1. ¹Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA
2. ²Section of Gastroenterology, University of Chicago, Chicago, IL, USA
3. ³Department of Medicine, University of Chicago, Chicago, IL, USA
4. ⁴Department of Pathology, University of Chicago, Chicago, IL, USA

Correspondence: A Artz, E-mail: aartz@medicine.bsd.uchicago.edu

A 61-year-old woman was originally diagnosed with stage IVB follicular lymphoma in 1981 when she presented with lymphadenopathy, fever and night sweats. She was treated with BCNU (carmustine), cyclophosphamide, vincristine and prednisone, and achieved a complete remission. She relapsed in 1994 and over the next decade was treated several times with chemotherapy and localized radiation for recurrent disease. In August 2004, an excisional biopsy of an enlarged cervical lymph node revealed disease transformation into a large B-cell lymphoma. After two cycles of high-dose ifosfamide, etoposide and rituximab, peripheral blood progenitor cells were mobilized. She then received conditioning therapy with BNCU, etoposide, cytarabine and melphalan (BEAM). On day 0, 4.6 10⁶/kg CD34+ autologous cells were infused. Granulocyte recovery occurred on day +10, and platelet recovery on day +15. On day +11, she developed diarrhoea, and was treated with metronidazole for a presumptive diagnosis of Clostridium difficile colitis, despite multiple negative toxin assays. She was discharged on day +15, but the diarrhoea worsened, was >1500 ml on most days, and over the next 6 weeks she lost 15 pounds. Neither skin rash, nor liver function abnormalities developed.

On day +60, the patient was admitted for fever, anorexia and worsening diarrhoea. Broad-spectrum antibiotics were administered. Stool cultures, evaluation for the presence of ova and parasites, and testing for C. difficile toxin were negative. A colonoscopy revealed multiple edematous, inflamed colonic ulcerations (Figure 1). Pathology was consistent with graft-versus-host disease (GVHD) (Figure 2). No viral inclusions were seen, and an immunohistochemical stain for cytomegalovirus (CMV) was negative. Biopsy cultures for CMV and herpes simplex virus were negative, as was a serum CMV polymerase chain reaction (PCR). A thorough examination showed no other evidence of acute or chronic GVHD. Prednisone at 1 mg/kg was begun, and over the next week, the diarrhoea slightly improved from 12 to eight liquid bowel movements daily. Her appetite improved, and her weight stabilized. Ten days after the initiation of prednisone, the patient was readmitted with continued diarrhoea, fever and abdominal cramping. An infectious work-up was again unrevealing, and a repeat colonoscopy demonstrated persistent colitis. Biopsies were again consistent with GVHD. Intravenous methylprednisolone was begun at 2 mg/kg/day in two divided doses, with a marked improvement in her symptoms. The patients bowel movements were regular and well-formed, and she defervesced. She was discharged on 1 mg/kg of oral prednisone daily.

Figure 1.

Endoscopic image of the colon. The colon is diffusely involved with ulcerations associated with inflammation and edema.

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Figure 2.

Colonic biopsy findings. (a) Hematoxylin–eosin ( 200) section demonstrating architectural distortion of crypts and the presence of withered crypts. The glandular epithelium is regenerative in appearance. (b) Higher power view ( 400) of the colonic crypts demonstrating the presence of numerous apoptotic bodies within the gland bases (arrows).

Full figure and legend (173K)

Over the course of the subsequent 3 months, steroids were tapered and the patient remained well. She denied abdominal pain or fever. However, when the prednisone was reduced to 5 mg/day, she again developed severe diarrhoea with eight watery, voluminous bowel movements daily, associated with tenesmus and anorexia. Repeat colonoscopy showed numerous, non-bleeding edematous ulcers throughout the colon. Biopsies did not reveal an increase in apoptotic bodies, in contrast to the prior biopsy specimens. Cultures of stool and of colonic mucosa were again negative. There was no skin rash, and liver function tests were normal. Prednisone was increased to 30 mg daily, with a rapid and marked improvement in her symptoms within 1 week. She remains well and without evidence of disease 14 months after her auto hematopoietic cell transplantation (HCT). Prednisone was successfully tapered approximately 10 months after the second episode of auto GVHD.

Acute GVHD occurs in 50–70% of patients undergoing allogeneic HCT,¹ and is a major cause of post transplantation morbidity and mortality. A syndrome similar to acute GVHD has been reported after auto HCT, both spontaneously and after treatment with cyclosporine and/or interferon, and has been termed autologous GVHD (auto GVHD). Auto GVHD occurs spontaneously in 5–20% of patients undergoing auto HCT,^{2, 3, 4} and in 20–70% of those receiving post transplant immune modulation.^{5, 6, 7, 8}

In comparison with acute allogeneic GVHD, auto GVHD tends to be milder. Most cases have been limited to the skin with only rare gastrointestinal (GI) involvement.^{1, 2, 4, 5, 6} In three recent large series of autologous transplant followed by post transplant immune modulation, GVHD developed in 42% (91/219).^{6, 7, 9} Only six cases of intestinal GVHD occurred, and only one was isolated to the gut.⁷ Auto GVHD of the liver in conjunction with intestinal GVHD has also been reported.¹⁰ A recent series from Seattle suggested that 13% of patients developed GI GVHD after auto HCT.⁴ Almost all cases involved upper GI GVHD. Only three of 90 patients had diarrhoea and no patients had severe diarrhoea.

Our case is, to the best of our knowledge, the first case of severe stage III isolated auto GVHD of the intestine. The auto GVHD occurred spontaneously, in the absence of post transplant immune suppression. Auto GVHD should be considered in the differential diagnosis of severe unexplained diarrhoea after auto HCT.