American Journal of Transplantation 2014; 14: 2651–2656 Wiley Periodicals Inc.

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Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.12862

Case Report

Graft-Versus-Host Disease After Simultaneous Pancreas–Kidney Transplantation: A Case Report and Review of the Literature A. P. Rossi1, B. A. Bone1, A. R. Edwards1, M. K. Parker2, R. B. Delos Santos1, J. Hagopian3, C. Lockwood4, A. Musiek2, C. L. Klein1 and D. C. Brennan1,* 1

Transplant Nephrology, Washington University in St. Louis, St. Louis, MO 2 Department of Dermatology, Washington University in St. Louis, St. Louis, MO 3 Department of Pharmacy, Barnes-Jewish Hospital, St. Louis, MO 4 Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO  Corresponding author: Daniel C. Brennan, [email protected]

Graft-versus-host disease (GVHD) after solid organ transplantation is rare and usually fatal. We present, to our knowledge, the second successfully treated case in a simultaneous pancreas–kidney (SPK) transplant recipient. A 29-year-old female with end-stage renal disease from type 1 diabetes mellitus received an SPK transplant from a male donor, with rabbit-antithymocyte globulin induction. Twelve days posttransplant, she was readmitted with abdominal pain, nausea and vomiting. She developed leukopenia, abnormal liver enzymes, fever and a skin rash. Skin biopsy showed interface dermatitis consistent with allergic reaction versus GVHD. Fluorescence in situ hybridization of the skin biopsy showed 28% of cells had a Y chromosome confirming GVHD. Short tandem repeats (STR) enriched for CD3þ cells from peripheral blood showed a mixed chimerism. She was successfully treated with a single plasmapheresis to remove antithymocyte globulin, high-dose steroids, photopheresis and high tacrolimus levels (12–15 ng/mL). Five months after transplantation, she has normal renal function and white blood cell count, normal hemoglobin A1C and no evidence of peripheral blood donor chimerism. In conclusion, early diagnosis of GVHD after SPK transplantation may allow successful treatment. STR enriched for CD3þ may be useful to evaluate the response to therapy. Abbreviations: CMV, cytomegalovirus; EBV, Epstein– Barr virus; ECP, extracorporeal photopheresis; ESRD, end-stage renal disease; FISH, fluorescence in situ hybridization; GVHD, graft-versus-host disease; HBA1c,

hemoglobin A1c; HSCT, hematopoietic stem cell transplantation; MPA, mycophenolic acid; PCR, polymerase chain reaction; POD, postoperative day; PRBC, packed red blood cells; rATG, rabbit-antithymocyte globulin; SCr, serum creatinine; SOT, solid organ transplant(s); SPK, simultaneous pancreas–kidney; STR, short tandem repeats; WBC, white blood cell Received 23 April 2014, revised 02 June 2014 and accepted for publication 03 June 2014

Introduction Graft-versus-host disease (GVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT). This T cell–mediated disorder consists of donor immune cells (the graft) recognizing the transplant recipient (the host) as foreign, thereby initiating an immune reaction against the host. Common manifestations include fever, maculopapular rash, vomiting, diarrhea and abnormal liver enzymes (1). Solid organ transplants (SOT) have less lymphoid tissue than HSCT and therefore GVHD is rare (2). The incidence of GVHD after small bowel and liver transplantation is estimated at 5–10% and 1–2%, respectively (3,4). To date, 12 cases of GVHD following pancreas transplantation have been reported. Five were simultaneous pancreas–kidney (SPK) transplants, and only one survived (5–12). We present the second successfully treated case of GVHD in an SPK recipient and discuss the use of serial short tandem repeats (STR) DNA analyses for early diagnosis and monitoring response to therapy.

Case Report A 29-year-old African American female with end-stage renal disease (ESRD) presumed secondary to type 1 diabetes mellitus and possible hereditary nephritis underwent an SPK transplant. She was diagnosed with type 1 diabetes mellitus at the age of 13. Additional past medical history included bilateral hearing loss requiring hearing aids, hypertension, anemia and menorrhagia. She underwent hemodialysis thrice weekly through a left upper extremity 2651

Rossi et al

arterio-venous fistula. Family history was significant for hearing loss in her mother and sister. Her mother died at the age of 36 from heart disease. Her sister also had type 1 diabetes mellitus and ESRD. The patient received a 1A, 1B, 1DR HLA-mismatched, cytomegalovirus (CMV) donor seropositive into recipient seronegative, Epstein–Barr virus recipient seropositive SPK transplant from a male donor. Induction immunosuppression included methylprednisolone 500 mg intraoperatively and rabbit-antithymocyte globulin (rATG) 7 mg/kg given over 4 days. She was transitioned to maintenance prednisone 20 mg daily, mycophenolic acid (MPA) 360 mg twice daily and tacrolimus 1 mg twice daily, with target tacrolimus levels of 8–10 ng/mL. Infectious disease prophylaxis consisted of sulfamethoxazole/trimethoprim 800/ 160 mg daily, valganciclovir 900 mg daily and fluconazole 100 mg daily. She had prompt graft function and was discharged on postoperative day (POD) 8 with serum creatinine (SCr) of 1.3 mg/dL and normal glucose, amylase and lipase. On POD 12 she was readmitted with lower abdominal pain, nausea and nonbloody emesis. White blood cell (WBC) count was 16.9/mm3, amylase 201 U/L (normal 28–100 U/L) and lipase 197 U/L (normal 20–50 U/L). SCr, glucose and liver function tests were normal. An abdomen and pelvis computed tomography showed closed-loop small bowel obstruction. She underwent an exploratory laparotomy with adhesiolysis; however, a yellow-whitish fluid was noted throughout her abdominal cavity and empiric vancomycin, meropenem and micafungin were started. No allograft biopsy was performed during laparotomy. Antibiotics were discontinued after 48 h of negative cultures. Two days later, she developed a fever of 39.48C and antibiotics were restarted. Whole blood CMV polymerase chain reaction, blood, urine and sputum cultures were rechecked and remained negative. A nasopharyngeal swab for common viral infections was positive for rhinovirus. To evaluate for an occult infection or an early posttransplant lymphoproliferative disorder, the patient underwent a whole body positron emission tomography scan which showed increased fluorodeoxyglucose uptake in the gastric lumen. A follow-up upper endoscopy revealed gastritis but gastric mucosa biopsies were unremarkable. She received one unit of packed red blood cells (PRBC) on two different occasions given a hemoglobin

Graft-versus-host disease after simultaneous pancreas-kidney transplantation: a case report and review of the literature.

Graft-versus-host disease (GVHD) after solid organ transplantation is rare and usually fatal. We present, to our knowledge, the second successfully tr...
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