Sequential Evaluation of Outcome in Enteropathy Associated T Cell Lymphoma Comparing Standard Therapeutic Approaches – Surgery or CHOP-Like Chemotherapy with a New High Dose Ifosfamide/Methotrexate and Autologous Stem Cell Transplant Regimen: A Prospective Study of Scotland and Newcastle Lymphoma Group
Michal Sieniawski, MD1,
Stephen J Proctor1,* and
Anne L Lennard6,*
1 Haematological Sciences, Newcastle University, Newcastle, United Kingdom, 2 Department of Haematology, Craigavon Area Hospital, Portadown, United Kingdom, 3 Department of Haematology, University Hospital of North Saffordshire, Stoke on Trent, United Kingdom, 4 Department of Haematology, Western General Hospital, Edinburgh, United Kingdom, 5 Staffordshire General Hospital, Stafford, United Kingdom, 6 Department of Haematology, Royal Victoria Infirmary, Newcastle, United Kingdom
Enteropathy associated T-cell lymphoma (EATL) is a rare diseasewith dismal prognosis. At present there are no standardiseddiagnostic or treatment protocols. The SNLG collected 5yrs ofprospective data which uniquely enables us to describe the diseasein a population-based setting. Additionally, we introduce resultsfrom a novel approach with aggressive chemotherapy (CT) andautologous stem cell transplantation (ASCT). From 1994 –1998 all pts diagnosed with lymphoma in Scotland and the Northernregion of England were prospectively registered. Pts with adiagnosis of EATL were evaluated for clinical features, treatmentand outcome. The novel regimen was piloted from 1997 for newpts eligible for intensive treatment. This therapy deliversone cycle of CHOP, followed by 3 courses of IVE (ifosfamide,etoposide, epirubicin), alternating with intermediate dose methotrexate(MTX). Stem cells are harvested after IVE and complete remissions(CR) are consolidated with myeloablative ASCT. During the studyperiod, 4542 pts were diagnosed with non-Hodgkin-lymphoma andof these 54 pts (1.2%) had features of EATL. In the populationof 7.6 million, this equates to an overall incidence of 0.14/100,000per yr. The median age at diagnosis was 57 yrs, 61% of pts weremale. 40% of pts presented with Lugano clinical stage (CS) IIE(serosal penetration involving adjacent organs and tissues),17% CS IV (disseminated extranodal involvement or supradiaphragmaticnodal involvement), 15% CS I (confined to GI-tract), 15% CSII1 (local abdominal involvement) and 12% CS II2 (distant abdominalinvolvement). Two pts had bone marrow involvement. Diagnosisof EATL was made at laparotomy in 91% of pts. Tumour was arisingfrom the small bowel in 96% of pts; in one case involved theduodenum and in another the iliocaecal region. Pain was themost common presenting symptom (81%), followed by weight loss,visceral perforation, nausea/vomiting, bowel upset and subacuteobstruction. Symptoms were present less than a month beforediagnosis in 33% of pts and between 1–6 months in 55%.92% of pts had co-existing coeliac disease (diagnosed priorto diagnosis of EATL in 35% of pts and co-incidently in 58%).30 pts (56%) were treated with surgery and CT, 19 pts (35%)with surgery alone and 5 pts (9%) with CT alone. Of those ptstreated with CT the majority (31/35) received CHOP-like regimens.There were no statistically significant differences betweentreatment groups with the exception of higher number of elderlypts treated with surgery alone. 44 pts died, mostly due to lymphomaor complications. For all pts, median progression free survival(PFS) was 3.4 months and overall survival (OS) 7 months. 5yrPFS and OS for pts treated with CHOP-like CT was 20% and 22%,respectively and no pts treated with surgery alone survived.18 pts were subsequently treated with the new regimen. The medianage was 52.5 yrs, 67% of pts were male, 39% presented with LuganoCS II1, 22% CS I, 22% CS IV, 11% CS IIE, 6% CS II2+E. The bonemarrow was involved in one pt. Site of disease was small bowelin 83% of pts and two patients had involvement of stomach andduodenum and one of small bowel and colon. In all except onept the diagnosis was made at laparotomy. 12 pts (67%) completedall planned treatment, 3 pts had progressing disease duringtreatment, two other did not received ASCT due to poor generalcondition and one pt declined further treatment. Most commonsevere toxicities were pancytopenia, infection, nausea/vomitingand obstruction/perforation. Treatment results were comparedwith historical control group treated with CHOP-like CT. Therewas no difference between the groups according to age, sex andfeatures at presentation. Compared to pts treated with CHOP-likeCT, those in the IVE/MTX group had improved CR at final evaluation(42% vs 72%), 5yr PFS (20% vs 56%; p=0.008) and 5yr OS (22%vs 67%; p=0.001). Additionally, in the IVE/MTX group fewer patientsdied than in the CHOP-like CT group (33% vs 81%; p=0.002). Therewere no treatment related deaths. In a population-based studyof EATL we describe the natural history of the disease in thecontext of current treatments. We propose a new protocol withsignificantly improved outcome and acceptable toxicities. Inconclusion, pts with EATL should be treated with systemic CTand where feasible an aggressive treatment like IVE/MTX –ASCT. We recommend patients should be entered into nationalstudies such as (NCRI 1418) to evaluate this approach further.
Disclosures: No relevant conflicts of interest to declare.