Manuel Gotti1, Roberta Sciarra1, Alessandro Pulsoni2, Francesco Merli3, Chiara Rusconi4, Barbara Botto5, Alessandro Re6, Andrea Rossi7, Luigi Rigacci8, Alberto Fabbri9, Marina Liberati10, Michele Merli11, Luca Nassi12, Carmelo Carlo Stella13, Maurizio Bonfichi1, Valentina Zoboli1, Germana Tartaglia2, Isabel Alvarez3, Erika Meli4, Maura Nicolosi5, Daniela Dalceggio6, Silvia Ferrari7, Benedetta Puccini8, Emanuele Cencini9, Viviana Apolloni10, Andrea Ferrario11, Clara Deambrogi12, Francesca Ricci13, Weisman Avital1, Virginia Ferretti1, Luca Arcaini1
1 Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 2 Department of Cellular Biotechnologies and Hematology, ““La Sapienza”“ University, Roma, Italy, 3 Hematology Unit, AUSL-IRCCS of Reggio Emilia, Italy, 4 Division of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, 5 SC Ematologia, Azienda Ospedaliera Citta‘ della Salute e della Scienza, Torino, Italy, 6 Department of Hematology, Spedali Civili, Brescia, Italy, 7 Department of Hematology, Ospedali Riuniti, Bergamo, Italy, 8 Department of Haematology, “Careggi” Hospital, Firenze, Italy, 9 Azienda Ospedaliera Universitaria Senese, U.O.C. Ematologia, Siena, Italy, 10 Onco-Hematology Departmant, S. Maria Hospital, Terni, Italy, 11 Division of Hematology, University Hospital “Ospedale di Circolo e Fondazione Macchi”, ASST Sette Laghi, University of Insubria, Varese, Italy, 12 SCDU Ematologia, AOU Maggiore della Carità, Novara, 13 Department of Hematology & Oncology, Humanitas Cancer Center, Humanitas Clinical & Research Center, Milan, Italy
Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) is a rare entity representing 5% of HL. ESMO recommends involved-field radiotherapy (IFRT) for stage IA and chemotherapy for other stages, but there is no consensus on whether cHL-directed regimens, such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), or B-cell lymphoma-directed agents (rituximab-R) should be used.
The aim of our study was to collect a large series of NLPHL patients (pts) in order to identify prognostic factors and to evaluate the impact of different therapeutic approaches.
We retrospectively collected data on 222 pts diagnosed with NLPHL in 13 Italian centers between 2000 and 2018 (64 stage I, 99 II, 42 III, 17 IV). Median age at diagnosis was 43, male:female ratio was 2.4. Twenty-one pts had spleen involvement, 19 had B symptoms, 23 had extranodal disease, 13 had bulky disease (> 7 cm), and 3 had bone marrow involvement.
Stage I pts were treated with: 22 IFRT, 28 ABVD ± IFRT, 7 R-ABVD ± IFRT, 1 R-CHOP+IFRT, 2 R+IFRT, 1 R alone; 3 pts did not recive any therapy. Patients with stages other than I were treated with: 57 ABVD ± IFRT (37 II; 15 III; 5 IV), 46 R-ABVD ± RT (30 II; 11 III; 5 IV), 32 R-CHOP ± IFRT (13 II, 13 III, 6 IV), 4 observation, 10 IFRT, 5 R ± IFRT, 4 other. Thirty pts relapsed as NLPHL and 5 pts transformed into NHL at a median of 19.9 months. We registered 7 deaths: one for disease progression, 2 for therapy-related toxicities, 4 not related to lymphoma.
Median follow-up was 78.1 months (range 1–367). 5yr-OS was 96.9% and 5yr-EFS for all stages was 85.7% (I 94.8%, II 88.9%, III 73.1%, IV 63.5%; p < 0.001).
For pts with stage II-IV, ORR was 96.4% when treated with ABVD and 100% with both R-ABVD and R-CHOP; 5-yrs EFS was 73.2% with ABVD ± IFRT, 88.4% with R-ABVD and 85% with R-CHOP (p = 0.548). In univariate analysis spleen involvement, bulky disease, involvement of > 3 nodal areas, elevated lactate-dehydrogenase and/or β2-microglobulin, and sub-diaphragmatic involvement resulted statistically related to a short EFS. Spleen involvement, bulky disease and involvement of >3 nodal areas retained a statistically significant prognostic role also in a multivariate analysis.
Our study highlights a good outcome for limited stage and a negative prognostic role of spleen involvement, bulky disease and >3 nodal areas. With regard to therapy, our data show a greater efficacy of immunochemoterapy in comparison to only ABVD but statistical significance in terms of EFS has not been achieved.