Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies
Authors: Hernández-Molina Gabriela , Kostov Belchin , Brito-Zerón Pilar , Vissink Arjan , Mandl Thomas , Hinrichs Anneline C , Quartuccio Luca , Baldini Chiara , Seror Raphaele , Szántó Antonia , Isenberg David , Gerli Roberto , Nordmark Gunnel , Rasmussen Astrid , Solans-Laque Roser , Hofauer Benedikt , Sène Damien , Pasoto Sandra G , Rischmueller Maureen , Praprotnik Sonja , Gheita Tamer A , Danda Debashish , Armağan Berkan , Suzuki Yasunori , Valim Valeria , Devauchelle-Pensec Valerie , Retamozo Soledad , Kvarnstrom Marika , Sebastian Agata , Atzeni Fabiola , Giacomelli Roberto , Carsons Steven E , Kwok Seung-Ki , Nakamura Hideki , Fernandes Moça Trevisani Virginia , Flores-Chávez Alejandra , Mariette Xavier , Ramos-Casals Manuel ,   the Sjögren Big Data Consortium, Brito-Zerón P , Flores-Chávez A , Ramos-Casals M , Horvath I F , Szántó A , Tarr T , Ng F , Rasmussen A , Farris D A , Dong X , Yan Z , Li X , Xu B , Baldini C , Bombardieri S , Mandl T , Olsson P , Priori R , Giardina F , Izzo R , Seror R , Mariette X , Gottenberg J E , Kruize A A , Hinrichs A , Bootsma H , Vissink A , Danda D , Sandhya P , Hernandez-Molina G , Sánchez-Guerrero J , Armagan B , Kilic L , Kalyoncu U , Quartuccio L , Gandolfo S , De Vita S , Praprotnik S , Sebastian A , Wiland P , Gerli R , Bartoloni E , Kwok S-K , Park S-H , Kvarnstrom M , Wahren-Herlenius M , Rischmueller M , Downie-Doyle S , Solans-Laque R , Sene D , Pasoto S G , Suzuki Y , Kawano M , Isenberg D A , Nordmark G , Valim V , Nakamura H , Shimizu T , Nishihata S -Y , Nakamura T , Takagi Y , Fernandes Moça Trevisani V , Retamozo S , Hofauer B , Knopf A , Fraile G , Giacomelli R , Devauchelle-Pensec , V , Saraux A , Bombardieri M , Astorri E , Atzeni F , Hammenfors D , Brun J G , Carsons S E , Maure Noia B , Argibay Filgueira A B , Gheita T A , Sánchez Berná I , López Dupla M , Alberto Rojas R , Febrer Nafria A M , Morel J , Fonseca Aizpuru E , Santos Seoane S , Brito-Zerón P , Morcillo C , Melchor Díaz S , Carreira P , Vollenveider C , Vázquez M , Ericka Díaz Cuiza P , Herrera B E , Andrea Consani S , Comotto A , de Miguel Campo B , Kostov B , Sisó-Almirall A , Kostov B , Acar-Denizli N 
Published: April 2022

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%.