RIC Allogeneic Transplantation Improves the Overall and Progression- Free Survival of Hodgkin Lymphoma Patients Relapsing after Autologous Transplantation: A GITMO Retrospective Study Based on Time of HLATyping and Donor Availability

Background: Hodgkin Lymphoma (HL) patients (pts) relapsing after autologous transplantation (auto-SCT) have a very poor outcome with no chemotherapy options able to obtain a long term disease control. Allogeneic stem cell transplantation (allo-SCT) employing reduced intensity conditioning (RIC) is increasingly used in lymphomas, but the number of studies in HL is quite limited, some groups reported conflicting results, and thus no clear evidence exists on its role as an effective salvage option in the clinical setting.

Aims: We investigated the role of RIC allo-SCT in HL pts relapsing or progressing after auto-SCT (primary refractory patients were not included). Our study was structured similarly to an intent to treat analysis, and thus was based on the commitment of the attending physician to perform an allo-SCT. Only those pts undergoing a HLA-typing immediately after the failure of auto-SCT were included. The cohort of pts having a donor (donor group) was compared with the one not having a suitable donor (no donor group).

Patients and Methods: 132 pts were retrospectively evaluated, for all of them a search for a sibling or matched unrelated donor (MUD) was started at the time of relapse/progression after auto-SCT. Seventy-five pts found a donor and 68 (90%) underwent an allo-SCT: 36 identical siblings (52%), 23 MUD (33%), 6 haploidentical family donors (9%). Thiotepa, cyclophosphamide and fludarabine containing regimens were used in all pts; GVHD prophylaxis was based on MTX and cyclosporine except for haploidentical-SCT. Seven pts having a donor did not receive allo-SCT for progressive disease. Pts not having a donor (n= 57) received chemo- and/or radiotherapy according to the standard policy of each center. The two cohorts of patients were well balanced in terms of clinical features, in particular the number of patients relapsing/progressing within 6 months from auto-SCT was similar.

Results: The patient median age was 30 years (17–62). The median followup was 24 months. For all pts, the median overall (OS) and progression free survival (PFS) were 31 and 15 months, respectively. The 2-year OS and PFS were 56% and 29% respectively. The cumulative transplant-related mortality was 12% for the donor group. The 2-y OS and PFS were significantly better in the donor compared to the no donor group (OS 70% vs 38.8%, p 0.001, long rank test; PFS 42% vs 10%, p 0.03, long rank test). In multivariate analysis having a donor was statistically significant for OS and PFS. When we considered only the pts actually allografted, again the 2-years OS and PFS were significantly better compared to the no allo-group (OS 77% vs 35% and PFS 47% vs 9.3%). Acute GVHD grade II-IV occured in 17 pts (25)% and chronic GVHD in 27 pts ( 40%). In multivariate analysis, being in complete remission before allo-SCT significantly improved OS and PFS.

Conclusions: This is the largest study comparing RIC allo-SCT vs conventional treatment in HL patients failing an auto-SCT. Allo-SCT is a feasible option and prolongs OS and PFS. As expected, the attainment of complete remission before allo-SCT improves the outcome.