LAUSR

A majority of patients with classical Hodgkin lymphoma (cHL) will achieve remission with frontline treatment and have long-term disease control. However, approximately 10– 15% of early-stage (favourable) and 15–30% of advancedstage cHL will relapse after frontline treatment. For patients with relapsed/refractory cHL, treatment with salvage chemotherapy followed by autologous haematopoietic cell transplantation (auto-HCT) is potentially curative. Of those who undergo auto-HCT, c. 50% will relapse and portend a very poor outcome, with a 5-year overall survival (OS) of c. 30%. Allogeneic HCT (allo-HCT) is a potentially curative option for these patients (who relapse following autoHCT) and is an important therapeutic strategy in the treatment armamentarium for patients with cHL. One of the important factors that determine the long-term outcomes following allo-HCT is the type of conditioning regimen/conditioning intensity. While myeloablative conditioning (MAC) regimens offer the potential for improved progression-free survival (PFS), they are associated with higher rates of nonrelapse mortality (NRM) in the majority of the previously published studies without an OS advantage. More importantly, there was no superiority of MAC over reducedintensity conditioning (RIC) or non-myeloablative conditioning (NMA). Although the RIC approach has been studied in relapsed/refractory cHL, there is a paucity of data comparing various RIC regimens for patients with cHL undergoing allo-HCT, underscoring the importance of the study by Dr Ahmed and colleagues. In the current study, Ahmed et al. report the outcomes of the three most commonly used RIC regimens in patients with cHL undergoing allo-HCT using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. The three RIC regimens examined were fludarabine/intravenous busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) and fludarabine/cyclophosphamide (Flu/Cy). A total of 492 adult patients with cHL, who underwent a first allo-HCT using either a matched sibling or matched unrelated donor between 2008 and 2016, were included in the study. The most commonly used RIC regimen was Flu/Mel (n = 318) followed by Flu/Bu (n = 102) and Flu/Cy (n = 72). Careful statistical adjustments were made to account for the differences in the patient population that might be expected to affect progression/relapse, NRM, PFS and OS. The cumulative incidence of NRM at 1 year was significantly lower in Flu/Cy cohort (3%) relative to Flu/Bu (10%) and Flu/Mel140 (10%); however, after adjusting for patient age and donor type, there was no significant difference between the three groups. The probability of relapse/ progression at 4 years was significantly higher in Flu/Cy cohort (65%) relative to Flu/Bu (57%) and Flu/Mel140 (47%); however, after adjusting for remission status at alloHCT, there was no significant difference between the three groups. The probability of PFS and OS at 4 years was not significantly different between the three groups. Although, on OS modelling relative to Flu/Bu, Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT. In summary, the authors conclude that the choice of RIC regimen does not impact the risk of NRM, relapse, PFS or graft-versus-host disease (GVHD) in patients with cHL undergoing allo-HCT. The one exception being Flu/Cy, which was associated with worse OS. Ahmed et al. report superior PFS and OS at 4 years for patients with cHL undergoing RIC allo-HCT compared to the previously published registry studies. This is an important finding. This improvement in survival could be *Correspondence: Narendranath Epperla, Division of Hematology, Wexner Medical Center, Ohio State University, Columbus, OH, USA. E-mail: [email protected] commentary