaria, additional, Schneider, Martina, additional, Musilova, Jana, additional, Spahn, Martin, additional, and Petrausch, Ulf, additional

Published
2023
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5. Mobilization of Hematopoietic Progenitor Cells with Standard- or Reduced-Dose Filgrastim after Vinorelbine in Multiple Myeloma Patients: A Randomized Prospective Single-Center Phase II Study

Author

Samaras, Panagiotis, Rütti, Markus F., Seifert, Burkhardt, Bachmann, Helga, Schanz, Urs, Eisenring, Maya, Renner, Christoph, Susanne Müller, Antonia Maria, Schmidt, Adrian, Mischo, Axel, Fuchs, Ivo, Bargetzi, Mario, Manz, Markus G., Stupp, Roger, Petrausch, Ulf, and Stenner-Liewen, Frank

Published
2018
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12. Figure S6 from Aberrant Lck Signal via CD28 Costimulation Augments Antigen-Specific Functionality and Tumor Control by Redirected T Cells with PD-1 Blockade in Humanized Mice

Author

Gulati, Pratiksha, primary, Rühl, Julia, primary, Kannan, Abhilash, primary, Pircher, Magdalena, primary, Schuberth, Petra, primary, Nytko, Katarzyna J., primary, Pruschy, Martin, primary, Sulser, Simon, primary, Haefner, Mark, primary, Jensen, Shawn, primary, Soltermann, Alex, primary, Jungraithmayr, Wolfgang, primary, Eisenring, Maya, primary, Winder, Thomas, primary, Samaras, Panagiotis, primary, Tabor, Annett, primary, Stenger, Rene, primary, Stupp, Roger, primary, Weder, Walter, primary, Renner, Christoph, primary, Münz, Christian, primary, and Petrausch, Ulf, primary

Published
2023
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13. supplementary figure legends from Aberrant Lck Signal via CD28 Costimulation Augments Antigen-Specific Functionality and Tumor Control by Redirected T Cells with PD-1 Blockade in Humanized Mice

Author

Gulati, Pratiksha, primary, Rühl, Julia, primary, Kannan, Abhilash, primary, Pircher, Magdalena, primary, Schuberth, Petra, primary, Nytko, Katarzyna J., primary, Pruschy, Martin, primary, Sulser, Simon, primary, Haefner, Mark, primary, Jensen, Shawn, primary, Soltermann, Alex, primary, Jungraithmayr, Wolfgang, primary, Eisenring, Maya, primary, Winder, Thomas, primary, Samaras, Panagiotis, primary, Tabor, Annett, primary, Stenger, Rene, primary, Stupp, Roger, primary, Weder, Walter, primary, Renner, Christoph, primary, Münz, Christian, primary, and Petrausch, Ulf, primary

Published
2023
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14. supplementary notes from Aberrant Lck Signal via CD28 Costimulation Augments Antigen-Specific Functionality and Tumor Control by Redirected T Cells with PD-1 Blockade in Humanized Mice

Author

Gulati, Pratiksha, primary, Rühl, Julia, primary, Kannan, Abhilash, primary, Pircher, Magdalena, primary, Schuberth, Petra, primary, Nytko, Katarzyna J., primary, Pruschy, Martin, primary, Sulser, Simon, primary, Haefner, Mark, primary, Jensen, Shawn, primary, Soltermann, Alex, primary, Jungraithmayr, Wolfgang, primary, Eisenring, Maya, primary, Winder, Thomas, primary, Samaras, Panagiotis, primary, Tabor, Annett, primary, Stenger, Rene, primary, Stupp, Roger, primary, Weder, Walter, primary, Renner, Christoph, primary, Münz, Christian, primary, and Petrausch, Ulf, primary

Published
2023
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15. Table S1 from Aberrant Lck Signal via CD28 Costimulation Augments Antigen-Specific Functionality and Tumor Control by Redirected T Cells with PD-1 Blockade in Humanized Mice

Author

Gulati, Pratiksha, primary, Rühl, Julia, primary, Kannan, Abhilash, primary, Pircher, Magdalena, primary, Schuberth, Petra, primary, Nytko, Katarzyna J., primary, Pruschy, Martin, primary, Sulser, Simon, primary, Haefner, Mark, primary, Jensen, Shawn, primary, Soltermann, Alex, primary, Jungraithmayr, Wolfgang, primary, Eisenring, Maya, primary, Winder, Thomas, primary, Samaras, Panagiotis, primary, Tabor, Annett, primary, Stenger, Rene, primary, Stupp, Roger, primary, Weder, Walter, primary, Renner, Christoph, primary, Münz, Christian, primary, and Petrausch, Ulf, primary

Published
2023
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18. EMH-Special Onkologie / Hämatologie

Author

Schneider, Christoph, primary, Petrausch, Ulf, additional, Pabst, Thomas, additional, Ritter, Adrian, additional, Omlin, Aurelius, additional, Dziarmaga, Allison, additional, and Cerny, Thomas, additional

Published
2022
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21. Perioperative chemoimmunotherapy with durvalumab for operable muscle-invasive urothelial carcinoma (MIUC): Primary analysis of the single arm phase II trial SAKK 06/17.

Author

Cathomas, Richard, primary, Rothschild, Sacha, additional, Hayoz, Stefanie, additional, Spahn, Martin, additional, Özdemir, Berna, additional, Kiss, Bernhard, additional, Erdmann, Andreas, additional, Aeppli, Stefanie, additional, Mach, Nicolas, additional, Strebel, Raeto, additional, Hadaschik, Boris A., additional, Berthold, Dominik R., additional, Pless, Miklos, additional, Zihler, Deborah, additional, Schmid, Mathias, additional, Schneider, Martina, additional, Musilova, Jana, additional, and Petrausch, Ulf, additional

Published
2022
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22. Efficacy and safety of heterologous booster vaccination with Ad26.COV2.S after BNT162b2 mRNA COVID‐19 vaccine in haemato‐oncological patients with no antibody response

Author

Reimann, Patrick, primary, Ulmer, Hanno, additional, Mutschlechner, Beatrix, additional, Benda, Magdalena, additional, Severgnini, Luciano, additional, Volgger, Andreas, additional, Lang, Theresia, additional, Atzl, Michele, additional, Huynh, Minh, additional, Gasser, Klaus, additional, Grabher, Claudia, additional, Mink, Sylvia, additional, Fraunberger, Peter, additional, Petrausch, Ulf, additional, Hartmann, Bernd, additional, and Winder, Thomas, additional

Published
2021
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25. Serological SARS‐CoV‐2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID‐19 vaccine in haematological and oncological patients

Author

Benda, Magdalena, primary, Mutschlechner, Beatrix, additional, Ulmer, Hanno, additional, Grabher, Claudia, additional, Severgnini, Luciano, additional, Volgger, Andreas, additional, Reimann, Patrick, additional, Lang, Theresia, additional, Atzl, Michele, additional, Huynh, Minh, additional, Gasser, Klaus, additional, Petrausch, Ulf, additional, Fraunberger, Peter, additional, Hartmann, Bernd, additional, and Winder, Thomas, additional

Published
2021
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28. Safety and efficacy of perioperative cisplatin/gemcitabine (cis/gem) and durvalumab (durva) for operable muscle-invasive urothelial carcinoma (MIUC): SAKK 06/17.

Author

Cathomas, Richard, primary, Rothschild, Sacha, additional, Hayoz, Stefanie, additional, Spahn, Martin, additional, Schardt, Julian, additional, Seiler, Roland, additional, Erdmann, Andreas, additional, Aeppli, Stefanie, additional, Mach, Nicolas, additional, Strebel, Raeto, additional, Hadaschik, Boris A., additional, Berthold, Dominik R., additional, Pless, Miklos, additional, Zihler, Deborah, additional, Schmid, Mathias, additional, Schneider, Martina, additional, Maniecka, Zuzanna, additional, and Petrausch, Ulf, additional

Published
2021
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32. Perioperative chemoimmunotherapy with durvalumab (Durva) in combination with cisplatin/gemcitabine (Cis/Gem) for operable muscle-invasive urothelial carcinoma (MIUC): Preplanned interim analysis of a single-arm phase II trial (SAKK 06/17).

Author

Cathomas, Richard, primary, Petrausch, Ulf, additional, Hayoz, Stefanie, additional, Schneider, Martina, additional, Schardt, Julian Andreas, additional, Seiler, Roland, additional, Erdmann, Andreas, additional, Rothschild, Sacha, additional, Aeppli, Stefanie, additional, Mach, Nicolas, additional, Strebel, Raeto, additional, Hadaschik, Boris A., additional, Berthold, Dominik R., additional, Pless, Miklos, additional, Zihler, Deborah, additional, Schmid, Mathias, additional, Biaggi Rudolf, Christine, additional, and Spahn, Martin, additional

Published
2020
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33. Efficacy and safety of heterologous booster vaccination with Ad26.COV2.S after BNT162b2 mRNA COVID‐19 vaccine in haemato‐oncological patients with no antibody response.

Author

Reimann, Patrick, Ulmer, Hanno, Mutschlechner, Beatrix, Benda, Magdalena, Severgnini, Luciano, Volgger, Andreas, Lang, Theresia, Atzl, Michele, Huynh, Minh, Gasser, Klaus, Grabher, Claudia, Mink, Sylvia, Fraunberger, Peter, Petrausch, Ulf, Hartmann, Bernd, and Winder, Thomas

Subjects
BOOSTER vaccines, ANTIBODY formation, COVID-19 vaccines, DNA vaccines, COVID-19
Abstract

Summary: Patients with haemato‐oncological malignancies are one of the high‐risk groups for a severe course in case of COVID‐19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato‐oncological patients without antibody response after double‐dose BNT162b2 messenger (m‐)RNA COVID‐19 vaccine. A total of 32 haemato‐oncological non‐responders to double‐dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double‐dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato‐oncological patients. [ABSTRACT FROM AUTHOR]

Published
2022
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34. Noninvasive rapid detection of metabolic adaptation in activated human T lymphocytes by hyperpolarized 13 C magnetic resonance

Author

Can, Emine, Mishkovsky, Mor, Yoshihara, Hikari A. I., Kunz, Nicolas, Couturier, Dominique-Laurent, Petrausch, Ulf, Doucey, Marie-Agnès, Comment, Arnaud, Mishkovsky, Mor [0000-0001-6816-7462], Comment, Arnaud [0000-0002-8484-3448], and Apollo - University of Cambridge Repository

Subjects
13/1, 692/308/575, 140/131, article, 631/92/1643
Abstract

The metabolic shift induced in human CD4+ T lymphocytes by stimulation is characterized by an upregulation of glycolysis, leading to an augmentation in lactate production. This adaptation has already been highlighted with various techniques and reported in several previous studies. We herein propose a method to rapidly and noninvasively detect the associated increase in flux from pyruvate to lactate catalyzed by lactate dehydrogenase using hyperpolarized 13C magnetic resonance, a technique which can be used for in vivo imaging. It was shown that the conversion of hyperpolarized 13C-pyruvate to 13C-lactate during the one-minute measurement increased by a mean factor of 3.6 in T cells stimulated for 5 days as compared to resting T cells. This method can be extended to other metabolic substrates and is therefore a powerful tool to noninvasively analyze T cell metabolism, possibly in vivo.

Published
2020

37. Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma

Author

Metaxas, Yannis, Rivalland, Gareth, Mauti, Laetitia A., Klingbiel, Dirk, Kao, Steven, Schmid, Sabine, Nowak, Anna K., Gautschi, Oliver, Bartnick, Tammo, Hughes, Brett G., Bouchaab, Hasna, Rothschild, Sacha I., Pavlakis, Nick, Wolleb, Sibylle, Petrausch, Ulf, O'Byrne, Kenneth, Froesch, Patrizia, Löffler-Baumann, Melanie, Pratsch-Peter, Susanne, Russell, Prudence, Mingrone, Walter, Savic, Spasenija, Thapa, Bibhusal, Früh, Martin, Pless, Miklos, von Moos, Roger, and John, Thomas

Published
2018
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38. Re-directed T cells for the treatment of fibroblast activation protein (FAP)-positive malignant pleural mesothelioma (FAPME-1)

Author

Petrausch Ulf, Schuberth Petra C, Hagedorn Christian, Soltermann Alex, Tomaszek Sandra, Stahel Rolf, Weder Walter, and Renner Christoph

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Asbestos is the main cause of MPM in industrialized countries. Even since asbestos is banned in most developed countries, the peak wave of MPM incidence is anticipated for the next years due to the long latency of asbestos induced MPM. MPM patients not eligible for surgical procedures like decortication or pleuro-pneumectomie have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. Methods/design This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x106 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor recognizing FAP which serves as target structure in MPM. At day 0 of the protocol, re-directed T cells will be injected in the pleural effusion and patients will be monitored for 48h under intermediate care conditions. AE, SAE, SADR and SUSAR will be monitored for 35 days and evaluated by an independent safety board to define any dose limiting toxicity (DLT). No further patient can be treated before the previous patient passed day 14 after T cell transfer. The protocol will be judged as save when no DLT occurred in the first 3 patients, or 1 DLT in 6 patients. Secondary objectives are feasibility and immune monitoring. Discussion Adoptive T cell transfer is a new and rapidly expanding branch of immunotherapies focusing on cancer treatment. Recently, objective responses could be observed in patients with chronic lymphatic leukemia treated with adoptively transferred CD19-specific re-directed T cells. The choice of the target antigen determines the possible on-target off-tissue toxicity of such approaches. There are reports of severe toxicity in patients who received T cells intravenously due to unexpected expression of the target antigen (on-target) in other tissues than the tumor (off-tissue). To minimize the risk of on-target off-tissue toxicity and to maximize the on-target anti-tumor effect we propose a clinical protocol with loco-regional administration of re-directed T cells. FAP-specific T cells will be directly injected in the pleural effusion of patients with MPM. Trial registration ClinicalTrials.gov (NCT01722149)

Published
2012
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41. Efficacious and save use of biosimilar filgrastim for hematopoietic progenitor cell chemo-mobilization with vinorelbine in multiple myeloma patients

Author

Maul, Julia-Tatjana, Stenner-Liewen, Frank, Seifert, Burkhardt, Pfrommer, Sarah, Petrausch, Ulf, Kiessling, Michael K, Schanz, Urs, Nair, Gayathri, Mischo, Axel, Taverna, Christian, Schmidt, Adrian, Bargetzi, Mario, Stupp, Roger, Renner, Christoph, Samaras, Panagiotis, University of Zurich, and Samaras, Panagiotis

Subjects
HPC mobilization, vinorelbine, multiple myeloma, 10219 Clinic for Gastroenterology and Hepatology, 10032 Clinic for Oncology and Hematology, 2720 Hematology, chemo mobilization, 610 Medicine & health, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), biosimilar, filgrastim
Published
2017
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42. Aberrant Lck Signal via CD28 Costimulation Augments Antigen-Specific Functionality and Tumor Control by Redirected T Cells with PD-1 Blockade in Humanized Mice

Author

Gulati, Pratiksha, primary, Rühl, Julia, additional, Kannan, Abhilash, additional, Pircher, Magdalena, additional, Schuberth, Petra, additional, Nytko, Katarzyna J., additional, Pruschy, Martin, additional, Sulser, Simon, additional, Haefner, Mark, additional, Jensen, Shawn, additional, Soltermann, Alex, additional, Jungraithmayr, Wolfgang, additional, Eisenring, Maya, additional, Winder, Thomas, additional, Samaras, Panagiotis, additional, Tabor, Annett, additional, Stenger, Rene, additional, Stupp, Roger, additional, Weder, Walter, additional, Renner, Christoph, additional, Münz, Christian, additional, and Petrausch, Ulf, additional

Published
2018
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43. Concomitant statin use does not impair the clinical outcome of patients with diffuse large B cell lymphoma treated with rituximab-CHOP

Author

Samaras, Panagiotis, Heider, Helen, Haile, Sarah, Petrausch, Ulf, Schaefer, Niklaus, Siciliano, Raffaele, Meisel, Alexander, Mischo, Axel, Zweifel, Martin, Knuth, Alexander, Stenner-Liewen, Frank, Renner, Christoph, Samaras, Panagiotis, Heider, Helen, Haile, Sarah, Petrausch, Ulf, Schaefer, Niklaus, Siciliano, Raffaele, Meisel, Alexander, Mischo, Axel, Zweifel, Martin, Knuth, Alexander, Stenner-Liewen, Frank, and Renner, Christoph

Abstract

Preclinical data indicated a detrimental effect of statins on the anti-lymphoma activity of rituximab. We evaluated the impact of concomitant statin medication on the response and survival of patients with diffuse large B cell lymphoma (DLBCL) receiving rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) as first-line therapy. Medical histories of patients with DLBCL who were treated with R-CHOP as first-line therapy were assessed for concomitant statin use, response after completion of chemotherapy, event-free survival (EFS), and overall survival (OS). Furthermore, 2-[18F]fluor-2-deoxyglucose (FDG)-PET/CT results after completion of first-line therapy were compared between the groups. Overall, 145 patients with DLBCL treated with R-CHOP from January 2001 to December 2009 were analyzed. Twenty-one (15%) patients received statins throughout therapy. Five-year EFS was 67.3% in patients without statins compared with 79% in patients receiving statins during R-CHOP (HR, 0.47; 95% CI, 0.15-1.54, p = 0.2). Five-year OS was 81.4% for patients without statins compared with 93.3% for patients taking statins (HR, 0.58; 95% CI 0.07-4.55, p = 0.6). There were no statistically significant differences in the rates of complete remissions between the two groups (75% in the non-statin group versus 86% in the statin group, p = 0.45). A trend toward a lower rate of complete metabolic responses in FDG-PET/CT after chemotherapy was seen in patients without statin medication compared with the patients taking statins (84% versus 92%, p = 0.068). Concomitant statin use had no adverse impact on response to chemotherapy, EFS, and OS in patients treated with R-CHOP for DLBCL

Published
2018

44. Pegfilgrastim reduces the length of hospitalization and the time to engraftment in multiple myeloma patients treated with melphalan 200 and auto-SCT compared with filgrastim

Author

Samaras, Panagiotis, Blickenstorfer, Marcel, Siciliano, Raffaele, Haile, Sarah, Buset, Elefteri, Petrausch, Ulf, Mischo, Axel, Honegger, Hanspeter, Schanz, Urs, Stussi, Georg, Stahel, Rolf, Knuth, Alexander, Stenner-Liewen, Frank, Renner, Christoph, Samaras, Panagiotis, Blickenstorfer, Marcel, Siciliano, Raffaele, Haile, Sarah, Buset, Elefteri, Petrausch, Ulf, Mischo, Axel, Honegger, Hanspeter, Schanz, Urs, Stussi, Georg, Stahel, Rolf, Knuth, Alexander, Stenner-Liewen, Frank, and Renner, Christoph

Abstract

To reduce the duration of neutropenia after conditioning chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT), granulocyte-colony stimulating factors (G-CSF) are commonly administered. We retrospectively evaluated the impact of pegfilgrastim compared to filgrastim on neutrophil engraftment, hospital stay, and supportive measures in patients with multiple myeloma after conditioning with Melphalan 200 (Mel200) followed by APBSCT. Ninety-two APBSCT after Mel200 treatment were performed in 72 patients between January 2006 and December 2009 at our institution. Patients received either single-dose pegfilgrastim (n = 46; 50%), or daily filgrastim (n = 46; 50%) after APBSCT (median duration of filgrastim use, 9days; range, 3-14days). Duration of neutropenia grade IV was shorter with pegfilgrastim compared with filgrastim (median, 5days (range, 3-14days) versus 6days (range, 3-9days), p = 0.0079). The length of hospitalization differed significantly (pegfilgrastim (median, 14.5days; range, 11-47days) versus filgrastim (median, 15.5days; range, 12-64days), p = 0.024). Pegfilgrastim-treated patients had less red blood cell transfusions (median, 0 transfusions (range, 0-10) versus 0.5 transfusions (range, 0-9), p = 0.00065). Pegfilgrastim was associated with reduced cost of the treatment procedure compared with filgrastim (p = 0.031). Pegfilgrastim appears to be at least equivalent to filgrastim without additional expenditure in myeloma patients treated with Mel200 and APBSCT

Published
2018

45. Maturation of tertiary lymphoid structures and recurrence of stage II and III colorectal cancer

Author

Posch, Florian, Silina, Karina, Leibl, Sebastian, Mündlein, Axel, Moch, Holger, Siebenhüner, Alexander, Samaras, Panagiotis, Riedl, Jakob, Stotz, Michael, Szkandera, Joanna, Stöger, Herbert, Pichler, Martin, Stupp, Roger, van den Broek, Maries; https://orcid.org/0000-0002-9489-3692, Schraml, Peter, Gerger, Armin, Petrausch, Ulf, Winder, Thomas, Posch, Florian, Silina, Karina, Leibl, Sebastian, Mündlein, Axel, Moch, Holger, Siebenhüner, Alexander, Samaras, Panagiotis, Riedl, Jakob, Stotz, Michael, Szkandera, Joanna, Stöger, Herbert, Pichler, Martin, Stupp, Roger, van den Broek, Maries; https://orcid.org/0000-0002-9489-3692, Schraml, Peter, Gerger, Armin, Petrausch, Ulf, and Winder, Thomas

Abstract

Tertiary lymphoid structures (TLS) are associated with favorable outcome in non-metastatic colorectal carcinoma (nmCRC), but the dynamics of TLS maturation and its association with effective anti-tumor immune surveillance in nmCRC are unclear. Here, we hypothesized that not only the number of TLS but also their composition harbors information on recurrence risk in nmCRC. In a comprehensive molecular, tissue, laboratory, and clinical analysis of 109 patients with stage II/III nmCRC, we assessed TLS numbers and degree of maturation in surgical specimens by multi-parameter immunofluorescence of follicular dendritic cell (FDC) and germinal center (GC) markers. TLS formed in most tumors and were significantly more prevalent in highly-microsatellite-instable (MSI-H) and/or BRAF-mutant nmCRC. We could distinguish three sequential TLS maturation stages which were characterized by increasing prevalence of FDCs and mature B-cells: [1] Early TLS, composed of dense lymphocytic aggregates without FDCs, [2] Primary follicle-like TLS, having FDCs but no GC reaction, and [3] Secondary follicle-like TLS, having an active GC reaction. A simple integrated TLS immunoscore reflecting these parameters identified a large subgroup of nmCRC patients with a very low risk of recurrence independently of clinical co-variables such as ECOG performance status, age, stage, and adjuvant chemotherapy. We conclude that (1) mismatch repair and BRAF mutation status are associated with the formation of TLS in nmCRC, (2) TLS formation in nmCRC follows sequential maturation steps, culminating in germinal center formation, and (3) this maturation process harbors important prognostic information on the risk of disease recurrence.

Published
2018

46. Maturation of tertiary lymphoid structures and recurrence of stage II and III colorectal cancer

Author

Posch, Florian, primary, Silina, Karina, additional, Leibl, Sebastian, additional, Mündlein, Axel, additional, Moch, Holger, additional, Siebenhüner, Alexander, additional, Samaras, Panagiotis, additional, Riedl, Jakob, additional, Stotz, Michael, additional, Szkandera, Joanna, additional, Stöger, Herbert, additional, Pichler, Martin, additional, Stupp, Roger, additional, van den Broek, Maries, additional, Schraml, Peter, additional, Gerger, Armin, additional, Petrausch, Ulf, additional, and Winder, Thomas, additional

Published
2017
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49. The maturation stage of tumoral tertiary lymphoid structures to predict recurrence risk in localized colorectal cancer.

Author

Posch, Florian, primary, Silina, Karina, additional, Petrausch, Ulf, additional, Leibl, Sebastian, additional, Muendlein, Axel, additional, Moch, Holger, additional, Siebenhuener, Alexander Rheinhard, additional, Pestalozzi, Bernhard C., additional, Riedl, Jakob M., additional, Stotz, Michael, additional, Szkandera, Joanna, additional, Stoger, Herbert, additional, Pichler, Martin, additional, Stupp, Roger, additional, Schraml, Peter, additional, Gerger, Armin, additional, and Winder, Thomas, additional

Published
2017
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