High-Dose Sequential Chemotherapy (HDS) Followed by Autologous Stem Cell Transplantation (ASCT) in Relapsing/Refractory Hodgkin Lymphoma (HL): Long-Term Results.
Authors: Gallamini Andrea , Castellino Claudia , Viviani Simonetta , Rossi Andrea , Billio Atto , Mistretta Alessandro , Sorio Marco , Gueli Angela , Rambaldi Alessandro , Cortelazzo Sergio , Patti Caterina , Benedetti Fabio , Torchio PierFederico , Gianni Alessandro M. , Tarella Corrado 
Published: October 2019

Abstract
From January 1986, 205 consecutive HL patients (p) were enrolled in a multicenter observational study to explore the role of HDS followed by ASCT in refractory or relapsed HL (refHL/relHL).
Patients and methods: The mean age was 32.4 (11–61), the male/female ratio was 104/101. Limited (I–II) or advanced stage (III–IV) was present in 87 and 118 p, respectively. The first-line chemotherapy was ABVD (93 p), hybrid MOPP/ABVD (8p), alternating MOPP/ABVD (47p), other (37p), two or more chemotherapy lines (20 p). Radiotherapy (involved or extended field) was given in 95 p. 58 p had refHL, and 147 relHL: 130/147 were in first and 17/147 were in 2nd or more than 2nd relapse, respectively. The first relapse occurred before-(e-Rel) or later than (l-Rel) 12 months in 31 and 99 p, respectively. The standard HDS included DHAP (optional), Cyclophosphamide 7 gr./m2, Methotrexate 8 gr/m2, Vincristine 1.4 mg/m2, Etoposide 2 gr/m2. In 58/205 p. Metotrexate was substituted with ARA-C, 4gr/m2 per 4 days. The conditioning regimen was BEAM (65), Mitoxantrone 60 mg/m2 and Melphalan 140 mg/m2 (100) or TBI (12.5 Gy)+ Melphalan 140 mg/m2 (20) or other (9). The graft consisted in peripheral Blood Stem Cells (PBSC) or Bone Marrow (BM) or both in 160, 20 and 14 patients.
Results: The International Prognostic Score at relapse (IPS-r) was 0–4 in 185 p, 5–7 in 6 p and unknown in 14. ASCT was done in 194 p; it could not be done for PBSC harvest failure in 3 or for disease progression in 8. The mean value of CD 34+ cells reinfused (available in 153/194 p) was 6.4 x106/kg for PBCS and 6.3 x 106/Kg for BM grafts. After a median follow-up of 54.4 months (2–252) 117 p were alive and 88 had died. The causes of death were disease (71), toxicity (7) and secondary neoplasm (10). Second tumours were MDS (4), Acute leukaemia (1), non-Hodgkin lymphoma (1), adenocarcinoma (4). The 5-year OS and failure free survival in an intention-to-treat basis were 59.8% and 46.4%, respectively. The 5-y OS and 5-y FFS for refHL was 51.3%. and 41.3%; for relHL 66.6% and 51.4% (p<0.05 and p>0.05); for e-Rel 73.3% and 56.0%; for l-Rel 63.2% and 52.1% (no significant difference: p>0.05 and p>0.05). In univariate analysis the factors correlated to OS were status of disease at transplant (p<0.01), status of disease at program onset (p<0.05), treatment response (RC vs. non-RC) (p< 0.01), high vs. normal LDH (p<0.01), PS (0–2 vs.>2) (p<0.05), secondary MDS (p<0.05). IPS-r was not significant. In multivariate analysis the significant factors were treatment response (HR 0.1), secondary MDS (HR 4.9) and status of disease at transplant (HR 3.4). The treatment related mortality (TRM) was 7.8% (16/205). The 5-year cumulative risk of MDS/Acute leukaemia ad solid tumour was 5.0% and 3.0%.
Conclusions HDS followed by ASCT is an efficacious salvage treatment for relapsing/refractory HL. The feasibility is proven, and the cumulative incidence of 2ary MDS/AL is in the range of the reported literature.