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Gut. 2007 September; 56(9): 1325.
PMCID: PMC1954955

Remission and relapse of Crohn's disease following autologous haematopoietic stem cell transplantation for non‐Hodgkin's lymphoma

Autologous haematopoietic stem cell transplantation (HSCT) for Crohn's disease has been described by Oyama and co‐workers as producing remission in 11 of 12 patients with refractory Crohn's disease after a median follow up of 18.5 months.1 They postulated that autologous HSCT was useful for refractory Crohn's disease. We report the case of a 32 year old woman with biopsy proven Crohn's disease diagnosed when she was 16 years old. Her mother also suffered from Crohn's disease. She developed a KI1 positive anaplastic non‐Hodgkin's lymphoma (NHL) three years later, treated successfully with ablative CHOP chemotherapy and autologous HSCT, inducing remission for the past 12 years (and she remains in remission on no treatment). As a consequence of her autologous HSCT she also went into long term remission from her Crohn's disease, but relapsed after eight years. She was a smoker, but was on no maintenance treatment for Crohn's disease in this eight year period. She developed abdominal pain and bloody diarrhoea and underwent a colonoscopy, and a biopsy proved the recurrence of her colonic Crohn's disease. She was treated with corticosteroids and 5‐aminosalicylates, which induced temporary remission. However, she subsequently had two relapses over the past two years, with diarrhoea, histologically proven erythema nodosum, and seronegative arthropathy. She was treated with reducing courses of corticosteroids with prompt resolution of her symptoms. There is no evidence of relapse from her NHL, and long term treatment with immunosuppressive agents or infliximab is under consideration but has been deferred because of a small increased risk of lymphoma associated with these agents (though it is not known whether this is attributable to Crohn's disease, immunosuppression alone, or a combination of the two2). Genotyping revealed no CARD15 mutations (R702W, G908R, and L1007fs).

Our case is the longest reported “follow up” of autologous HSCT in Crohn's disease and raises some interesting questions with regard to the long term efficacy of autologous HSCT for Crohn's disease, as our patient appeared to be in complete long term remission and was apparently “cured” of her Crohn's disease for eight years before relapsing. We postulate that the autologous HSCT led to ablation of “activated” T cells for a prolonged period (resetting the immune system) but that her genetic predisposition (positive family history), allied to other environmental factors (smoking), subsequently led to her disease relapse. This is in keeping with the current hypothesis of the aetiopathogenesis of Crohn's disease and suggests that autologous HSCT will not provide a long term “cure” for this disorder. Allogenic HSCT may be more appropriate,3 albeit at a much greater risk of treatment related complications such as graft versus host disease. This is further supported by the results of allogenic HSCT for Crohn's disease, where the only relapse occurred in a patient who developed a mixed donor–host haematopoietic chimerism following allogenic HSCT.4 Furthermore, in the study by Oyama and co‐workers, there were two relapses in the short term and only two patients achieved treatment‐free remission for more than three years.5

Footnotes

Conflict of interest: None declared.

References

1. Oyama Y, Craig R, Traynor A E. et al Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease. Gastroenterology 2005. 128552–563.563 [PubMed]
2. Kandiel A, Fraser A G, Korelitz B I. et al Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6‐mercaptopurine. Gut. 2005 Aug 541121–1125.1125 [PMC free article] [PubMed]
3. Hinterberger W, Hinterberger‐Fischer M, Marmont A M. Clinically demonstrable anti‐autoimmunity mediated by allogeneic immune cells favourably affects outcomes after stem cell transplantation in human autoimmune disease. Bone Marrow Transplant 2002. 30753–759.759 [PubMed]
4. Lopez‐Cubero S O, Sullivan K M, McDonald G B. Course of Crohn's disease after allogeneic marrow transplantation. Gastroenterology 1998. 114433–440.440 [PubMed]
5. Barkholt L, Löfberg R. Resetting the immune system in refractory Crohn's disease: is autologous hematopoietic stem cell transplantation the way forward? Gastroenterology 2005. 128786–789.789 [PubMed]

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