The role of hematopoietic stem cell transplantation for relapsed and refractory <scp>H</scp>odgkin lymphoma
Authors: Joel Collins, Kirk Morris, Mimi Yue, Caroline Mcnamara, Nicholas Weber, Cameron Curley, Glen Kennedy
Journal: American Journal of Hematology (2015)

We read with great interest the article by Kako et al. 1 describing their experience in hematopoietic stem cell transplantation (HSCT) in relapsed and refractory classical Hodgkin Lymphoma (cHL). However, with respect to the 122 allogeneic transplants reported in their series, only gender and performance status, and not conditioning intensity, were significantly associated with overall survival (OS). Our own experience of allogeneic HSCT in cHL albeit in a smaller number of patients is in contrast to these findings. Since 2001 we have performed 21 allogeneic HSCT in patients with multiply relapsed/refractory cHL. Between 2001 and 2008 (early cohort), a non-standardized conditioning approach was used in a total of 11 patients, comprising myeloablative (n = 3), reduced intensity conditioning (RIC; n = 1), and non-myeloablative (n = 7) protocols. From 2009 (late cohort), a standardized RIC approach comprising fludarabine 125 mg/m2 plus melphalan 120 mg/m2 was used in all patients (n = 10). All transplants were T-replete. Brentuximab vedotin was not used in any patient post allogeneic HSCT. Aside from the different conditioning regimens used between the early versus late transplant cohorts (P < 0.0001), no other significant difference was noted between cohorts with respect to patient and/or transplant characteristics, including age (median 25 years; P = 0.72), gender (57% male; P = 0.67), disease stage at allogeneic HSCT (28.5% stage III/IV; P = 0.63), disease status (overall 75% CR/PR; P = 0.58), prior autologous transplant (overall 81%; P = 1.0), prior number of treatment lines (overall 71% > 3 prior lines; P = 1.0), donor source (overall 52% matched unrelated donors; P = 0.15), or stem cell source (overall 90% peripheral blood progenitor cells; P = 0.48). On univariate analysis, the only factor predictive of OS was transplant cohort (Fig. 1), with the late cohort utilizing standardized fludarabine + melphalan RIC associated with a significant improvement in OS (P = 0.004). Although not statistically significant, in comparison to the early cohort, the late (RIC) transplant cohort was also associated with a lower incidence of moderate to severe acute graft versus host disease (GVHD; 20% vs. 45% respectively; P = 0.36), extensive stage chronic GVHD (11% vs. 67% respectively; P = 0.05), and improved 2-year non-relapse mortality (NRM; 10% vs. 45% respectively; P = 0.12). Relapse free survival (RFS) was similar between groups. OS early versus late transplant cohorts. Our experience of improved allogeneic HSCT outcomes in cHL with utilization of RIC is in agreement with larger published series 1-5. In general, RIC approaches appear to offer the best balance between NRM and RFS in allogenic HSCT in relapsed/refractory cHL, with myeloablative conditioning associated with excessive toxicity/NRM and non-myeloablative conditioning with inferior RFS 2, 5. Why conditioning intensity failed to be associated with allogeneic HSCT outcome in the series reported by Kako et al. 1 is unclear. However, we believe that our experience highlights that conditioning intensity is indeed of critical importance to post allogeneic HSCT outcome in relapsed/refractory cHL. Joel Collins,1* Kirk Morris,1 Mimi Yue,1 Caroline Mcnamara,1 Nicholas Weber,1 Cameron Curley,1 and Glen Kennedy1,2 1Cancer Care Services, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia 2School of Medicine, University of Queensland, St Lucia, Queensland, Australia