Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Gabriela Hernández-Molina; Belchin Kostov; Pilar Brito-Zerón; Arjan Vissink; Thomas Mandl; Anneline C Hinrichs; Luca Quartuccio; Chiara Baldini; Raphaele Seror; Antonia Szántó; David Isenberg; Roberto Gerli; Gunnel Nordmark; Astrid Rasmussen; Roser Solans-Laque; Benedikt Hofauer; Damien Sène; Sandra G Pasoto; Maureen Rischmueller; Sonja Praprotnik; Tamer A Gheita; Debashish Danda; Berkan Armağan; Yasunori Suzuki; Valeria Valim; Valerie Devauchelle-Pensec; Soledad Retamozo; Marika Kvarnstrom; Agata Sebastian; Fabiola Atzeni; Roberto Giacomelli; Steven E Carsons; Seung-Ki Kwok; Hideki Nakamura; Virginia Fernandes Moça Trevisani; Alejandra Flores-Chávez; Xavier Mariette; Manuel Ramos-Casals; Sjögren Big Data Consortium

doi:10.1093/rheumatology/keac205

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Rheumatology (Oxford). 2022 Dec 23;62(1):243-255. doi: 10.1093/rheumatology/keac205.

Authors

Gabriela Hernández-Molina¹, Belchin Kostov^{2

3}, Pilar Brito-Zerón⁴, Arjan Vissink⁵, Thomas Mandl⁶, Anneline C Hinrichs⁷, Luca Quartuccio⁸, Chiara Baldini⁹, Raphaele Seror¹⁰, Antonia Szántó¹¹, David Isenberg¹², Roberto Gerli¹³, Gunnel Nordmark¹⁴, Astrid Rasmussen¹⁵, Roser Solans-Laque¹⁶, Benedikt Hofauer¹⁷, Damien Sène¹⁸, Sandra G Pasoto¹⁹, Maureen Rischmueller²⁰, Sonja Praprotnik²¹, Tamer A Gheita²², Debashish Danda²³, Berkan Armağan²⁴, Yasunori Suzuki²⁵, Valeria Valim²⁶, Valerie Devauchelle-Pensec²⁷, Soledad Retamozo^{28

29

30}, Marika Kvarnstrom^{31

32}, Agata Sebastian³³, Fabiola Atzeni³⁴, Roberto Giacomelli³⁵, Steven E Carsons³⁶, Seung-Ki Kwok³⁷, Hideki Nakamura³⁸, Virginia Fernandes Moça Trevisani³⁹, Alejandra Flores-Chávez^{40

41}, Xavier Mariette¹⁰, Manuel Ramos-Casals^{41

42}; Sjögren Big Data Consortium

Collaborators

Sjögren Big Data Consortium:
P Brito-Zerón, A Flores-Chávez, M Ramos-Casals, I F Horvath, A Szántó, T Tarr, F Ng, A Rasmussen, D A Farris, X Dong, Z Yan, X Li, B Xu, C Baldini, S Bombardieri, T Mandl, P Olsson, R Priori, F Giardina, R Izzo, R Seror, X Mariette, J E Gottenberg, A A Kruize, A Hinrichs, H Bootsma, A Vissink, D Danda, P Sandhya, G Hernandez-Molina, J Sánchez-Guerrero, B Armagan, L Kilic, U Kalyoncu, L Quartuccio, S Gandolfo, S De Vita, S Praprotnik, A Sebastian, P Wiland, R Gerli, E Bartoloni, S-K Kwok, S-H Park, M Kvarnstrom, M Wahren-Herlenius, M Rischmueller, S Downie-Doyle, R Solans-Laque, D Sene, S G Pasoto, Y Suzuki, M Kawano, D A Isenberg, G Nordmark, V Valim, H Nakamura, T Shimizu, S-Y Nishihata, T Nakamura, Y Takagi, V Fernandes Moça Trevisani, S Retamozo, B Hofauer, A Knopf, G Fraile, R Giacomelli, V Devauchelle-Pensec, A Saraux, M Bombardieri, E Astorri, F Atzeni, D Hammenfors, J G Brun, S E Carsons, B Maure Noia, A B Argibay Filgueira, T A Gheita, I Sánchez Berná, M López Dupla, R Alberto Rojas, A M Febrer Nafria, J Morel, E Fonseca Aizpuru, S Santos Seoane, P Brito-Zerón, C Morcillo, S Melchor Díaz, P Carreira, C Vollenveider, M Vázquez, P Ericka Díaz Cuiza, B E Herrera, S Andrea Consani, A Comotto, B de Miguel Campo, B Kostov, A Sisó-Almirall, B Kostov, N Acar-Denizli

Affiliations

¹ Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
² Primary Healthcare Transversal Research Group, IDIBAPS.
³ Department of Statistics and Operations Research, Universitat Politècnica de Catalunya (UPC).
⁴ Department of Medicine, Autoimmune Diseases Unit, Hospital CIMA- Sanitas, Barcelona, Spain.
⁵ Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁶ Department of Clinical Sciences Malmö, Division of Rheumatology, Lund University, Malmö, Sweden.
⁷ Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁸ Clinic of Rheumatology, Department of Medicine (DAME), University of Udine, ASU FC, Udine.
⁹ Rheumatology Unit, University of Pisa, Pisa, Italy.
¹⁰ Rheumatology Department, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris-Sud - Hôpital Bicêtre, Paris-Saclay University, INSERM UMR1184: Centre for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.
¹¹ Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
¹² Centre for Rheumatology, Division of Medicine, University College London, London, UK.
¹³ Rheumatology Unit, Department of Medicine & Surgery, University of Perugia, Perugia, Italy.
¹⁴ Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹⁵ Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
¹⁶ Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
¹⁷ Otorhinolaryngology/Head and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich,Germany.
¹⁸ Université de Paris, Departement of Internal Medicine, Hôpital Lariboisière, Assistance Publique- Hôpitaux de Paris, Paris, France.
¹⁹ Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
²⁰ Department of Rheumatology, The Queen Elizabeth Hospital, Discipline of Medicine, University of Adelaide, Adelaide, Australia.
²¹ Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia.
²² Rheumatology Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt.
²³ Department of Clinical Immunology & Rheumatology, Christian Medical College & Hospital, Vellore, India.
²⁴ Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
²⁵ Division of Rheumatology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
²⁶ Department of Medicine, Federal University of Espírito Santo, Vitória, Brazil.
²⁷ Rheumatology Department, Brest University Hospital, Brest, France.
²⁸ Rheumatology Department, Hospital Universitari Parc Taulí, Sabadell, Barcelona, Spain.
²⁹ Instituto Modelo de Cardiología Privado SRL, Córdoba, Argentina.
³⁰ Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, Argentina.
³¹ Division of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital.
³² Academic Specialist Center, Center for Rheumatology, Stockholm Health Services, Stockholm, Sweden.
³³ Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland.
³⁴ IRCCS Galeazzi Orthopaedic Institute, Milan and Rheumatology Unit, University of Messina, Messina.
³⁵ Department of Clinical Immunology and Rheumatology, School of Medicine, University of Rome 'Campus Biomedico', Rome, Italy.
³⁶ Division of Rheumatology, Allergy and Immunology, NYU Long Island School of Medicine, Mineola, NY, USA.
³⁷ Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
³⁸ Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
³⁹ Federal University of São Paulo, Sao Paulo, Brazil.
⁴⁰ CONACYT, Mexico City, Mexico.
⁴¹ Department of Diseases, ICMiD.
⁴² Department of Medicine, University of Barcelona, Hospital Clinic, Barcelona, Spain.

PMID: 35385104
DOI: 10.1093/rheumatology/keac205

Abstract

Objective: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes.

Methods: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified.

Results: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL).

Conclusion: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.

Keywords: MALT; SS; haematological malignancy; lymphoma; lymphoproliferative disease.

MeSH terms

Female
Hematologic Neoplasms*
Humans
Leukemia, Lymphocytic, Chronic, B-Cell* / epidemiology
Lymphoma, B-Cell, Marginal Zone*
Lymphoma, Follicular* / pathology
Lymphoma, Large B-Cell, Diffuse*
Middle Aged
Retrospective Studies
World Health Organization

Supplementary concepts

Familial primary gastric lymphoma