Prognostic Impact of Organomegaly in Mastocytosis: An Analysis of the European Competence Network on Mastocytosis

Johannes Lübke; Juliana Schwaab; Deborah Christen; Hanneke Oude Elberink; Bart Span; Marek Niedoszytko; Aleksandra Gorska; Magdalena Lange; Karoline V Gleixner; Emir Hadzijusufovic; Oleksii Solomianyi; Irena Angelova-Fischer; Roberta Zanotti; Massimiliano Bonifacio; Patrizia Bonadonna; Khalid Shoumariyeh; Nikolas von Bubnoff; Sabine Müller; Cecelia Perkins; Chiara Elena; Luca Malcovati; Hans Hagglund; Mattias Mattsson; Roberta Parente; Judit Varkonyi; Anna Belloni Fortina; Francesca Caroppo; Alexander Zink; Knut Brockow; Christine Breynaert; Dominique Bullens; Akif Selim Yavuz; Michael Doubek; Vito Sabato; Tanja Schug; Dietger Niederwieser; Karin Hartmann; Massimo Triggiani; Jason Gotlib; Olivier Hermine; Michel Arock; Hanneke C Kluin-Nelemans; Jens Panse; Wolfgang R Sperr; Peter Valent; Andreas Reiter; Mohamad Jawhar

doi:10.1016/j.jaip.2022.10.051

Prognostic Impact of Organomegaly in Mastocytosis: An Analysis of the European Competence Network on Mastocytosis

J Allergy Clin Immunol Pract. 2023 Feb;11(2):581-590.e5. doi: 10.1016/j.jaip.2022.10.051. Epub 2022 Nov 17.

Authors

Johannes Lübke¹, Juliana Schwaab¹, Deborah Christen², Hanneke Oude Elberink³, Bart Span⁴, Marek Niedoszytko⁵, Aleksandra Gorska⁵, Magdalena Lange⁶, Karoline V Gleixner⁷, Emir Hadzijusufovic⁸, Oleksii Solomianyi⁹, Irena Angelova-Fischer¹⁰, Roberta Zanotti¹¹, Massimiliano Bonifacio¹¹, Patrizia Bonadonna¹², Khalid Shoumariyeh¹³, Nikolas von Bubnoff¹⁴, Sabine Müller¹⁵, Cecelia Perkins¹⁶, Chiara Elena¹⁷, Luca Malcovati¹⁷, Hans Hagglund¹⁸, Mattias Mattsson¹⁸, Roberta Parente¹⁹, Judit Varkonyi²⁰, Anna Belloni Fortina²¹, Francesca Caroppo²¹, Alexander Zink²², Knut Brockow²², Christine Breynaert²³, Dominique Bullens²³, Akif Selim Yavuz²⁴, Michael Doubek²⁵, Vito Sabato²⁶, Tanja Schug²⁷, Dietger Niederwieser²⁸, Karin Hartmann²⁹, Massimo Triggiani¹⁹, Jason Gotlib¹⁶, Olivier Hermine³⁰, Michel Arock³¹, Hanneke C Kluin-Nelemans⁴, Jens Panse³², Wolfgang R Sperr⁷, Peter Valent⁷, Andreas Reiter¹, Mohamad Jawhar³³

Affiliations

¹ Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany.
² Department of Oncology, Haematology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
³ Department of Allergology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴ Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁵ Department of Allergology, Medical University of Gdańsk, Gdańsk, Poland.
⁶ Department of Dermatology, Medical University of Gdańsk, Gdańsk, Poland.
⁷ Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
⁸ Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria; Internal Medicine Small Animals, University Clinic for Small Animals, Department/University Clinic for Companion Animals and Horses, University of Veterinary Medicine, Vienna, Austria.
⁹ University Clinic for Hematology and Oncology, Kepler University Hospital, Johannes Kepler University, Linz, Austria.
¹⁰ Department of Dermatology and Venereology, Allergy Center, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.
¹¹ Section of Hematology, Department of Medicine, Verona University Hospital, Verona, Italy.
¹² Allergy Unit, Verona University Hospital, Verona, Italy.
¹³ Department of Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, Freiburg, Germany.
¹⁴ Department of Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, Freiburg, Germany; Department of Hematology and Oncology, Medical Center, University of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
¹⁵ Department of Dermatology, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.
¹⁶ Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
¹⁷ Department of Molecular Medicine and Department of Hematology Oncology, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
¹⁸ Division of Hematology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹⁹ Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
²⁰ Department of Hematology, Semmelweis University, Budapest, Hungary.
²¹ Pediatric Dermatology Unit, Department of Medicine, University of Padova, Padova, Italy.
²² Department of Dermatology and Allergy Biederstein, Faculty of Medicine, Technische Universität München, Munich, Germany.
²³ KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group and MASTeL, University Hospitals Leuven, Leuven, Belgium.
²⁴ Division of Hematology, Istanbul Medical School, University of Istanbul, Istanbul, Turkey.
²⁵ University Hospital and Faculty of Medicine, Brno, Czechia.
²⁶ Faculty of Medicine and Health Sciences, Department of Immunology-Allergology-Rheumatology, University of Antwerp and Antwerp University Hospital, Antwerpen, Belgium.
²⁷ Department of Dermatology and Venereology, University Hospital Graz, Graz, Austria.
²⁸ University Hospital of Leipzig, Leipzig, Germany.
²⁹ Division of Allergy, Department of Dermatology, University of Basel, Basel, Switzerland; Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
³⁰ French Reference Center for Mastocytosis (CEREMAST), Hôpital Necker, Assistance Publique Hôpitaux de Paris, Imagine Institute, University Paris Descartes, Paris, France.
³¹ Laboratory of Hematology, Pitié-Salpêtrière Hospital, Paris, France.
³² Department of Oncology, Haematology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany; Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.
³³ Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: mohamad.jawhar@medma.uni-heidelberg.de.

PMID: 36403897
DOI: 10.1016/j.jaip.2022.10.051

Abstract

Background: Organomegaly, including splenomegaly, hepatomegaly, and/or lymphadenopathy, are important diagnostic and prognostic features in patients with cutaneous mastocytosis (CM) or systemic mastocytosis (SM).

Objectives: To investigate the prevalence and prognostic impact of 1 or more organomegalies on clinical course and survival in patients with CM/SM.

Methods: Therefore, 3155 patients with CM (n = 1002 [32%]) or SM (n = 2153 [68%]) enrolled within the registry of the European Competence Network on Mastocytosis were analyzed.

Results: Overall survival (OS) was adversely affected by the number of organomegalies (OS: #0 vs #1 hazard ratio [HR], 4.9; 95% CI, 3.4-7.1, P < .001; #1 vs #2 HR, 2.1, 95% CI, 1.4-3.1, P < .001; #2 vs #3 HR, 1.7, 95% CI, 1.2-2.5, P = .004). Lymphadenopathy was frequently detected in patients with smoldering SM (SSM, 18 of 60 [30%]) or advanced SM (AdvSM, 137 of 344 [40%]). Its presence confered an inferior outcome in patients with AdvSM compared with patients with AdvSM without lymphadenopathy (median OS, 3.8 vs 2.6 years; HR, 1.6; 95% CI, 1.2-2.2; P = .003). OS was not different between patients having organomegaly with either ISM or SSM (median, 25.5 years vs not reached; P = .435). At time of disease progression, a new occurrence of any organomegaly was observed in 17 of 40 (43%) patients with ISM, 4 of 10 (40%) patients with SSM, and 33 of 86 (38%) patients with AdvSM, respectively.

Conclusions: Organomegalies including lymphadenopathy are often found in SSM and AdvSM. ISM with organomegaly has a similar course and prognosis compared with SSM. The number of organomegalies is adversely associated with OS. A new occurrence of organomegaly in all variants of SM may indicate disease progression.

Keywords: Hepatomegaly; Lymphadenopathy; Mastocytosis; Organomegaly; Splenomegaly; Systemic mastocytosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Disease Progression
Humans
Lymphadenopathy*
Mastocytosis* / diagnosis
Mastocytosis, Cutaneous*
Mastocytosis, Systemic* / diagnosis
Mastocytosis, Systemic* / epidemiology
Prognosis