Correlation between the kinetics of CD3+ chimerism and the incidence of graft-versus-host disease in patients undergoing allogeneic hematopoietic stem cell transplantation.
ABSTRACT Graft-versus-host disease (GvHD) remains a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT). Early diagnosis and treatment may improve patient outcomes. A prospective study to investigate the relationship between chimerism kinetics and the development of acute or chronic GvHD was carried out. Split chimerism in association with the onset of GvHD was also analyzed.
Thirty-three patients with hematologic diseases treated with allogeneic HSCT were analyzed. They were conditioned with myeloablative or reduced intensity regimens and grafted with peripheral blood (PB) or bone marrow stem cells. GvHD prophylaxis consisted of cyclosporine and methotrexate. Chimerism evaluation was performed on PB mononuclear cells and purified cell subsets consisting of separated CD3(+) T cells, monocytes (CD14(+)), and granulocytes (CD15(+)). Chimerism analysis was performed at 30, 60, 120, and a median of 200 days after HSCT.
Acute GvHD was diagnosed in 19 patients and chronic GvHD in 16. On day 30, no relation was found between the level of donor chimerism and aGvHD. Upon univariate analysis, decreasing mixed chimerism among CD3(+) and infused CD34(+) cell numbers was significantly correlated with acute GvHD development, while the PB stem cell source, reduced-intensity conditioning regimen, and female donor sex were associated with an increased risk of chronic GvHD. In multivariate analysis, the risk of acute GvHD correlated only with the CD34(+) cell dose, while the risk of extensive chronic GvHD was associated with high CD3(+) donor chimerism on day 30. Patients with versus without split chimerism (T cell vs myeloid lines) did not differ statistically in their incidence of acute GvHD or chronic GvHD.
Our results supported the belief that chimerism kinetics or longitudinal chimerism evaluation is of greater significance than isolated absolute values of the percentage of chimerism at a single point after HSCT. The observations suggest that longitudinal monitoring of chimerism in CD3(+) T-cell subsets is an acceptable method to predict the development of GvHD among patients undergoing HSCT.
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ABSTRACT: Esophagocoloplasty and gastric transposition are 2 major methods of esophageal substitution in children. The purpose of this study is to review the authors' experience with these 2 techniques and compare the complications of these operations to determine whether 1 method emerges superior to the other. A total of 149 children underwent surgery: 115 children underwent esophagocoloplasty, and 34 children underwent gastric transposition. Most patients (113-75.8%) had long-gap esophageal atresia. The operative technique of esophagocoloplasty consisted of the interposition of the transverse colon maintained by a double vascular pedicle based on the left colic vessels and the marginal paracolic arcade. Gastric transposition was performed according to classical technique. The transposition of colon and stomach was performed using blunt mediastinal dissection in all patients without thoracotomy. Complications and mortality of the 2 groups of patients were compared. These complications were classified as minor (cervical anastomosis leak, abdominal evisceration, diarrhea, strictures, and reflux to the interposed viscera) and major (necrosis of transposed viscera, dehiscence of an intra-abdominal or intrapleural suture, torsion of transposed viscera, delayed gastric emptying requiring reoperation, and cologastric anastomosis stricture). There were 2 graft necrosis, 1 (0.8%) in the esophagocoloplasty group and another (2.9%) in the gastric transposition group. Patients who underwent esophagocoloplasty experienced a greater incidence of minor complications (P = .001) and less major complications in comparison with the gastric transposition group (P = .001). All minor complications were treatable and had no consequences. No difference was noted between the 2 groups with regard to the mortality rate (0.9% and 5.9%, respectively, P > .05). Esophagocoloplasty and gastric transposition are satisfactory means of esophageal substitution in children. Considering the incidence of major postoperative complications, esophagocoloplasty must be the first choice for esophageal replacement in children.Journal of Pediatric Surgery 03/2007; 42(3):500-4. · 1.38 Impact Factor
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ABSTRACT: Thirty-eight children (2 months to 26 years of age) underwent esophageal replacement at our institution between 1962 and 1993. Twenty-four patients had esophageal atresia, with the replacement performed at a mean age of 17 months. The remaining patients (37%) had strictures and were older (mean, 7.4 years). Replacement procedures involved the right colon in 61% of cases and the transverse left colon in the others (39%). Sixty-three percent were placed substernally and 37% were done in transthoracic fashion. The average length of stay in the hospital was 34 days (range, 11 to 256 days.) Early complications (within 30 days) included cervical anastomotic leaks (11 patients; 29%) pneumonia (4), would infection (2), pneumothorax/hemothorax (3), wound dehiscence (1), prolonged ventilation (2), vocal cord paralysis (1), Horner's syndrome (1), pancreatitis (1), and perforated graft (1). Despite the incidence of early leaks, only two persisted long-term (more than 3 months). Other late complications included significant proximal strictures (5), and cologastric strictures developed in five patients. Seven cases were considered graft failures (18%), and all of these eventually require graft replacement. Additional problems included redundant graft requiring revision (4) and dumping syndrome (2). There were six cases of intestinal obstruction caused by adhesions. Four of these involved intrathoracic obstruction of the graft and two involved small bowel obstruction. There was only one death, which occurred late and was not related to the primary disease or procedure. Long-term follow-up data were available for 20 patients (53%). The follow-up period ranged from 1 to 33 years (mean, 12 years). Fourteen had excellent results after the initial interposition, being able to eat and function well without any further intervention. Seven patients (18%) have had poor results and 17 (45%) required additional procedures to obtain good functional results. In our experience, the colon continues to be a good option for esophageal replacement, but additional procedures frequently are necessary to optimize the functional outcome. Good results can be expected in the majority of cases, but late problems (ie, redundant colon and poor emptying) are not unusual, and careful follow-up is essential in the management of such patients.Journal of Pediatric Surgery 09/1996; 31(8):1026-30; discussion 1030-1. · 1.38 Impact Factor
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ABSTRACT: Gastric pull-up is the most frequent reconstruction after esophagectomy. In this report we aimed to compare gastric pull-up with colonic interposition in terms of graft function and patient satisfaction. Of 62 patients undergoing esophagectomy, reconstruction was performed by colonic interposition in 11 and gastric pull-up in 51 (without pyloric drainage in 44 and with pyloric drainage in 7). All esophagectomies were performed transhiatally. Patient follow-up ranged from 6 to 132 months (median 14 months). Follow-up examinations were performed 1, 9, 15, and 24 months postoperatively. The following factors were evaluated: time to the start of oral liquid and solid nutrients without vomiting, frequency of regurgitation, presence of pillow staining (night regurgitation), postprandial fullness, and degree of satisfaction during and after eating compared between groups undergoing colonic interposition and gastric pull-up with or without pyloric drainage. Among patients undergoing gastric pull-up, regurgitation was observed in 22% to 27% during follow-up. None of the patients with colonic interposition had reflux or regurgitation. Twenty-five percent of patients with gastric pull-up without drainage and 66% of patients with gastric pull-up plus drainage had reflux esophagitis at 15 months. No esophagitis was observed in patients with colonic interposition during the same period. Overall satisfaction was superior in patients undergoing colonic interposition followed by gastric pull-up with no drainage. Colonic interposition after esophageal resection is a viable option. Our study suggests that function of the replacement is better in this group of patients.Journal of Gastrointestinal Surgery 01/2004; 8(6):675-8. · 2.36 Impact Factor