BACKGROUND: Bone marrow transplantation with minor ABO incompatibility may be followed by moderate delayed hemolysis of the recipient's red cells by donor‐derived ABO antibodies. This reaction may be more severe after transplantation of peripheral blood progenitor cells (PBPCs). CASE REPORT: A 16‐year‐old boy underwent an allogeneic PBPC transplant from his HLA‐mismatched mother as treatment for acute myeloblastic leukemia that had proved resistant to induction chemotherapy. Transfusion of the unmanipulated PBPCs proceeded without any complication, despite the difference in ABO blood group (donor, O Rh‐positive; recipient, A Rh‐positive). On Day 7, a rapid drop in hemoglobin to 4 g per dL was observed, which was attributed to a massive hemolysis. All the recipient's group A red cells were destroyed within 36 hours. This delayed and rapidly progressive hemolytic anemia was not associated with the transfusion of the donor's plasma. Rather, the anti‐A titer increased in parallel with marrow recovery, which suggested an active synthesis of these antibodies by immunocompetent cells from the donor against the recipient's red cells. The mother's anti‐A titer was retrospectively found to be 2048. Her unusually high titer is probably due to prior sensitization during pregnancies. On Day 12, the patient developed grade IV graft‐versus‐host disease, which proved resistant to all treatments instituted and led to his death on Day 35. CONCLUSION: PBPC transplantation with minor ABO incompatibility may be associated with significant risk of massive delayed hemolysis.

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...

Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the study of these receptors in vivo with positron emission tomography (PET). Altanserin is a 4-benzoylpiperidine derivative with a high affinity and selectivity for S2 receptors in vitro. Dynamic PET studies were carried out in nine normal volunteers with high-specific activity (376-1,680 mCi/mumol) [18F]altanserin. Arterial blood samples were obtained and the plasma time-activity curves were corrected for the presence of labeled metabolites. Thirty minutes after injection, selective retention of the radioligand was observed in cortical areas, while the cerebellum, caudate, and thalamus had low radioactivity levels. Specific binding reached a plateau between 30 and 65 min postinjection at 1.8% of the injected dose/L of brain and then decreased, indicating the reversibility of the binding. The total/nonspecific binding ratio reached 2.6 for times between 50 and 70 min postinjection. The graphical analysis proposed by Logan et al. allowed us to estimate the binding potential (Bmax/KD). Pretreatment with ketanserin was given to three volunteers and brain activity remained uniformly low. An additional study in one volunteer showed that [18F]altanserin can be displaced from the receptors by large doses of ketanserin. At the end of the study, unchanged altanserin was 57% of the total plasma activity. These results suggest that [18F]altanserin is selective for S2 receptors in vivo as it is in vitro. They indicate that [18F]altanserin is suitable for imaging and quantifying S2 receptors with PET in humans.

Summary:Adequate infection prophylaxis and empirical antibiotic therapy are of critical importance after hematopoietic stem cell transplantation (HSCT). We examined the evolution of bacterial susceptibility to antibiotics in 492 patients (198 allografts and 294 autografts) transplanted between 1982 and 1999 and evaluated whether ciprofloxacin prophylaxis and an empirical antibiotic regimen (glycopeptide + third-generation cephalosporin) were still valid. We collected all susceptibility tests performed during the initial hospitalization on blood cultures as well as routine surveillance cultures and analyzed susceptibility to ciprofloxacin and to major antibiotics used in our unit. Gram-positive cocci rapidly became resistant to ciprofloxacin (susceptibility around 70% in 1990 to less than 20% in 1998) but sensitivity to glycopeptides remained unaltered. There was a rapid decline in the number of patients colonized with Gramnegative bacilli in the early years of ciprofloxacin prophylaxis. However, susceptibility to ciprofloxacin fell sharply from around 90% in 1990 to around 30% in 1999. In parallel, susceptibility to ceftazidime also decreased to less than 80% in recent years. Piperacillin (؎ tazobactam) did not show any variation over time and its efficacy remained too low (about 60%). Imipenem as well as recently introduced cefepim and meropenem showed stable and excellent profiles (Ͼ90% susceptibility). In conclusion: (1) quinolone prophylaxis has now lost most of its value; (2) the choice of a thirdgeneration cephalosporin for empirical antibiotic therapy may no longer be the best because of the emergence of Gram-negative strains resistant to ␤-lactamases, such as Enterobacter sp. More appropriate regimens of empirical antibiotic therapy in HSCT recipients may be based on the use of a carbapenem or fourth-generation cephalosporin.

The administration of cyclosporin A (CyA) after autologous haematopoietic stem cell transplantation (HSCT) induces a systemic autoimmune syndrome mimicking graft‐vs.‐host disease (GVHD). This syndrome, termed autologous GVHD has notable anti‐tumour activity in animal studies. We intended to induce autologous GVHD with CyA in patients undergoing an autologous HSCT. We prospectively studied 118 patients with miscellaneous malignancies undergoing an autologous HSCT with low‐dose CyA to characterize the clinical syndrome, its frequency and clinical course, and to determine the factors affecting its incidence. Patients received CyA from d −1 through to d 28, first starting at 2 mg/kg intravenously and then orally as soon as feasible. The dose was adjusted to achieve pre‐dose blood levels around 100 ng/ml. A skin biopsy was performed when a skin rash was observed. Thirty‐three percent of the patients developed clinical GVHD: clinical stage 1 in 21 patients, stage 2 in seven patients, and stage 3 in three patients. Although total body irradiation (TBI) or high‐dose cyclophosphamide were previously thought to be needed, autologous GVHD occurred in five out of 12 patients (42%) after a preparative regimen with high‐dose melphalan alone. Autologous GVHD was significantly more frequent in patients older than 33 years, in patients who had received high doses of granulocyte‐macrophage colony forming units (CFU‐GM) and in those with a diagnosis of myeloid malignancy, compared with those with lymphoid malignancies or solid tumours. A significant negative association was also found with HLA‐DR6. In lymphoma patients, GVHD occurred more frequently in advanced disease than in first or second complete remission (CR1–2) patients. All other factors studied were not predictive for GVHD. In conclusion, CyA‐induced GVHD is reproducibly and safely induced with doses of CyA adapted to achieve blood levels around 100 ng/ml. In retrospective analysis, there was no survival advantage for patients with GVHD. Phase III trials with this approach are needed to evaluate its anti‐tumoral effect.