Haema 2012; 3(3): 266-274
by Panayotis Kaloyannidis1, Panagiotis Tsirigotis2, Ioanna Sakellari1
1Department of Haematology and Bone Marrow Transplantation, Papanikolaou General Hospital, Thessaloniki,
2Second Department of Internal Medicine, Propaedeutic, University of Athens, University General Hospital “Attikon”, Greece
Abstract
The role of allogeneic transplantation (allo-HCT) in Hodgkin’s lymphoma (HL) remains controversial and needs to be further investigated in the era of reduced intensity conditioning regimens (RIC). AlloHCT with the use of myeloablative conditioning was associated with significant non-relapse mortality (NRM). However we should take into account that the vast majority of patients were heavily pre-treated with significant co-morbidities. The indirect evidence of graft versus Hodgkin’s lympho- ma effect was defined by studies which report that the administration of donor lymphocyte infusions (DLIs) is beneficial, even without preceded chemotherapy.τhe rationale of allo-HCT in HL is based on: a)graft versus Hodgkin’s effect, b) the absence of Reed Stenberg in the graft, c) correction of disease related immune-suppression, d) inadequate graft collection for autologous HCT, and e) prevention/cor- rection of therapy-related genetic Along with developments in transplant procedure after 2000, ie the introduction of alloHCT with reduced intensity conditioning (RIC-HCT) which resulted in a significant lower NRM, the role of alloHCT in patients with HL needs to be re-considered. In a EBMT retrospective study, the probabilities of 3-year OS, PFS, and NRM in 285 patients who received various fludarabine-based RIC regimens were 39%, 25%, and 21% respectively. High relapse rate (up to 60%) emerged as the major cause of failure. Similar results were reported in a large prospective phase II co- operative study conducted by EBMT and Spanish group. Four-year PFS was 24% for the whole cohort, while patients transplanted in CR had a better outcome. Predictive negative factors which influence the outcome were: poor performance status, chemo-refractory disease, and a short PFS after autoHCT. The recently published Greek experience, examined the outcome of patients with relapsed disease post autoHCT. Nineteen patients underwent RIC-HCT and the probability of 4-year OS was 55%. Moreover, a prognostic system was proposed based on the presence of 3 factors with a negative impact on OS: a) re- lapse within a year post autoHCT, b) chemorefractory disease at the time of auto HCT, and c) B-symptoms at relapse. Further improvement of the efficacy of alloHCT is needed and future studies should focus on several issues: a) definition of criteria for patient selection, ie patients with low-tumor burden and chemosensitive disease, b) intensification of conditioning regimen without increasing toxicity, c) prophylactic or preemptive DLIs, d) PET-CT scan for early diagnosis of disease progression and treatment with preemptive DLIs e) targeted therapy with brentuximab vedotin, and f) emerging cellular therapies using CTLs with specificity against antigens expressed on the surface of Reed-Sternberg cells. The planned tandem autoHCT followed by RIC-HCT needs further testing, while the optimal RIC condition- ingregimen has not been established so far. Based on current evidence, only patients with chemosensitive relapse after autoHCT should be considered as candidates for alloHCT.