High-Dose Therapy and Autologous Stem Cell Transplantation for Extra-Nodal NK/T Lymphoma in Western Patients; A Study From the European Group for Blood and Marrow Transplantation (EBMT).

Abstract 3148

Extra-nodal NK/T lymphoma (ENKTL) is an aggressive malignancy with a unique geographical distribution; rare in Western countries and more frequently encountered in East Asia. ENKTL is invariably associated with Epstein Barr Virus (EBV) and characteristically involves the nasal cavity, though extra-nasal disease is not uncommon. For a majority of patients, treatment outcomes are unsatisfactory. For localised disease, radiotherapy is effective although up to 50% of patients will relapse, usually within a year of first-line therapy. The outcome of advanced stage and relapsed/refractory disease is extremely poor. The role of high-dose therapy and autologous stem cell transplantation (HDT-ASCT) in the treatment algorithm of ENKTL remains unclear. Moreover, there is a paucity of data available on patients undergoing HDT-ASCT for ENKTL outside East Asia.

The objective of this study was to analyse the outcome of Western patients with W.H.O-classified ENKTL who had undergone HDT-ASCT from 2000–2009. The European Group for Blood and Marrow Transplantation (EBMT) database identified 102 such patients. Following an invitation to contribute detailed study-specific data, including investigator review of the original histopathology report, a total of 28 patients with full dataset were included for analysis. All patients had a histological diagnosis of ENKTL, with a natural killer (NK) or cytotoxic T cell phenotype in accordance with the W.H.O classification. A majority of biopsies had demonstrable evidence of EBV by EBER or LMP1 staining. For cases where EBV data was not available, cases were only included if a NK or cytotoxic T cell phenotype was demonstrable together with characteristic clinical and radiological features of ENKTL.

The median age at ASCT was 47.4 years and the median time from diagnosis to ASCT was 22.4 months. There were no discernible difference in characteristics or outcome between the 28 study patients and the remaining patients recorded on the registry. The median follow-up was 32.8 months post-ASCT.

At diagnosis of ENKTL, 57.2% of patients had stage I/II disease. All patients had received at least one line of chemotherapy prior to HDT-ASCT (median 2 lines), whilst only 32.1% had previously received involved-field RT. Remission status at HDT-ASCT was: 43% in first complete remission (CR1); 18% in second or subsequent CR; 21% classified as partial response; and 18% patients with refractory or progressive disease. The 2 year estimates of disease-free survival and overall survival were 40.7% (95%CI: 25.9–64.2) and 52.3% (95%CI: 36.4–75.1) respectively. Disease relapse beyond 12 months was not seen following HDT-ASCT. The 1-year and 2 year non-relapse mortality (NRM) estimates were 11.1% (95%CI 2.7–26.3) and 22.2% (95%CI 8.7 – 39.5) respectively.

The 2 year DFS estimate for patients undergoing HDT-ASCT in CR1 was 63.6% (95%CI 40.7–99.5) compared with 25% (10.7–58.4) for patients not in CR1, although this difference did not reach statistical significance (p=0.068). There was no apparent impact of age, stage or number of previous lines of therapy on NRM, DFS or OS. Interestingly, the 2 year DFS and OS for those with stage III/IV disease were 33.3% (95%CI 13.2–84) and 40% (95%CI 18.7–85.5) respectively, with evidence of a survival plateau after 1 year, indicating a proportion of patients with advanced stage ENKTL can be effectively salvaged by HDT-ASCT.

This is the largest analysis of HDT-ASCT for patients with WHO-classified ENKTL reported from the Western hemisphere. Survival outcomes are comparable to those reported in East Asian cohorts, although detailed comparison is inherently limited by the nature of the study. Non-relapse mortality is higher than anticipated for a relatively young HDT-ASCT population. Most relapses occurred within 1 year of HDT-ASCT. Outcomes are encouraging for patients with advanced disease. Prospective studies are now urgently required to allow more definitive recommendations to be made on the role of HDT-ASCT for patients with ENKTL.