Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked hyper-IgM syndrome (XHIM), or hyper-IgM syndrome type 1 (HIGM1), is a rare primary immunodeficiency disorder susceptible to recurrent bacterial infection and opportunistic infection such as Pneumocystis carinii and Cryptosporidium parvum. The long-term outcome is quite poor, and allogeneic hematopoietic stem cell transplantation (HSCT) offers the only cure. Seven patients with XHIM, from age 3 to 19 years (mean 11.3 years), underwent allogeneic HSCT in our institution. Details of pre- and post-transplantation data and transplantation procedure were analyzed retrospectively. The donors were HLA-identical siblings for three patients and HLA-identical unrelated donors for four patients. All but one received conventional conditioning regimen consisting of busulfan and cyclophosphamide and prophylaxis for graft-versus-host disease (GVHD) consisting of cyclosporine and methotrexate. Five out of seven patients are alive and well with normal CD40L expression, and four of these five are free of intravenous immunoglobulin supplementation. The two patients who died had prolonged episodes of severe and recurrent infections and organ damage. We conclude that conventional allogeneic HSCT from HLA matched related or unrelated donors is curative and feasible for XHIM patients, if performed before significant infections and organ damage occur. For the high-risk patients, an alternative approach including nonmyeloablative HSCT may be more feasible.
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PMID:Allogeneic hematopoietic stem cell transplantation for seven children with X-linked hyper-IgM syndrome: a single center experience. 1511 94

We analyzed 30 peripheral blood stem cell transplantations (PBSCT) from 25 human leukocyte antigen (HLA) matched sibling donors (MSD) and 4 HLA-matched unrelated donors (MUD) in 29 patients, done between November 1996 and March 2003. Patients aged 3 to 17 years underwent allogeneic PBSCT for malignant (16 patients) and non-malignant (13 patients) diseases. Sibling donors aged 3 to 23 years were given granulocyte colony-stimulating factor (G-CSF) 5-10 microg/kg/day for 4 to 5 days. All but one of the 29 donors underwent one single leukapheresis for stem cell collection. The patients received a median of 4.2 x 10(6) CD34+ cells/kg of body weight, they all engrafted after a median of 13.5 days (range 10-25 days). Acute graft-versus-host disease (GVHD) grade II to IV developed in 11 of 26 MSD transplants and in all 4 patients after MUD PBSCT. Eleven of 27 evaluable patients experienced chronic GVHD. After a median follow-up of 662 days, 20 out of 29 patients (69%) are alive, three of them need systemic immunosuppression for chronic GVHD. Six patients experienced relapse of their underlying malignant disease, one of them still alive in complete remission. Two patients died of grade IV acute GVHD and two others due to an opportunistic infection. Based upon our experience, PBSCT is a feasible and safe method for both pediatric donors and patients. It is associated with rapid engraftment, no greater incidence of acute but a higher incidence of chronic GVHD as compared to bone marrow transplantation (BMT) and therefore suitable mainly for children suffering from malignant diseases.
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PMID:Allogeneic peripheral blood stem cell transplantations in children--a single center experience. 1519 Apr 20

Selective depletion of alloreactive T cells from allogeneic stem cell grafts can reduce graft-versus-host disease (GVHD) while preserving beneficial effects of T cells including facilitation of engraftment, protection against opportunistic infection, and reduced relapse risk. Memory T cells (CD62L(-)) represent a population of T cells that have previously encountered pathogens and may contain fewer T cells capable of recognizing neoantigens including recipient allogeneic antigen (aAg). We investigated whether human naive (CD62L(+)) or memory (CD62L(-)) T cells had different capacities to respond to aAg by assessing their ability to proliferate in response to and lyse HLA-mismatched Epstein-Barr virus-transformed B cells. Freshly sorted and in vitro expanded CD62L(-) memory T cells were less responsive to aAg stimulation than were CD62L(+) naive T cells but contained higher levels of cytomegalovirus (CMV)-specific T cells. Analysis of T cell receptor (TCR) repertoire showed restricted TCR diversity in the memory T-cell population possibly due to selection associated with chronic exposure to common pathogens. Memory T cells may represent a donor cell subpopulation suitable for enhancing immune reconstitution without increasing the risk of GVHD.
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PMID:Human CD62L- memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells: potential for adoptive immunotherapy and allodepletion. 1523 69

Improving survival rates following pediatric bone marrow transplantation (BMT) will likely result in greater numbers of children progressing to end-stage renal disease (ESRD) because of prior chemotherapy, irradiation, sepsis, and exposure to nephrotoxic agents. Renal transplantation remains the treatment of choice for ESRD; however, the safety of renal transplantation in this unique population is not well established. We report our experience with living related renal transplantation in three pediatric patients with ESRD following prior BMT. Two patients with neuroblastoma and ESRD because of BMT nephropathy, and one patient with Schimke immuno-osseous dysplasia and ESRD because of immune complex mediated glomerulonephritis and nephrotic syndrome. Age at time of BMT ranged from 2 to 7 yr. All patients had stable bone marrow function prior to renal transplantation. Age at renal transplant ranged from 8 to 14 yr. All three patients have been managed with conventional immunosuppression, as no patient received a kidney and BMT from the same donor source. These patients are currently 7 months to 6 yr status post-living related transplant. All have functioning bone marrow and kidney transplants, with serum creatinine levels ranging 0.6-1.2 mg/dL. There have been no episodes of rejection. One patient with a history of grade III skin and grade IV gastrointestinal-graft-vs.-host disease (GI-GVHD) prior to transplantation, had a mild flare of GI-GVHD (grade I) post-renal transplant and is currently asymptomatic. The incidence of opportunistic infection has been comparable with our pediatric renal transplant population without prior BMT. One patient was treated for basal cell carcinoma via wide local excision. Renal transplantation is an excellent option for the treatment of pediatric patients with ESRD following BMT. Short-term results in this small population show promising patient and graft survival, however long-term follow-up is needed. Pre-existing immune system impairment and bone marrow function should be taken into consideration when weighing different immunosuppressive agents for renal transplantation. Patients who have undergone renal transplantation following BMT are at high risk for opportunistic infections and malignancy, and need life-long medical surveillance.
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PMID:Successful renal transplantation following prior bone marrow transplantation in pediatric patients. 1536 89

We report the first case of Phialemonium obovatum fungemia with subsequent caseating granulomatas in the lung and Crohn disease-like involvement of the gastrointestinal tract in a bone marrow transplant recipient. This phaeoid fungus has been rarely described as an opportunistic infection in immunosuppressed patients. The patient was diagnosed with chronic myelogenous leukemia and underwent subsequent peripheral bone marrow transplant. After 6 months, he developed graft-versus-host disease of the skin and liver with fever and severe diarrhea. Fecal bacterial cultures and cytomegalovirus serologies were negative. Computed tomographic scan showed a peripheral pulmonary mass. A lung wedge biopsy of the lesion showed septate branching hyphae (4-5 microm in diameter) with terminal globular structures (10 microm in diameter). The hyphae were similar in width to that of an Aspergillus species but had a more moniliform appearance. Blood cultures grew a pure culture of P. obovatum. He was treated with amphotericin B and itraconazole for 6 months without remission of the diarrhea. Biopsies of the stomach, colon, and rectum showed granulomatous inflammation with marked crypt distortion simulating Crohn disease. In retrospect, the fungus was found to be resistant to both of the aforementioned drugs and susceptible to voriconazole and posaconazole. The gastrointestinal findings raise the possibility of further dissemination of a partially treated Phialemonium infection.
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PMID:Lung infection due to opportunistic fungus, Phialemonium obovatum, in a bone marrow transplant recipient: an emerging infection with fungemia and Crohn disease-like involvement of the gastrointestinal tract. 1608 58

Pneumocystis jiroveci pneumonia (PCP) has become a rare opportunistic infection due to the efficacy of prophylactic regimens. We conducted a 6-year retrospective study at our institution. A total of 13 cases of PCP were diagnosed among 519 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (2.5%). In three patients, PCP occurred within the first 5 months following HSCT. These severely immunocompromised patients were receiving prophylaxis and had concomitant aspergillosis that caused rapid death in two of them. In 10 other patients, PCP occurred a median of 14.5 months after HSCT. In all these patients, PCP prophylaxis had been discontinued, mainly because of the suspected bone-marrow toxicity of the prophylactic regimen. Median CD4+ T cell count was 131/microl at diagnosis. Seven of these 10 patients were receiving immunosuppressive therapy for chronic graft versus host disease and three had a relapse of their hematological malignancy. One patient died from PCP despite high doses of cotrimoxazole. We conclude that PCP is still occurring after allogeneic HSCT, mainly as a late complication in patients in whom PCP prophylaxis had been prematurely discontinued. Long-term PCP prophylaxis should be maintained in patients receiving immunosuppressive drugs, and in those with low CD4+ T cell counts or a relapse of their hematological malignancy.
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PMID:Occurrence of Pneumocystis jiroveci pneumonia after allogeneic stem cell transplantation: a 6-year retrospective study. 1615 23

Thrombocytopenia (TP) is a frequent complication after allogeneic stem cell transplantation (SCT) and regarded as a poor prognostic factor when assessed beyond day 100. However, little is known about the clinical significance of the platelet recovery pattern before chronic graft-versus-host disease (GVHD) develops. Eighty-five patients undergoing HLA-identical sibling SCT were stratified according to their platelet recovery pattern between day +30 and +90 and the transplant outcomes analyzed, along with the association of each component of the acute GVHD grading system. Fifteen patients (18%) were classified with persistent TP, 33 patients (39%) with unstable TP, and 37 patients (43%) as non-TP. Persistent TP, which was strongly associated with severe acute GVHD (P<0.001), exhibited the worst 2-year OS (P<0.0001) and highest NRM (P<0.0001) and opportunistic infection rates (P<0.0001). In multivariate analyses, the platelet recovery pattern was identified as an independent prognostic factor (P=0.02) together with the disease risk (P=0.02) in terms of OS, and the only independent prognostic factor in terms of NRM (P=0.005) and the incidence of infectious events (P<0.001). Persistent TP was strongly associated with the development of extensive chronic GVHD (P=0.03). The platelet recovery pattern between day +30 and +90 can be used to predict the prognosis of SCT recipients.
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PMID:Prognostic significance of platelet recovery pattern after allogeneic HLA-identical sibling transplantation and its association with severe acute GVHD. 1625 33

Transforming growth factor beta (TGF-beta) family is recognised as one of the major regulators of immune response. Increased synthesis of TGF-beta has been linked to immune defects associated with malignancy and autoimmune disorders, to susceptibility to opportunistic infection, and to fibrotic disease. It is widely believed that this factor is related to the development of two main features of chronic graft dysfunction and rejection, namely fibrosis and atherosclerosis. Studies of haematopoietic pathologies involving TGF-beta have provided an important evidence of its key role in regulation of haematopoiesis. Recent studies have indicated that TGF-beta may be a significant mediator of the profound and prolonged immunosuppression found during graft versus host disease (GVHD) after allogeneic haematopoietic stem cell transplantation. It has also been linked with scleroderma-like features often described in chronic GVHD. Moreover, particular TGF-beta polymorphisms may be prognostic factors in predicting a post-transplant outcome.
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PMID:[Current review on the role of transforming growth factor beta (TGF-beta) in some pathological disorders]. 1652 65

Acute and chronic graft-versus-host disease (GVHD) are major complications after allogeneic hematopoietic stem cell transplantation. Systemic corticosteroid is the first line of therapy but only half of the patients will respond. The management of steroid-refractory or steroid-dependent GVHD is challenging. Intensification of immunosuppression has been the main strategy but the response rate is not satisfactory. Furthermore, the incidence of treatment-related toxicity and opportunistic infection is unacceptably high. Extracorporel photopheresis (ECP) has been used in the management of refractory GVHD. Retrospective analysis of the experience in adult patients showed activity in both acute and chronic GVHD. The procedure was well tolerated with minimal changes in the hematologic and biochemical parameters. However the machine currently approved is designed for patients over 40 kg of body weight. Significant fluid shift and venous access are major concerns when ECP is performed in children. Various modifications of the ECP procedure have been tried to manage patients with low body weight. Experience with ECP in children is limited but preliminary data also showed favorable response in children with resistant GVHD. Further investigations are needed to refine the optimal schedule, duration, and treatment technique for pediatric patients.
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PMID:Extracorporeal photopheresis in children with graft-versus-host disease. 1661 29

Hematopoietic stem cell transplantation (HSCT) is being used to treat a wide spectrum of clinical disorders but opportunistic infection remains an important factor determining outcomes for these patients. Nontuberculous mycobacterial (NTM) infections are being reported more frequently in HSCT recipients and the incidence of NTM infections in adult recipients is reported to be 0.4%-4.9%. However, the incidence and severity of NTM infections are less well described in pediatric HSCT recipients. Centers for Disease Control and Prevention guidelines were used to define definite and probable NTM infection among 132 children undergoing 169 HSCT between January 2000 and December 2004 at our institution. NTM infection was diagnosed in 5 of 132 pediatric recipients (3.8%). There were no NTM infections diagnosed in the autologous HSCT recipients and the incidence of NTM in allogeneic HSCT recipients was 6.4% (95% confidence interval, 0.8-11.9). The mean age of the HSCT recipients who developed NTM infections was 8 years (range, 2-19 years); 3 were male and 2 were female. Four conditioning regimens included alemtuzumab and 3 had antithymocyte globulin. Of the 5 patients with NTM infections, 2 met the criteria for definite infection and 3 for probable infection. Of the 2 patients with definite NTM infection, 1 had disseminated disease with Mycobacterium avium complex and the other had Mycobacterium chelonae catheter-related bloodstream infection. The probable NTM infections were 1 skin infection with Mycobacterium kansasii and 2 lower respiratory tract infections with M avium complex. Median time to NTM infection was 115 days (range, 14-269 days) after HSCT. Two patients had graft-versus-host disease at the time of NTM infection. All 5 patients received 3-4 antimycobacterial drugs and all NTM infections resolved. In summary, the incidence of NTM infection in pediatric HSCT recipients appears similar to that described in adult HSCT recipients and the outcome appears to be excellent with the proper antibiotic therapy. The increased use of anti-T cell antibodies appears to be associated with an increased risk of NTM infections in pediatric HSCT recipients. Multicenter studies are needed to identify the risk factors, early diagnostic criteria, and optimal therapy.
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PMID:A low incidence of nontuberculous mycobacterial infections in pediatric hematopoietic stem cell transplantation recipients. 1708 12


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