Acute colonic pseudo-obstruction following allogeneic stem cell transplantation successfully treated by neostigmine
A 57-year-old woman with myelodysplastic syndrome relapse was referred to our center in September 2004. She was diagnosed with refractory anemia with excess blasts-2 (RAEB-2) (International Prognostic Scoring System intermediate-2 risk) 6 months earlier [, ], and was administered 2 cycles of chemotherapy with topotecan and cytarabine. Four months after achieving complete remission [], the patient experienced relapse and the disease status was RAEB-1 at the time of referral. While preparing for allogeneic SCT from a partially human leukocyte antigen-mismatched sibling (DR locus) donor, she underwent intensive chemotherapy with idarubicin, fludarabine, cytarabine, and granulocyte-colony stimulating factor.\nIn December 2004, the patient underwent allogeneic SCT with a reduced-intensity conditioning regimen: 30 mg/m2 fludarabine from day -6 to -2 and 3.2 mg/kg Busulfex on days -4 and -3. Considering one DR locus allele mismatch, Campath-1H 20 mg was added from day -7 to -5 and cyclosporine was used for graft-versus-host disease (GVHD) prophylaxis. Her performance status was 1 according to the Eastern Cooperative Oncology Group scale and the blast count at SCT was 6%, consistent with that for RAEB-1. In accordance with our center's policy, postcentrifugal plasmapheresis was performed for the donor-recipient ABO major mismatch for 3 consecutive days before the conditioning. After the infusion of the peripheral blood stem cell graft containing 6.4×106/kg CD34+ cells and 25.5×107/kg CD3+ cells, neutrophil engraftment occurred on day +12.\nOn day +16, the patient complained of abdominal pain and had watery diarrhea of more than 500 mg a day (>5 times/day). She had no skin lesions or hyperbilirubinemia. Blood cell counts showed: 7.86×109/L white blood cells, with 7.51×109/L absolute neutrophils, 156×109/L platelets, and 10.8 g/dL hemoglobin. C-reactive protein level was elevated and the patient developed mild fever. Other laboratory results, including the cytomegalovirus (CMV) antigen assay, were all negative. Stool toxin assay for Clostridium difficile was negative and the standard bacterial stool culture did not detect any causative pathogen. On the next day, sigmoidoscopy was performed to obtain random mucosal biopsies and intravenous (IV) prednisolone therapy at 2 mg/kg was initiated because gut GVHD was clinically suspected. An abdominal radiograph obtained after sigmoidoscopy revealed non-specific findings. The diarrhea had then stopped, and instead, constipation with highly aggravated diffuse abdominal pain had developed. On day +20, large bowel dilation and paralytic ileus was observed on an abdominal radiograph (), and a contrasted computed tomography scan of the abdomen and pelvis () revealed diffuse proximal large bowel gaseous distension with the diameter of the cecum being greater than 6 cm () without any definite obstructive lesion. Colonic and rectal mucosal biopsy results revealed non-specific findings with no evidence of GVHD and the immunohistochemical stain for CMV was negative. On the basis of these findings, ACPO was suspected. Because the patient did not respond to the initial interventions, including total parenteral nutrition with hydration and rectal tube insertion, intravenous neostigmine was administered at 2 mg/day over 5 minutes on day +24, 4 days after the onset of ileus, while tapering the prednisolone. After 4 days of IV neostigmine treatment, the patient began to experience resolution of the ileus, indicated by defecation; decompression of the colon was observed on follow-up abdominal radiographs. From the next day, IV neostigmine was switched to oral pyridostigmine bromide at 60 mg/day. At 6 days after the first administration of neostigmine, complete resolution of the paralytic ileus was achieved, both clinically and radiologically (), without any other complication.