Haema 2017; 8(1): 83-94
by Ioanna Sakellari
Haematology Department – Bone Marrow Transplantation Unit, G. Papanicolaou, Hospital, Thessaloniki, Greece
Abstract
Autologous hematopoietic cell transplantation (AutoHCT) is established as a standard of care for chemosensitive Non-Hodgkin Lymphoma (NHL) patients who experience progression or relapse of disease. The poor outcome of conventional salvage therapy has led to the increasing application of high dose therapy followed by autoHCT, as dose escalation may result in large scale of tumor cell kill and theoretically, in durable remission or cure for chemosensitive disease. High-risk aggressive B-cell lymphoma, mantle cell lymphoma (MCL), relapsed or refractory B-cell lymphoma and peripheral T-cell lymphoma (PTCL) have poor overall survival (OS) with conventional chemotherapy and are candidates for high-dose chemotherapy followed by autoHCT or alloHCT. Pioneering works of the 90s defined the role of AHCT and two decades afterwards a significant body of data has now accumulated.The landmark study for the pre-Rituximab era demonstrated the superiority of AHCT over salvage regimen in relapsed NHL and subsequently AHCT became a standard approach. In the rituximab era, the randomized study to 3 courses of either R-DHAP or R-ICE with comparable results confirmed the PARMA study, reporting a 3-year PFS of 53% in chemosensitive patients after BEAM and AHCT. Hence, transplant-eligible patients should undergo high dose therapy (HDT)/autoHCT in the first relapse. Various clinical factors, such as age-adjusted IPI, increased LDH at diagnosis, older age and poor performance status predict poor outcomes. Primary refractory disease, refractory relapse and disease relapse within 12 months of the diagnosis are important predictors of poor outcomes. In addition to the clinical factors, retrospective studies have shown better outcomes in patients with a negative PET scan before autoHCT. Although a positive pre-autoΗCT PET scan may be prognostic, whether a positive PET should change the management remains unanswered. Thus, autoHCT in DLBCL should be considered in select transplant-eligible primary refractory patients who have chemosensitive disease to salvage therapy. MCL, approximately 6% of NHL, is incurable with conventional chemotherapy and a median OS of 3-6 years with conventional tional chemotherapy. Several studies, predominantly non-randomized trials and retrospective studies, have evaluated the role of up-front autoHCT in young patients with symptomatic MCL following various induction regimens. This study indicates that up-front HDT/autoHCT may improve outcomes in PTCL, compared with autoHCT in the relapse setting. However, HDT /autoHCT has an important role in the management of patients with relapsed PTCL. Memorial Sloan-Kettering Cancer Center compared autoHCT for relapsed or refractory PTCL with DLBCL and the results were similar. Although the outcome of relapsed PTCL is poor, chemosensitive patients may benefit from HDT/autoΗCT. Patients with DLBCL who fail multiple chemotherapies or autoHCT have poor outcomes, with a median OS of approximately 10 months in the rituximab era. These patients may be candidates for alloHCT. Conventional alloHCT has been investigated in clinical studies for refractory lymphomas due to the anticipated graft vs lymphoma effect but treatment related mortality (TRM) was high. TRM has led to the utilization of reduced intensity conditioning (RIC-HCT). Non-myeloablative regimens followed by alloHCT are being actively applied in the last decade in patients with NHL as they provide encouraging results with low TRM. The main issue of the above regimens is the high relapse rate. In a retrospective study comparing autoHCT and alloHCT in MCL, alloHCT resulted in similar PFS at 5 years. AlloHCT may be useful in multiply relapsed PTCL or after failure of autoΗCT. In a CIBMTR study, outcomes of patients with PTCL who underwent autoΗCT were compared with those who underwent alloΗCT. AutoHCT, compared with myeloablative and RIC-HCT, showed similar PFS and lower OS at 3 years. These studies suggest that RIC alloHCT with graft-versus-lymphoma activity may result in long-term disease control in PTCL. To sum up, there is an urgent need to adapt personalized therapy guided by validated prognostic tools according to the clinical and biological heterogeneity of the aggressive lymphomas. Some patients could benefit from targeted approaches, such as the new, molecular-directed, immunomodulating compounds with high efficacy and a good safety profile. The role of transplantation and modern therapeutic options will be redefined based on the biological insights into the molecular pathogenesis and the therapeutic scenario for has been shown to be favourable. Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor.