We analyzed the outcome of 692 patients with severe aplastic anemia (SAA) receiving transplants from HLA-matched siblings. A total of 134 grafts were peripheral blood progenitor cell (PBPC) grafts, and 558 were bone marrow (BM) grafts. Rates of hematopoietic recovery and grades 2 to 4 chronic graft-versushost disease (GVHD) were similar after PBPC and BM transplantations regardless of age at transplantation. In patients older than 20 years, chronic GVHD and overall mortality rates were similar after PBPC and BM transplantations. In patients younger than 20 years, rates of chronic GVHD (relative risk [RR] 2.82; P ؍ .002) and overall mortality (RR 2.04; P ؍ .024) were higher after transplantation of PBPCs than after transplantation of BM. In younger patients, the 5-year probabilities of overall survival were 73% and 85% after PBPC and BM transplantations, respectively. Corresponding probabilities for older patients were 52% and 64%. These data indicate that BM grafts are preferred to PBPC grafts in young patients undergoing HLAmatched sibling donor transplantation for SAA. IntroductionTransplantation of bone marrow (BM) from an HLA-matched sibling donor is an effective treatment for severe aplastic anemia (SAA) with long-term survival in excess of 80% and graft failure rates of approximately 10%. [1][2][3][4][5][6][7] Unpublished data (January 2007) from the European Group for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR) suggest approximately 60% of HLA-matched sibling donor transplantations for SAA now use peripheral blood progenitor cell (PBPC) grafts. A similar switch to PBPC over BM grafts is reported in leukemia transplantations. [8][9][10] The higher rate of chronic graft-versus-host disease (GVHD) may be offset by lower relapse rates in some settings. In contrast, there is no perceived benefit of chronic GVHD for SAA. Further, few data on PBPCs for SAA are reported. [11][12][13][14][15] In a preliminary analysis from our group, PBPC grafts appeared to contribute to higher mortality. 16 Here, we report chronic GVHD and long-term overall survival rates in 134 PBPC recipients and 558 BM recipients of HLA-matched sibling donor transplants for SAA. Patients, materials, and methods PatientsData on patients undergoing their first PBPC and BM HLA-matched sibling transplantation from 1995 to 2003 were obtained from the EBMT and the Statistical Center of the CIBMTR at the Medical College of Wisconsin. Only patients who received transplants at centers that provided a minimum of 12 months of follow-up on all their surviving patients were included. The Institutional Review Board of the Medical College of Wisconsin approved this study. Informed consent was obtained in accordance with the Declaration of Helsinki. Statistical methodsThe probabilities of hematopoietic recovery (neutrophil count Ն 0.5 ϫ 10 9 /L for 3 consecutive days and platelet count Ն 20 ϫ 10 9 /L for 7 days, unsupported) and acute and chronic GVHD were calculated using the cum...
Allogeneic PBSC results in faster neutrophil and platelet engraftment and a higher incidence of chronic GVHD than BM. However, acute GVHD, TRM, relapse, survival, and LFS were similar in patients receiving PBSCs versus BM.
Summary:We noted a significant decline in the serum concentrations of citrulline of 32 haematopoietic stem cell transplant recipients following intensive myeloablative therapy during the first 3 weeks after transplantation when patients have oral mucositis, a markedly disturbed gut integrity (L/R ratio) and are most at risk of infection and other severe complications. Closer inspection of the citrulline concentrations of 12 patients confirmed that the decline did indeed correspond to the onset of oral mucositis and altered gut integrity. Since serum citrulline is a reliable biochemical marker of small bowel enterocyte mass in humans with villous-atrophy-associated diseases, it may prove a useful marker for intestinal mucosal damage induced by chemotherapy, allowing the relationship between gut mucosal damage and post-transplant complications including infections to be explored more readily. Mucositis is a manifestation of mucosal barrier injury and is the most frequent cause of morbidity associated with the myeloablative conditioning treatment used to prepare for haematopoietic stem cell transplantation (HSCT). 1 Oral mucositis is easy to recognise, whereas detection of intestinal mucosal injury relies essentially on nonspecific symptoms such as nausea, vomiting, diarrhoea and abdominal cramps, which affect almost every HSCT recipient. An alternative means of recognising gut mucosal barrier injury is required if it is to be better understood and managed. Alterations in permeability and loss of epithelial surface are features of gut injury that can be detected by sugar permeability tests which are noninvasive and generally accepted as a surrogate marker of gut damage in patients treated for cancer. 2 However, sugar permeability tests are cumbersome and wholly dependent on patient compliance. A marker of intestinal injury that could be determined in blood would be ideal, but none has been described so far. Citrulline might prove valuable in this regard since it is an end product of glutamine metabolism of small intestinal enterocytes, cells which lack the necessary cytosolic enzymes to convert the amino acid to arginine. 3 Blood concentrations of citrulline directly reflect cell mass of the small intestine since the small intestine is the principal source of the amino acid, and it is not metabolised by the liver. 4 In mice, citrulline levels were used to quantify acute small bowel epithelial damage after single-dose whole-body irradiation. 5 The high-dose chemotherapy used to prepare patients to receive an HSCT injures the small intestine by inducing crypt apoptosis, hypoplastic villous atrophy and loss of enterocytes. 6 We determined the amino-acid profiles in the serum of a cohort of 32 HSCT recipients who had participated in a prospective randomised placebo-controlled study approved by the local Ethics Committee, the aim of which was to investigate the possible benefits of parenteral nutrition (PN) supplemented with glutamine-dipeptide. As citrulline was included, we were able to relate the concentrations tempo...
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