Hodgkin Lymphoma (HL) in Tunisia Results of a 5 Year Prospective Multicenter Trial in 251 Pts
Authors: Ben Lakhal R. , Hdiji S. , Laatiri M. A , Ladeb S. , Jeddi R. , Aissaoui L. , Ben Amor R. , Msadek F. , Frikha H. , Toumi N. , Daoud J. , Bouaouina N. , Ali Z. Belhadj , Ben Abid H. , Frikha M. , Elloumi M. , Khelif A. , Meddeb B. , Fenaux Pierre 
Published: April 2020

Abstract
Background: HL, independently of socio economic conditions, is often intrinsically more aggressive in developing countries, including in Tunisia (Tunis Med.1999 77:614). We evaluated clinical characteristics and outcome of HL pts included in a prospective multicenter Tunisian adult HL trial.
Methods: Between 2002 and 2006, 251 consecutive eligible pts from 6 Tunisian departments with newly diagnosed HL were enrolled in a prospective trial (MDH 2002). Pts were staged using EORTC prognostic factors in early stages and the international prognostic scoring (IPS) in advanced stages. ABVD was used at 3 cycles for favorable (fav) early stages (G1), 6 cycles for unfavorable (unfav) early stages (G2) and stage IIIA (G3) and 8 cycles for fav advanced stages (IPS &lt;3) (G5). Involved field RT was combined to chemotherapy (CT) for early stage and stage IIIA. Intensive CT (4 escalated BEACOPP + 4 standard BEACOPP) was used for unfav advanced stages (IPS 3 3): (G4). G-CSF was given after each escalated BEACOPP course Refractory and relapsed pts were proposed for intensive CT and autologous SCT. Closing date of the study was Dec 2007
Results: Median age at presentation was 31 years (range 15–70), with 140 M and 111 F. 50% patients had advanced disease (28% with stage IV) and 44% had unfav early stage (G2). 25% pts had Bulky mediastinal disease and 69% had B symptoms. 40% pts were treated in G2, 29% in G4, 17% in G5 and only 9% in G1. Eleven (4.3%) toxic deaths were observed during treatment, including 10 deaths in the 72 pts treated with escalated BEACOPP. Of the remaining pts, 83% had CR and 17% had primary failure at the end of the planned treatment (including 14 % with response &lt;50% and 3 % with response between 50 and 75 %. Only 17 (42%) of the primary failure pts could receive auto SCT (13 pts alive in CR, 2 progressive disease and 2 relapses). The 23 remaining refractory pts had progressive disease and died before SCT (16 pts) or failed to respond to salvage CT before SCT (7pts). Twenty five relapses (12%) were observed with a median time to relapse of 9 months: 9(10%) in G2, 6(8%) in G4 and 10(23%) in G5. Five year OS, EFS, and RFS were respectively 88%, 73% and 88%. In multivariate analysis, the only unfavorable prognostic factors emerging were bulky mediastinal disease for primary failure rate (35% vs 10% p=0.0004, OR=5.3) and for EFS (55% vs 80% p = 0.03, OR = 1.9)and remission status at the end of therapy which influenced EFS (87% vs50% vs5% p=0.0000, OR=21.8) and OS (96% vs62%vs 55% p=0.001, OR=14.6) in pts who achieved CR, had primary failure with &gt;50 % to 75% response and with &lt;50% response, respectively
Conclusions: This study confirms the high incidence of aggressive forms of HD in Tunisia, therefore frequently requiring intensive treatment, sometimes difficult to apply in pts with relatively low socio economic condition Apart from escalated BEACOPP (which resulted in high toxicity that will have in the future to be better prevented), treatments could however generally be administered completely, which possibly contributed to the relatively few relapses. Bulky mediastinal disease and absence of CR at the end of treatment were, as in other countries, major issues requiring treatment intensification