Allogeneic Stem-Cell Transplantation in Hodgkin Lymphoma; A More Favorable Outcome in Patients with Chemo-Sensitive Disease and with Treosulfan-Based Conditioning

Allogeneic stem cell transplantation (alloSCT) is a potentially curative therapy for patients (pts) with Hodgkin lymphoma (HL) relapsing after autologous SCT (autoSCT). Myeloablative conditioning is associated with high non-relapse mortality (NRM) in this setting and reduced-intensity conditioning is often the preferred option. Historically, we have used the combination of fludarabine and intravenous busulfan or melphalan (FB/FM). Over the last 2 years we used the combination of fludarabine and treosulfan (FT). Treosulfan is a pro-drug of a bi-functional alkylating agent with intensive myelosuppressive as well as immunosuppressive properties and a relatively favorable toxicity profile. It was predominantly explored in pts with myeloid malignancies and there is only limited data on the expected outcomes of this regimen in pts with lymphoid malignancies. We analyzed the outcomes of 27 pts with HL, given alloSCT, after failure of a previous autoSCT. The median age was 30 years (range, 20-62), 18 male, 9 female. The donor was an HLA matched sibling (n=12), matched unrelated (n=14) and umbilical cord blood (n=1). This was a relatively high-risk patient group with 18 pts having chemo-refractory disease at SCT and only 9 responded to the last course of therapy. Nineteen pts were given FB/FM conditioning and the most recent 8 pts were given FT with a total treosulfan of 30-32 g/m2. The median follow up of surviving pts is 12 months (range, 4-85 months). Eight pts are currently alive and progression-free, 8 pts had NRM and 11 relapsed. All relapses occurred within the first year after SCT. The estimated 2-year cumulative incidence of NRM and relapse was 30% (95%CI 17-53%) and 45% (95%CI 29-70%), respectively. The estimated 2-year overall survival (OS) rate is 34% (95% CI 14-55%) and the 2-year progression-free survival (PFS) is 25% (95% CI 7-43%). The 2-year PFS for pts with chemo-sensitive and chemo-refractory disease was 53% (95%CI, 19-87) and 9% (95%CI, 0-25), respectively (p=0.01). Pts given FB/FM conditioning had a 2-year PFS of 16% (95%CI, 0-32) compared with pts conditioned with FT who had a PFS of 63% (95%CI, 29-96, p=0.18). In multivariant analysis, chemo-refractory disease was associated with inferior PFS, HR 4.2 (1.3-13.5), p=0.02. There was a trend for better PFS after FT conditioning, after adjusting for other variables, HR 0.3 (0.1-1.2), p=0.08. Age, gender and donor type were not significant predicting factors. In conclusion, alloSCT can salvage a subset of pts with HL relapsing after autoSCT, but has a limited role in pts with chemo-refractory disease at SCT. Treosulfan-based conditioning is promising in this entity, and merits further study in larger comparative studies.