Bronchiolitis obliterans organizing pneumonia and ulcerative colitis after allogeneic bone marrow transplantation

Abstract

Summary:A 37-year-old man with acute myeloblastic leukemia in first remission developed ulcerative colitis and bronchiolitis obliterans organizing pneumonia (BOOP) 7 months after bone marrow transplantation (BMT) from an HLA-matched brother who suffered from severe Crohn's disease. BOOP occurred 20 days after idiopathic interstitial pneumonia, in the context of severe ulcerative colitis. Lung and colon biopsies showed no signs of CMV infection or GVHD. The patient was treated with oral methylprednisolone 1 mg/kg/day and his clinical status and chest X-ray improved slowly. Remarkably, the symptoms of colitis also resolved with prednisone therapy and he is now symptom-free. We hypothesize that ulcerative colitis may have been transmitted from donor to recipient (adoptive autoimmunity) and that it was complicated by BOOP. However, other factors such as CMV may have contributed to the occurrence of BOOP. Keywords: allogeneic bone marrow transplantation; autoimmune diseases; ulcerative colitis; BOOP; adoptive autoimmunity Bronchiolitis obliterans organizing pneumonia (BOOP) is a rare cause of diffuse infiltrative lung disease. It may be idiopathic or occur in association with infections, drugs or miscellaneous neoplastic or inflammatory diseases. The first case of BOOP following bone marrow transplantation (BMT) was described in 1990. 1 Since then, six additional cases of BMT-associated BOOP have been reported (Table 1), including two successive episodes in a single patient undergoing two BMT procedures. 2-4 BOOP has also been described in several patients with inflammatory bowel disease. 5 We report a new case of BMT-associated BOOP which developed in the recipient of a marrow transplant from a donor who suffered from Crohn's disease. As the patient simultaneously developed ulcerative colitis and BOOP about 6 months after BMT, this observation could Correspondence: Dr Y Beguin, University of Liège, Department of Hematology, CHU Sart-Tilman, 4000 Liège, Belgium Received 15 August 1997; accepted 11 November 1997 constitute a case of adoptive autoimmunity in which transmission from donor to recipient of inflammatory bowel disease could have contributed to the pathogenesis of BMTassociated BOOP. Case reportThe patient, a 37-year-old man with acute myeloblastic leukemia in first remission, received a genotypically HLAidentical BMT from his brother in March 1995. The donor was negative for cytomegalovirus (CMV) on serology but had suffered from severe Crohn's disease for the past 15 years, which was treated with sulfasalazine and azathioprine. The latter was stopped 3 weeks before the transplant. The recipient was positive for CMV. Pre-transplant pulmonary function tests were normal. Conditioning consisted of cytarabine 12 g/m 2 , cyclophosphamide 120 mg/kg and single dose total body irradiation (TBI) 8 Gy. Graft-versushost disease (GVHD) prophylaxis was carried out with short methotrexate and cyclosporine (CsA).The initial post-transplant course was complicated by grade 1 acute skin GVHD that resolved after increasing t...

Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation

“…50 Among 19 reported HSCT recipients with BOOP, the overall case fatality was 21%. 11,16,[48][49][50][51][52][53][54][55] …”

“…16,[48][49][50][51][52][53]55 The duration and dosage of corticosteroid therapy have not been clearly defined.…”

“…16,50,51 The presenting symptoms include dry cough, dyspnea, and fever, [48][49][50] with onset between 1 and 13 months following transplant. 16,[48][49][50][51][52][53][54][55] Diagnostic evaluation BOOP should be included in the differential diagnosis of bilateral airspace disease in HSCT recipients, especially if they do not respond to antibiotics for presumed pneumonia. PFTs show a restrictive defect, decreased DLCO, and normal expiratory flow.…”

Clinical features of allogeneic hematopoietic stem cell transplantation-associated organizing pneumonia

“…Baron et al 21 summarized eight previously reported cases of HOP and found that seven out of eight patients received TBI containing regimen. Of note is the fact that incidence of HOP was significantly higher in patients with irradiation-containing regimens than in patients with conventional conditioning regimens, such as those containing BU plus CY, for which no TLI is administered (12 of 342 patients versus 0 of 261 patients, respectively; Po0.005).…”

“…However, given that most patients showed a preceding episode of CMV reactivation within the time frame of HOP onset, it is tempting to speculate on a possible association between HOP and CMV reactivation, which has been among previously reported risk factors. 21 The etiology of HOP thus remains unclear, but may be complicated by several plausible factors, including direct immunological reaction, irradiation and underlying infection or aspiration.…”