Treatment of Enteropathy Associated T Cell Lymphoma with Combination Chemotherapy Followed by Autologous Stem Cell Transplantation.
Authors: Bishton Mark J. , Haynes Andrew P. , Byrne Jenny L. , Russell Nigel H. 
Published: October 2019

Background: Enteropathy associated T cell lymphoma (EATL) accounts for less than 1% of all Non-Hodgkins lymphomas and ~5% of gastro-intestinal lymphomas, and is strongly associated with Coeliac disease. Treatment has traditionally involved Doxorubicin based combination chemotherapy such as CHOP although there is no consensus on guidelines for treatment. Patients are often emaciated due to malabsorbtion at diagnosis and often tolerate treatment poorly with death occurring due to perforation and gastro-intestinal bleeding. There appears to be a high relapse rate in those who complete treatment, and overall survival rates are agreed to be around 20% at 5 years.

Methods: Consecutive patients with biopsy proven Enteropathy associated T cell lymphomas were treated in a single institution. All patients were made nil by mouth, and given intra-venous fluids with oral ciprofloxacin and metronidazole as gut prophylaxis 48 hours prior to chemotherapy. When the risk of perforation was considered to be over continuous NJ feeding was instituted with regular dietetic support. 2 cycles of a combination of Ifosphamide, Etoposide and Epirubicin (IVE) were given 4 weeks apart. Patients had peripheral blood stem cells mobilised with G-CSF support following the second cycle. After stem cell harvest 2 cycles of high dose methotrexate (3g/m2) with folinic acid rescue were given. Following this, patients were admitted for consolidation with autologous stem cell transplantation with BEAM conditioning.

Results: The median age of the patients was 56 years (40–59). 5 were diagnosed following laporotomy and small bowel resection and one by lymph node biopsy. All but 1 patient had stage 1E disease. 3 were known to have coeliac disease previously while 3 were diagnosed post-operatively. All 6 patients were able to tolerate the planned treatment with no deviation from protocol and there was no transplant related mortality. There were no episodes of perforation or GI bleeding. One patient was unable to be harvested due to sepsis and was mobilised with G-CSF alone prior to methotrexate being given. All patients suffered with severe diarrhoea and weight loss ranging from 5–11 kilograms during their autograft, despite continuous parenteral feeding. Standard CT restaging showed five patients achieved a complete remission (CR) and one other a very good partial response (VGPR). Of the 6 patients, 2 had florid relapse at 0.21 and 1.71 years post PBSCT and subsequently rapidly died due to intestinal perforation. The other 4 remain alive and in CR at 1.83, 3.35, 3.67 and 4.32 years following transplant respectively.

Conclusion: EATL is a rare extra-nodal T cell lymphoma with a very poor prognosis with standard treatment, and large case series take many years to build. EATL is also often added to series of other high-grade T cell lymphomas or GI non Hodgkin’s lymphomas, making it difficult to determine optimal management. In our series of patients there were no serious complications following gut sterilisation and induction and consolidation chemotherapy, and despite marked weight loss all were able to tolerate PBSCT. 4 out of 6 patients (66.7%) remain alive and in a sustained CR, while 2 suffered an early relapse and rapidly died. We conclude that this regimen appears to be extremely efficacious in the treatment of EATL.