Outcome of Refractory or Relapsed Patients after Front-Line Treatment for Hodgkin Lymphoma (HL): Experience of a Single Institution
Authors: Fioritoni Francesca , Angrilli Francesco , Falorio Simona , Santarone Stella , Fioritoni Giuseppe 
Published: April 2020

Abstract
Background: Most patients (pts) with HL can be cured today. Nevertheless, 10 to 40% of pts fail to respond to front-line treatment or relapse both early and late. Pts who do not achieve complete remission with conventional treatment or who present early relapse have poor prognosis compared with pts who develop late relapse. The treatment of choice for refractory or early relapsed pts is high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT), while late relapsed pts may be treated with either conventional therapy or HDC plus ASCT. The purpose of this study is to evaluate the results of our experience in the treatment of refractory or relapsed HL pts.
Methods: From January 1999 to December 2007, 179 untreated pts with HL have been admitted in our institution and 176 completed treatment today. Front-line treatment included 4–6 courses of ABVD polychemotherapy in combination with involved field radiotherapy (IFRT) (36 Gy) in clinical stage (CS) I–IIA, and 6 courses of ABVD, COPPEBVCAD (cyclophosphamide, lomustine, vindesine, melphalan, prednison, epidoxorubicin, vincristine, procarbazine, bleomycin, vinblastine) or BEACOPP in CS IIB–IV. Overall, 157 pts (89%) obtained a complete response (CR) and 9 (6%) of them relapsed. In particular, 4 pts relapsed within 12 months after diagnosis of HL, while 5 pts experienced late relapse. The remaining 19 pts (11%), who obtained a minor response or failed to respond, were classified as having a refractory disease after front-line therapy. Twenty-six pts received, as salvage treatment, 3–6 courses of IGEV (iphosphamide, gemcitabine, vinorelbine). The other 2 pts received 6 courses of COPPEBVCAD and 6 courses of ABVD, respectively. Nineteen pts (11 with refractory disease and 8 with relapsed disease) have been submitted also to ASCT with BEAM conditioning regimen. Retrospectively, we evaluated the response rate, overall survival (OS) and disease free survival (DFS) in our 28 refractory-relapsed pts.
Results: 15 pts were male and 13 female (M/F ratio: 1,15); median age was 34 years (range: 16–59). At the time of diagnosis 5 pts presented CS I–IIA and 23 CS IIB–IV. B symptoms and bulky disease were present in 18 (64%) and 15 (54%) pts respectively. Twenty-seven pts completed salvage treatment today. Seventeen pts (63%) obtained a CR, while 10 pts (37%) had progressive disease (PD). In particular, CR and PD in refractory pts were 56% and 44%, in comparison to 78% and 22% in relapsed pts. With a median follow-up of 23 months (range 3–80), OS was 53%. Ten pts dead of progressive HL; another patient dead in CR of BEAM toxicity prior to ASCT. DFS of the CR pts was 85%. Only 2 refractory pts, who obtained a CR after salvage treatment, relapsed after 5 and 23 months respectively.
Conclusion: Our data confirm that HDC plus ASCT is useful both in relapsed and in refractory pts with HL. Nevertheless, nearly half of refractory pts fail to respond to salvage treatment and die of progressive lymphoma. The selection of these latter pts is very difficult today. An advanced disease with a high international prognostic score could be an effective risk indicator at the time of diagnosis. Moreover, an early PET/CT, during salvage treatment, could select the pts who remain unresponsive. Anyway, new treatment modalities are required for these pts.