The study was performed after the approval by the SNUH institutional review board (IRB; No. E-1108-106-375). A 22-month-old girl was diagnosed with acute myeloid leukemia. She received induction chemotherapy with enocitabine (300 mg/m2
by intravenous [IV] administration for 10 days), idarubicin (10 mg/m2
by IV administration for 3 days), cytarabine (30 mg by intrathecal injection for 1 day), and 6-thioguanine (100 mg/m2
orally for 10 days) [6
]. She achieved complete remission, and after 3 cycles of consolidation chemotherapy, she received an allogeneic peripheral stem cell transplantation from a sex-mismatched but fully HLA-matched unrelated donor. The mean dose of cells infused was 34.7×108
/kg for total nucleated cells, 29.8×108
/kg for mononuclear cells, and 33.6×106
/kg for CD34+
cells. The conditioning regimen comprised busulfan (0.8 mg/kg by IV administration for 4 days), fludarabine (40 mg/m2
by IV administration for 6 days), and anti-thymocyte globulin (ATG) (2.5 mg/kg by IV administration for 3 days). Tacrolimus and short-course methotrexate were administered for GVHD prophylaxis. Tacrolimus was started 2 days before stem cell infusion (continuous IV infusions at 0.03 mg/kg/day), and MTX was started 1 day after stem cell infusion (IV administration at 15 mg/m2
). On day 12 of transplantation, the absolute neutrophil count (ANC) rose above 1.0×109
/L), and the platelet count was 121×109
/L. The patient was discharged on day 19 without any symptoms or signs of acute GVHD.
On day 138, the patient was admitted to the hospital for persistent cough for more than 1 week. Chest computed tomography (CT) showed diffuse interstitial infiltration (). Piperacillin/tazobactam, ganciclovir, and sulfamethoxazole/trimethoprim were administered for the treatment of pneumonia. Laboratory examination revealed elevated levels of liver enzymes (AST, 206 IU/L; ALT, 243 IU/L). Blood culture, urine culture, blood Epstein-Barr virus (EBV) antibody, blood cytomegalovirus (CMV) antigen, and nasopharyngeal aspiration respiratory viral study were all negative. After admission, the patient's cough subsided, and the findings on chest radiograph improved, but the patient developed a fever on day 145 followed by a skin rash on the whole body and hematochezia on day 147. The liver enzyme levels showed persistent elevation, and the total bilirubin level also began to rise, peaking at 2.9 mg/dL on day 146. A skin biopsy was performed; pathological examination revealed interface vacuolar change with several dyskeratotic cells consistent with chronic GVHD. Liver biopsy revealed lymphocytic/eosinophilic infiltration in the portal triad with diffuse bile duct damage, and focal crypt atrophy was shown on colon biopsy specimens, which are consistent with chronic GVHD. Treatment for chronic GVHD with prednisolone (Pd) and cyclosporine A (CsA) was started on day 163.
Chest CT image obtained on day 138 shows multifocal subsegmental atelectasis and increased interstitial marking.
A CMV antigenemia assay performed on day 175 was positive, indicating CMV infection. Therefore, ganciclovir therapy was initiated. The colon biopsy specimen tested negative for CMV infection.
Because of persistent diarrhea and hyperbilirubinemia (total bilirubin, 11.1 mg/dL; direct bilirubin, 5.9 mg/dL), a salvage regimen for chronic GVHD with tacrolimus/MMF and Pd was started on day 182. Hematochezia increased; therefore, a bleeding scan was performed on day 214. However, no bleeding focus was identified. Hematochezia subsided, and the total bilirubin level returned to near normal by day 260, but abdominal pain and ileus persisted. Therefore, an upper gastrointestinal and small bowel contrast study was performed. The result showed narrowing and partial obstruction of the proximal-to-distal small bowel (), and small bowel resection was performed on day 270. During laparotomy, diffuse constriction was observed in the terminal ileum (). The results of pathological examination were consistent with chronic GVHD, showing severe loss of mucosal epithelium, many basal single cell apoptotic bodies, crypt dropout, and submucosal/subserosal fibrosis ().
Ten hours after upper GI contrast study on day 264. Luminal narrowing of the small bowel with dilatation of the proximal bowel can be seen.
Surgical specimen showing a segment of the small bowel. Diffuse constriction of the muscle layer is observed in the terminal ileum. The length of the obstructed segment is approximately 15 cm.
Pathological images are consistent with chronic GVHD (H&E staining).
Following laparotomy, abdominal pain and diarrhea subsided. Oral feeding was initiated on day 276 (postoperative day 6), and the patient's oral intake increased successfully. Liver enzymes, total normalized bilirubin, and chest radiograph findings also improved. The patient was discharged on day 290. The patient continued MMF therapy until day 378 and tacrolimus therapy until day 638. She has been disease-free for 4 years after HSCT. She is not taking medications other than vitamin B12 and does not have gastrointestinal problems.