haematologica reports 2006; 2(issue 7):May 2006 94 [haematologica reports] 2006;2(7):94-95 J.G. GRIBBEN Bartholomew’s Hospital, Barts and The London School of Medicine, London, UK Transplantation for low-grade lymphoma T he low grade lymphomas remains incurable and notwithstanding the excellent remission rates now achieved with combination chemotherapy with mon- oclonal antibodies, the vast majority of patients are destined to relapse after pri- mary treatment. The management of relapsed patients is then dependent upon a number of factors, most importantly age, performance status, previous therapy administered, the response and duration of response to such therapy, and time from last therapy. Although prior therapy and response to such therapy are important fac- tors in determining next therapy, it is often difficult to determine their importance from published studies. Furthermore, the goal of therapy, whether palliative or aggressive, must also be weighed into the decision when deciding on the next line of treatment. With many potential treatments available, the sequence of treatments and the timing of procedures such as stem cell transplantation remain controversial and have been the focus of previous and ongo- ing clinical trials. In follicular lymphoma, high dose thera- py followed by autologous stem cell trans- plantation (SCT) is associated with very high response rates, but may also not be curative in the majority of cases, as these initial remissions are followed by a seem- ingly relentless pattern of relapse. In a number of phase II studies, five year pro- gression free and overall survival are in the order of 40-60% and 50-80% respective- ly. 1-3 with good outcome in patients treat- ed by SCT following sequential high dose therapy. 4 These findings suggest that high dose therapy and autologous stem cell transplant may improve outcome compared to conventional chemotherapies, a finding supported by the findings of the CUP study. 5 There have been concerns about the late toxicities associated with high dose thera- py, particularly with the use of total body irradiation containing regmins, with thera- py related MDS/AML causing specific con- cern with rates 5 years post autograft ris- ing to 12%. 1,6 Several studies have retro- spectively compared outcome following allogeneic versus autologous transplanta- tion in patients with indolent lymphoma. 7-9 In these studies patients undergoing allo- geneic SCT were more likely to have high risk features prior to transplant compared those undergoing autologous transplanta- tion. As would be expected treatment relat- ed mortality following allogeneic SCT was significantly higher compared with autolo- gous SCT however a reduced relapse rate resulted in no significant difference in over- all survival despite the poor risk character- istics of the patients undergoing allogene- ic transplantation. Although the median age at presentation of CLL patients is 65 years, 40% are younger than age 60, and 12% are younger than age 50 at presentation. In addition, a number of clinical and biological features can be used to identify high-risk patients before they become refractory to chemotherapy. Younger patients with poor risk CLL are being offered therapies such as SCT to attempt to prolong survival and potentially cure their disease. High-dose therapy and autologous hematopoietic SCT are feasible in the many younger patients with poor-risk CLL, but the utility of this approach remains unproven, since no stud- ies to date have compared the role of stan- dard chemotherapy with SCT in CLL. In a study comparing the outcome of autolo- gous versus allogeneic SCT, there was no difference in survival between these two modalities. 10 Given the older age group of the majori- ty of patients with low grade lymphoma, it seems most reasonable to consider non- myeloablative conditioning regimen trans- plants for patients in whom allogeneic SCT is being considered. This approach appears capable of harnessing the graft versus lym- phoma effect cells whilst keeping trans- plant related mortality low. A number of studies have demonstrated the graft versus lymphoma effect following reduced inten- sity conditioning regimens. 11-14