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Host Disease (host + disease)
Kinds of Host Disease Selected AbstractsHigh risk of hepatitis B-virus reactivation after hematopoietic cell transplantation in hepatitis B core antibody-positive patientsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2009Kosei Matsue Abstract We investigated the serological changes in hepatitis B virus (HBV)-related markers in 55 and 26 hepatitis B surface antigen (HBsAg)-negative patients undergoing allogeneic and autologous stem cell transplantation, respectively, over the past 4 yr. Five of the 17 allogeneic and one of the five autologous patients with pretransplant anti-hepatitis B core antigen antibodies (anti-HBc) were HBsAg-positive after transplantation, whereas none of the patients negative for anti-HBc were HBsAg-positive in both groups. All patients who became HBsAg-positive received steroid-containing immunosuppressive therapy for chronic graft versus host disease (GVHD) or myeloma. Four of the six patients developed flare of HBV hepatitis, and two patients did not. One patient developed fulminant hepatitis treated with lamivudine and plasma exchange. Other five patients received entecavir from the detection of HBsAg. Although HBV-DNA levels became below the limit of detection in all patients, HBsAg positivity remained in three patients after 6 months of treatment. We concluded that anti-HBc positivity is a risk factor for reactivation of HBV after both autologous and allogeneic transplantation, and HBV-related markers should be monitored regularly in these patients. We also stress the efficacy of pre-emptive use of antiviral agents in controlling HBV replication and limiting hepatic injury due to reactivation of HBV in these patients. [source] Quantitative assessment of WT1 gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009Anna Candoni Abstract Introduction:,WT1 overexpression is described in several oncological diseases including acute myeloid leukemia (AML). Quantification of WT1 in bone marrow samples may be useful as a marker of minimal residual disease (MRD) and may predict the relapse of AML after allogeneic hematopoietic stem cell transplant (HSCT). Methods and results:, The quantitative expression of WT1 was measured in 38 AML patients (16 males and 22 females) at diagnosis, at the time of transplant and after the allogeneic HSCT (at precise time points). All cases showed high WT1 expression levels at diagnosis with a mean of 4189 (SD 3325) and a median of 3495 (range 454,13923) copies WT1/104Abl. At transplant, 25 patients (66%) were in complete cytologic remission (CcR) and 13 (34%) had refractory or relapsed AML. Bone marrow samples from patients transplanted in CcR showed significantly lower WT1 expression levels during HSCT compared with the samples from patients with a relapsed or refractory AML (P = 0.004). After HSCT, a rapid decline in WT1 expression levels was observed in all patients who attained or maintained a condition of CcR. Six of 38 patients (13%) relapsed after HSCT and all of them had an increase in WT1 expression at/or before relapse. Five of these six patients died of leukemia and one was successfully reinduced with donor lymphocyte infusion (DLI) + chemotherapy with a rapid reduction of WT1 levels. Besides, we found a complete concordance between WT1 expression levels and other disease markers (when available). Conclusions:, In our experience, there was a complete concordance between WT1 expression levels (measured by quantitative RT-PCR at precise time points) and status of AML before and after allogeneic HSCT. WT1 may be useful as a non-specific leukemia marker for monitoring MRD and as a predictor of AML clinical relapse. Based on these results, cases with increase of WT1 levels after HSCT and without graft vs. host disease may be candidate to discontinuation of immunosuppression and/or DLI therapy. [source] Parvovirus B19 infection as trigger of graft vs. host diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2008Gerhard Behre No abstract is available for this article. [source] Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor regionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2006Kiyoshi Kitano Abstract:, Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis. [source] Favourable outcome for patients with myeloid disorders treated with fludarabine,melphalan reduced-intensity conditioning and allogeneic bone marrow stem cell transplantation without the use of T-lymphocyte-depleting antibodiesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2004R. K. Malladi Abstract:, We report the use of reduced-intensity conditioning (RIC)-matched sibling allogeneic bone marrow stem cell transplantation as a method of establishing a graft-vs.-leukaemia (GvL) effect against myeloid disorders using a fludarabine,melphalan protocol without the use of T-lymphocyte-depleting antibodies. The 16 patients in this group had predominantly poor-risk acute myeloid leukaemia (AML) (n = 10), AML/myelodysplasia (MDS) (n = 2) and MDS (n = 4). All but one patient achieved full haematopoietic engraftment. Thirteen of 16 patients are alive and in continued complete remission on completion of this study with a median follow-up of 426 d (range 83,1524). The actuarial 4 yr disease-free and overall survival is 79% for both. Only one patient relapsed following transplant, giving a relapse rate of 6% during the study period. The treatment-related mortality was 13% (n = 2). Overall, acute graft-vs.-host disease (GvHD) occurred in 53% (8/15), with acute GvHD grade II or above occurring in 47% (7/15). In the 13 evaluable patients, chronic GvHD occurred in 46% (6/13), with this being extensive in three patients. These results suggest that a GvL effect can be delivered against poor-risk myeloid disorders with a low non-relapse mortality using this fludarabine,melphalan RIC protocol. [source] Kinetics of stem cell engraftment and clearance of leukaemia cells after allogeneic stem cell transplantation with reduced intensity conditioning in chronic myeloid leukaemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2002Karl-Anton Kreuzer Abstract: It is hypothesised that an effective graft-vs.-leukaemia reaction contributes substantially to the therapeutic effect of reduced intensity conditioning stem cell transplantation in chronic myeloid leukaemia. However, kinetic data on eradication of leukaemia cells and stem cell engraftement which could support this assumption are lacking . Thus, we investigated bcr/abl fusion transcripts and haematopoietic chimerism in 14 patients undergoing such a transplantation protocol. Ten of them obtained a complete molecular remission, and two patients achieved haematologic remissions but remained bcr/abl positive. Weekly determinations of bcr/abl transcript numbers by qualitative and quantitative polymerase chain reaction and donor chimerism revealed that 10 responders cleared bcr/abl positive cells from the peripheral blood within a median of 9 wk (range 3,22 wk). The close relation (P = 0.0075) between the firstoccurrence of graft-vs.-host disease and the complete clearance ofbcr/abl positive blood cells argues in favour of an effective graft-vs.-leukaemia reaction. [source] Regulatory T cells for the prevention of graft- versus -host disease: Professionals defeat amateursEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2009Matthias Edinger Abstract CD4+CD25+ Treg are pivotal for the maintenance of self-tolerance and the adoptive transfer of Treg is envisaged for the treatment of autoimmune diseases and the induction of tolerance after allogeneic organ or stem cell transplantation. Owing to the paucity of natural Treg in peripheral blood, isolation of Treg for therapeutic purposes is cumbersome and not easily translatable into clinical trials. To circumvent such hurdles, many groups are exploring the de novo induction of Treg from conventional T cells for potential clinical applications. In this issue of the European Journal of Immunology, a paper examines the therapeutic efficacy of natural and induced Treg in a model of graft- versus -host disease and report that induced Treg rapidly lose their Treg features in an allogeneic environment and are unable to prevent disease. Thus, the stability of induced Treg is of major concern as discussed in this Commentary. [source] Activated NKT cells increase dendritic cell migration and enhance CD8+ T cell responses in the skinEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2006Anton Abstract Activated NKT cells produce cytokines such as IL-4 and IFN-, that function locally to influence the strength and functional development of antigen-specific T cells. Here we identify an alternative mechanism by which NKT cells influence the strength of T cell responses: through modulation of peripheral dendritic cell (DC) trafficking. NKT cell activation with ,-galactosylceramide induced high systemic levels of TNF-, that mediated increased DC migration from skin to draining lymph nodes. This increased DC trafficking led to a threefold increase in effector T cell priming and in the immune response elicited to antigen challenge when ,-galactosylceramide was given at the time of immunization of the skin. These studies provide important implications for the use of NKT cell activation strategies to manipulate T cell-mediated responses including responses to cutaneous tumors and graft vs. host disease. [source] Antifungal prophylaxis in adult stem cell transplantation and haematological malignancyINTERNAL MEDICINE JOURNAL, Issue 6b 2008M. A. Slavin Abstract Antifungal prophylaxis can be recommended in patients undergoing induction chemotherapy for acute myeloid leukemia and treatment for grade 2 or greater or chronic extensive graft versus host disease. The evidence for prophylaxis is less clear in other clinical settings although certain groups such as patients with prolonged neutropenia after stem cell transplants using bone marrow or cord blood sources and with impaired cell mediated immunity secondary to treatments such as Alemtuzumab are at high risk. The decision to use prophylaxis and which agent to use will be influenced by effectiveness, number needed to treat and the likelihood of toxicity and drug interactions. The availability of rapid diagnostic tests for fungal infection and institutional epidemiology will also influence the need for and choice of prophylaxis. Whilst prophylaxis can be beneficial, it may impede the ability to make a rapid diagnosis of fungal infection by reducing the yield of diagnostic tests and change the epidemiology of fungal infection. As non-culture based diagnostic tests are refined and become more available there may be a shift from prophylaxis to early diagnosis and treatment. [source] Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2009FNASC, FRAS(LOND.), Virendra N. Sehgal MD Paraneoplastic pemphigus is the term used for an exclusive subset of pemphigus. The clinical lesions may resemble pemphigus, pemphigoid, erythema multiforme, graft-vs.-host disease, or lichen planus. A common denominator in all patients is the concomitant occurrence of either occult or confirmed systemic neoplasm. It is imperative to confirm the diagnosis through microscopy, where intraepidermal suprabasal cleavage, epidermal acantholysis, dyskeratotic keratinocytes and vacuolar changes in the basal epidermis, interfacial dermatitis, and epidermal exocytosis can be seen. Furthermore, the deposition of immunoglobulin G (IgG) and complement in the epidermal intercellular spaces, detected by direct and/or indirect immunofluorescence, is equally crucial for confirming the diagnosis. [source] Rituximab: Applications in dermatologyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2006Mitra M. Fatourechi Rituximab is a chimeric anti-CD20 monoclonal antibody which has been used extensively for B-lymphocytic malignancies. In addition, applications for autoimmune diseases have emerged in recent years. Case reports support the use of rituximab in certain dermatologic conditions, including paraneoplastic pemphigus, pemphigus vulgaris, graft versus host disease, and cutaneous B-cell malignancies. Clinical trials are lacking and would be an appropriate next step. [source] Lichenoid nail changes as sole external manifestation of graft vs. host diseaseINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2002Sara Isabel Palencia MD A 56-year-old-man who had refractory anemia with an excess of blasts underwent an allogeneic peripheral blood stem cell transplantation (PBSCT) from his brother after preparation with melphalan and fludarabin. He received GvHD (graft-vs.-host disease) prophylaxis with cyclosporine from day ,1 at a daily dose of 5 mg/kg of body weight. The daily dosage was tapered gradually from day +20. On post-PBSCT day 68 he developed acute cutaneous GvHD grade 3 and acute gastrointestinal GvHD grade 2,3, which was resolved with a daily dose of 1 mg/kg of body weight of prednisone. The patient was discharged in good clinical condition and without signs of GvHD, and he started tapering his immunosuppressive treatment. By day 160 he developed oral lichen planus-like changes, with several reticulate white lesions on the oral mucosa. A biopsy specimen was microscopically consistent with lichenoid GvHD (Fig. 1). By day 150 after PBSCT, when he was being treated with CsA 100 mg once daily and prednisone 10 mg once daily, his fingernails started to grow abnormally and gradually became dystrophic and painful. Two months later his toenails became similarly affected. Although affecting all finger and toe nails, the lesions were especially important in both thumbs. Physical examination revealed multiple findings on his nails (Fig. 2): thickening, fragility, onycholysis, longitudinal striations, and even pterygium. The micological cultures were negative. A biopsy specimen showed an sparse papillary dermis lymphoid infiltrate with focal exocytosis and presence of isolated multiple necrotic keratinocytes (Fig. 3). These findings were interpreted as a lichenoid GvHD with oral and nail involvement. The patient did not have other associated cutaneous lesions. He did not develop signs or symptoms consistent with hepatic GvHD. In May 2000 thalidomide was added to the immunosuppressive therapy, at a daily dose from 100 to 300 mg according to tolerance (constipation, sedation, ,). The lesions on the oral mucous showed a substantial improvement, but the nail changes remained more or less stable. Thalidomide was discontinued after 7 months because the patient displayed numbness and tingling in the hands and feet consistent with a peripheral neuropathy. Twenty days later he stopped taking thalidomide and the oral lichenoid lesions worsened, resulting in difficulty in eating. He also developed periungueal erythema, swelling and intense pain after minimal trauma. The daily dose of prednisone increased to 20,30 mg with moderate improvement. However, the dose could not be increased because of the secondary immunosuppressive effects. Twenty-three months post-PBSCT the patient remains with intense oral and nail lichenoid lesions. Figure Figure 1 . Oral mucosa with a lichenoid hiperplasia and a band-like lymphoid infiltrate. Note the basal lymphocytosis with isolated necrotic keratinocytes Figure 2. Lichenoid graft-vs.-host disease showing marked nail involvement with a ridge in the midline Figure 3. Panoramic view of the nail epithelium. Dermal lymphocytes with basal exocytosis and apoptotic keratinocytes (arrow) are evident [source] Adult stem cell plasticity: will engineered tissues be rejected?INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2004Te-Chao Fang Summary The dogma that adult tissue-specific stem cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that adult stem cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic stem cells, for example, could be exploited to generate and perhaps deliver cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated cells bearing the donor marker is indicative of a switch in phenotype of a stem cell or a member of a transit amplifying population or of a differentiated cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model systems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of cell therapy, yet immune rejection will present challenges. Graft- vs. -host disease will continue to present problems, although this may be avoided if the cells were derived from the recipient or they were tolerized. Despite great expectations for cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype. [source] Selected Stro-1-enriched bone marrow stromal cells display a major suppressive effect on lymphocyte proliferationINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2009A. NASEF Summary Mesenchymal stem cells (MSCs) have an immunosuppressive effect and can inhibit the proliferation of alloreactive T cells in vitro and in vivo. Cotransplantation of MSCs and hematopoietic stem cells (HSCs) from HLA-identical siblings has been shown to reduce the incidence of acute graft- vs.-host disease. MSCs are heterogeneous and data on the inhibitory effects of different MSC subsets are lacking. The antigen Stro1 is a marker for a pure primitive MSC subset. We investigated whether Stro-1-enriched induce a more significant suppressive effect on lymphocytes in a mixed lymphocyte reaction (MLR), and whether this action is related to a specific gene expression profile in Stro-1-enriched compared to other MSCs. We demonstrated that the Stro-1-enriched population elicits a significantly more profound dose-dependent inhibition of lymphocyte proliferation in a MLR than MSCs. One thousand expanded Stro-1-enriched induced an inhibitory effect comparable to that of 10 times as many MSCs. Inhibition by Stro-1-enriched was more significant in contact-dependent cultures than in noncontact-dependant cultures at higher ratio. The Stro-1-enriched inhibitory effect in both culture types was linked to increased gene expression for soluble inhibitory factors such as interleukin-8 (IL-8), leukemia inhibitory factor (LIF), indoleamine oxidase (IDO), human leukocyte antigen-G (HLA-G), and vascular cell adhesion molecule (VCAM1). However, tumor growth factor-,1 (TGF-,) and IL-10 were only up-regulated in contact-dependant cultures. These results may support using a purified Stro-1-enriched population to augment the suppressive effect in allogeneic transplantation. [source] HLA-haploidentical nonmyeloablative stem cell transplantation: induction to tolerance without passing through mixed chimaerismINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2005K. IKEGAME Summary There are few reports of unmanipulated HLA-haploidentical nonmyeloablative stem cell transplantation (NST) using only pharmacological acute graft- vs. -host disease (GVHD) prophylaxis. We present here a successful case of unmanipulated HLA-haploidentical NST for mediastinal large B cell lymphoma that was resistant to autologous peripheral blood stem cell transplantation (PBSCT). The conditioning regimen consisted of fludarabine, busulfan and rabbit anti-T-lymphocyte globulin (ATG) in addition to rituximab. GVHD prophylaxis was performed using tacrolimus and methylprednisolone 1 mg/kg. The patient had rapid engraftment, with 100% donor chimaerism in the lineages of both T cells and granulocytes on day +12, but developed no GVHD clinically. The patient is still in complete remission past day +1020, with no sign of chronic GVHD without receiving immunosuppressive agents. HLA-haploidentical NST may be performed without utilizing mixed chimaerism. [source] Granulocyte colony-stimulating factor produces a decrease in IFN, and increase in IL-4 when administrated to healthy donorsJOURNAL OF CLINICAL APHERESIS, Issue 4 2010Octavio Rodríguez-Cortés Abstract Hematopoietic stem cells transplantation (HSCT) is the leading curative therapy for a variety of hematological and hereditary diseases; however, graft versus host disease (GVHD), an immunologic phenomenon that is favored by Th1 cytokines and cytotoxic cells from donors, is present frequently and is one of the most important causes of transplant related mortality. Peripheral blood HSCT is the preferred source of stem cells in almost 100% of the cases of autologous HSCT and in 70% of allogeneic transplants. The best mobilizing agent to get the stem cells out from the bone marrow is the Granulocyte-Colony Stimulating Factor (G-CSF). In this work, our main objective was to study a possible correlation between the graft cell dose and the patient's clinical outcome. We evaluated the immunologic changes produced by G-CSF in the lymphocyte and cytokine profiles in allogeneic HSC donors. HSC from twelve donors were mobilized with G-CSF at 16 ,g/kg/day, for 5 days. Basal Peripheral Blood (BPB), Mobilized Peripheral Blood (MPB), and aphaeresis mononuclear cells (G-MNC) samples were taken from all donors. Using flow cytometry, we quantified CD19+, CD3+, CD3+CD4+, CD3+CD8+, NK, NKT, DC1, and DC2 cells. Cytokines were determined by ELISA in culture supernatants. CD19+ (p = 0.001), DC1 (p < 0.002) and DC2 (p < 0.001) cells were increased in MPB with respect to BPB. An increase in Th2 cytokines such as (IL-4) and a decrease in Th1 cytokines (IFN,, IL-2) were also found in MPB samples. In conclusion, Th1 and Th2 cytokines are relevant in predicting the clinical outcome after allogeneic peripheral blood HSCT. J. Clin. Apheresis 25:181,187, 2010. © 2010 Wiley-Liss, Inc. [source] The Italian registry of pediatric therapeutic apheresis: A report on activity during 2005JOURNAL OF CLINICAL APHERESIS, Issue 1 2009Giustina De Silvestro Abstract The results of the 2005 Survey of the Italian Society for Apheresis and Cell Manipulation (SIdEM) reporting on the pediatric procedures carried out in 18 Italian Apheresis Units are presented here. Utilizing a standardized questionnaire, the survey collected data on techniques, types of blood separators, clinical indications, and adverse events. A total of 1,693 apheresis procedures were carried out in 355 pediatric patients: 219 plasma-exchange, 291 peripheral blood stem cell collections, 791 extracorporeal photochemotherapy (ECP), 265 LDL-apheresis, 71 erythro-exchange, 9 cytoreductive apheresis, 47 immunoadsorption sessions. Adverse events were registered in 94 procedures (5.6%), most of which of mild entity, e.g., insufficient flow rate (50.0%) and symptomatic hypocalcemia (24.4%). Our data indicate that all types of apheresis procedures can be safely carried out in children. ECP, utilized primarily for the treatment of graft versus host disease (GvHD) and rejection of solid organ transplantation, are burgeoning procedures in pediatric patients, whereas plasma exchange, which is a common treatment in adults, is infrequently utilized in pediatric medicine. J. Clin. Apheresis, 2009. © 2008 Wiley-Liss, Inc. [source] Extracorporeal photopheresis reduces the number of mononuclear cells that produce pro-inflammatory cytokines, when tested ex-vivoJOURNAL OF CLINICAL APHERESIS, Issue 4 2002John Bladon Abstract Extracorporeal photopheresis (ECP) has been shown to be clinically effective in the treatment of many T cell,mediated conditions. ECP's mechanism of action includes the induction of apoptosis and the release of pro-inflammatory cytokines. Recently, we have observed early lymphoid apoptosis, detectable immediately post ECP. We were interested to determine what influence ECP has on pro-inflammatory cytokine secretion at this early pre-infusion stage. Samples from 6 cutaneous T cell lymphoma (CTCL) and 5 graft versus host disease (GvHD) patients were taken pre ECP and immediately post ECP, prior to re-infusion. Following separation, the PBMCs were added to a cell culture medium and stimulated with PMA, Ionomycin, and Brefeldin A for 6 hours. Using flow cytometry, intracellular cytokine expression of IFN, and TNF, was determined in the T cell population. The monocytes were evaluated for IL6, IFN,, IL12, and TNF,. For both patient groups, the number of IFN,-expressing T cells fell significantly at re-infusion, whilst both T cell- and monocyte-expressing TNF, levels were reduced at re-infusion. All other cytokines tested showed no significant change post ECP. For GvHD, pro-inflammatory cytokines have a pathological role. Their down-regulation may have a direct clinical benefit. However, the reduction in the number of IFN,- and TNF,-expressing mononuclear cells means, at this early stage, it is unlikely that these cytokines assist in the removal of the malignant Th2 cells present in CTCL. J. Clin. Apheresis 17:177,182, 2002. © 2002 Wiley-Liss, Inc. [source] Hematologic aspects of myeloablative therapy and bone marrow transplantationJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2005Roger S. Riley Abstract The transplantation of bone marrow cells or isolated hematopoietic stem cells from the bone marrow or peripheral blood is a widely utilized form of therapy for patients with incurable diseases of the hematopoietic and immune systems. Successful engraftment of the transplanted stem cells in an adequately prepared recipient normally leads to bone marrow reconstitution over a period of several weeks, accompanied by more gradual reconstitution of the immune system. Since the recipient is profoundly ill during the initial treatment period, laboratory data is critical for monitoring engraftment, detecting residual/recurrent disease, and identifying problems that may delay bone marrow reconstitution or lead to other medical complications. Accurate blood cell counts are imperative, and most bone marrow transplantation patients undergo periodic monitoring with bone marrow aspirates and biopsies with cytogenetic, molecular, and multiparametric flow cytometric studies. The potential complications of bone marrow transplantation include engraftment failure and delayed engraftment, infection, residual bone marrow disease, acute and chronic graft versus host disease, myelofibrosis, therapy-related acute leukemia, post-transplant lympho-proliferative disorders, and toxic myelopathy. J. Clin. Lab. Anal. 19:47,79, 2005. © 2005 Wiley-Liss, Inc. [source] Comparison of HPV infection, p53 mutation and allelic losses in post-transplant and non-posttransplant oral squamous cell carcinomasJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2002L. Zhang Abstract Background:, Oral squamous cell carcinoma (SCC) is increasingly found in transplant recipients, although little is known of the natural history of the disease or the mechanism underlying this increase. Methods:, In this article we describe the history of development of 5 oral post-transplant SCCs (PSCCs) and compare their genetic profiles to 34 non-posttransplant SCCs (NPSCCs). Results:, Of the five patients with PSCCs, 3 had bone marrow transplants and two, kidney. All three PSCCs from bone marrow recipients were preceded locally by graft-vs.-host disease (GVHD). Two of the GVHD were biopsied and demonstrated dysplasia. Similar frequencies of loss of heterozygosity (LOH) occurred in PSCCs and NPSCCs at 3p, 9p, 17p and 8p, with lower frequencies in PSCCs at 4q (39% vs. 0%), 11q (53% vs. 20%) and 13q (45% vs. 20%), although the latter were not significantly different. Only 1 PSCC had a p53 mutation, compared to historical values of 40,60% for NPSCC. Interestingly, human papillomavirus (HPV) DNA was detected in 3 (60%) PSCCs, in comparison to only 4 (12%) of the 34 NPSCCs (P = 0.0346). Conclusions:, Dysplasia in oral GVHD may be a strong indicator of cancer risk and should not be regarded as reactive changes to lichenoid mucosites. The low level of p53 mutation and increased HPV infection support the involvement of HPV in the development of PSCC, while the similarity in LOH patterns suggests that other aspects of carcinogenesis may be comparable in these two types of SCCs. [source] Bone marrow transplantation for ,-thalassaemia major by an HLA-mismatched parentJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 3 2002CF Li Abstract: A six-year-old boy was diagnosed with ,-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 × 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for ,-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD. [source] Recipient and donor factors influence the incidence of graft-vs.-host disease in liver transplant patientsLIVER TRANSPLANTATION, Issue 4 2007Edie Y. Chan Acute cellular graft-vs.-host disease (GVHD) following liver transplantation has an incidence of 1 to 2% and a mortality rate of 85%. Our aim was to identify a patient population at high risk for developing GVHD using a large clinical database to study both recipient and donor factors. We compared our liver transplant patients who developed GVHD to those that did not for recipient and donor factors and combinations of factors. For 2003,2004 we had 205 first-time liver transplant patients surviving >30 days. From this group, 4 (1.9%) developed GVHD. Compared to the control group, there were no significant differences in recipient age, recipient gender, donor age, donor gender, total ischemia time, donor-recipient human leukocyte antigen (HLA) mismatch, or donor-recipient age difference. Percentages of liver disease etiologies among the patients who developed GVHD were as follows: 16% (1/6) autoimmune hepatitis (AIH) (P = 0.003), 5.6% (3/54) alcoholic liver disease (ALD) (P = 0.057), and 7.1% (3/42) hepatocellular carcinoma (HCC) (P = 0.026). The incidence of GVHD in patients with glucose intolerance (either Type I or Type II diabetes mellitus [DM]) was significant (P = 0.022). Focusing on patients only with high-risk factors for GVHD during the years 2003,2005, we had 19 such patients. Four of these high-risk patients developed GVHD. Three of these 4 patients had received a donor liver with steatosis of degree ,mild compared to only 2 of the 15 high-risk patients who did not develop GVHD (P = 0.037). In conclusion, we have identified liver transplant patients with AIH or the combination of ALD, HCC, and glucose intolerance who receive a steatotic donor liver as being at high risk for developing GVHD. Liver Transpl 13:516,522, 2007. © 2007 AASLD. [source] Synergistic effects of RAD and Neoral in inhibition of host-vs.-graft and graft-vs.-host immune responses in rat small-bowel transplantationMICROSURGERY, Issue 5 2003Stéphane Johnson M.Sc. The combined effects of RAD and Neoral were tested in a rat orthotopic small-bowel transplantation model. Seven groups (n = 6) were involved in this study, and each one was included in three rejection models for the evaluation of host-vs.-graft disease (HVG) (LBN-F1 to LEW), graft-vs.-host disease (GVH) (LEW to LBN-F1), and combined HVG and GVH immune responses (BN to LEW). Both drugs were administered orally throughout the study. Low doses of RAD (1.0,2.5 mg/kg/day) combined with Neoral (2.0,5.0 mg/kg/day) produced strong synergistic effects in the prolongation of small-bowel graft survival in HVG (combination index, CI = 0.095, 0.1212), GVH (CI = 0.027, 0.020), and combined HVG and GVH immune responses (CI = 0.070, 0.301). The combination therapy of RAD and Neoral produces a strong synergistic effect toward the inhibition of HVG, GVH, and combined HVG and GVH immune responses in a rat small-bowel transplantation model. © 2003 Wiley-Liss, Inc. MICROSURGERY 23:476,482 2003 [source] An anaphylactic reaction to blood supplied from patient's motherACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2002Y. Nakaigawa We present the case of a 4-year-old girl who developed anaphylactic shock during general anesthesia. Symptoms appeared 80 min into the operation and may have been an immediate allergic reaction to the transfused blood supplied from the child's mother based on the clinical signs, the decrease of components of complements and the elevated concentrations of histamine and tryptase. The blood type was the same and antibody screening test and crossmatch was negative. The blood was irradiated and we used a white cell-reduction filter. This patient possibly has antibodies to her mother's plasma and this type of reaction cannot be prevented by these routine methods. It is reported that the risk of transfusion associated graft-vs.-host disease is high when a patient receives blood from a closely related donor. However, there are, no reports of anaphylactic reactions to blood supplied from mother to child. We suggest that there is a potential for anaphylactic reaction as well as transfusion associated graft-vs.-host disease when a child patient receives blood from the mother. [source] Gastric contents in pediatric patients following bone marrow transplantationPEDIATRIC ANESTHESIA, Issue 7 2010GHASSAN WAHBEH MD Summary Background:, Graft versus host disease (GVHD) of the gut is thought to delay gastric emptying and so may increase the risk of aspirating retained contents while under anesthesia. Knowing that gastric emptying is delayed in patients with GVHD might lead one to choose to intubate the trachea for all patients with suspected GVHD, who present for diagnostic esophagogastricduodenoscopy (EGD). We are not aware of published data that gives specific guidance as to the need for intubation in the pediatric bone marrow or stem cell transplantation (BMT) population. This review was intended to evaluate the gastric contents (pH and volume) in this group of patients, to provide anesthesiologists with data that would inform their decisions about airway management for these patients. Methods:, Retrospective chart review of patients ,19 years of age undergoing EGD between 2004 and 2006. Gastric content volume and pH were measured in addition to underlying disease state and treatment. We compared BMT patients with suspected GVHD to nontransplant patients with other underlying gastrointestinal conditions. Results:, Data were obtained for 77 patients post-BMT undergoing EGD, including 40 patients whose biopsies and endoscopic findings were positive for GVHD, and 37 patients with no demonstrable GVHD. Records of 144 non-BMT patients undergoing EGD within the same study period were also reviewed. Conclusion:, Patients in the BMT group overall did not have higher volumes when compared to non-BMT patients. A secondary comparison of BMT patients who were found to have GVHD vs BMT patients without GVHD suggests that gastric content volume may be elevated with GVHD. Patients in the BMT group had statistically significantly higher gastric pH than patients in the non-BMT group. It is possible that the higher gastric volume in the GVHD-positive group could put them at slightly higher risk for aspiration, but the severity of any pneumonitis, should aspiration occur, might be mitigated, by the tendency toward a higher gastric pH in the BMT patients. [source] Hepatitic pattern of graft versus host disease in childrenPEDIATRIC BLOOD & CANCER, Issue 5 2007Héctor Melín-Aldana MD Abstract Background Liver involvement by graft-versus-host disease (GVHD) is characterized histologically by bile duct damage, which may be severe. A different pattern, "hepatitic GVHD," has been described in adult patients. This pattern also shows marked lobular hepatitis and hepatocellular damage. We report the development of hepatitic GVHD in six pediatric patients. Procedure Clinical information and histologic features of liver biopsy samples were retrospectively reviewed. Results Patients' ages ranged from 3 to 11 years. Underlying diagnosis, pre-transplant conditioning and GVHD prophylaxis varied. Peripheral blood stem cells were the source of the allograft in four patients, matched sibling in one, and matched-unrelated donor in one. Hepatic GVHD was detected between 149 and 310 days post-transplant. Prior acute GVHD had developed in two patients, and involved the skin and/or gastrointestinal tract. No patients had significant ductopenia. Only one patient had significant lymphocytic infiltration of bile ducts (ductitis). Bile duct epithelial damage and significant portal/periportal inflammation were present in all patients. Lobular necro-inflammation was present in five patients. Five patients improved with immunosuppression and one died with progressive GVHD. Conclusions This series focuses on hepatitic GVHD in pediatric patients. Clinical and histologic patterns are similar to what has been described in adults. Specific etiology and pathogenesis of this entity remain unclear. Pediatr Blood Cancer 2007;49:727,730. © 2006 Wiley-Liss, Inc. [source] Clinical outcomes and graft characteristics in pediatric matched sibling donor transplants using granulocyte colony-stimulating factor-primed bone marrow and steady-state bone marrowPEDIATRIC TRANSPLANTATION, Issue 3 2007Kuang-Yueh Chiang Abstract:, Matched sibling donor (MSD) transplant is a life-saving procedure for children with various hematological malignancies and non-malignancies. Traditionally, steady-state bone marrow (S-BM) has been used as the source of stem cells. More recently, peripheral blood stem cell (PBSC) after granulocyte-colony stimulating factor (G-CSF) mobilization has gained popularity. Adult studies of G-CSF-primed BM (G-BM) have shown that it produces rapid white blood cell engraftment like PBSC, but with less chronic graft-vs.-host disease. No such study has been published in pediatric patients. We conducted a pilot clinical trial of G-BM for pediatric patients. Ten patients were enrolled and were compared to a contemporaneous group of 12 patients who received S-BM. Patients in the G-BM group received a higher dose of total nucleated cells/kg (7.01 vs. 3.76 × 108, p = 0.0009), higher granulocyte,macrophage colony-forming units (CFU-GM)/kg (7.19 vs. 3.53 × 105, p = 0.01) and had shorter inpatient length of stay (28 vs. 40 days, p = 0.04). The engraftment, transfusion requirement and disease-free survival between the two groups were similar. We concluded that G-BM should be considered as an alternative graft source to S-BM, with the benefits of larger graft cell dose, higher CFU-GM dose and shorter length of stay. [source] Atypical skin graft-vs.-host disease following bone marrow transplantation in an infantPEDIATRIC TRANSPLANTATION, Issue 2 2007B. Kuskonmaz Abstract:, Herein, we describe an unusual presentation of acute graft versus host disease (GVHD) mimicking contact dermatitis in an infant who underwent 5/6 HLA-matched bone marrow transplantation (BMT) from his mother for malignant infantile osteopetrosis. The initial rash on day +32 simulated diaper rash, which progressed to a belt-shaped rash and then developed hyperkeratotic nodules on the hands. The acute GVHD was atypical and the course was progressive and fatal, with liver and gut involvement. This presentation of atypical initial skin involvement of acute GVHD may be useful for practicing clinicians in the BMT field who need to be aware of the early unusual signs of acute GVHD so that they can initiate prompt treatment. [source] Hematopoietic and immune recovery after allogeneic peripheral blood stem cell transplantation and bone marrow transplantation in a pediatric populationPEDIATRIC TRANSPLANTATION, Issue 4 2002Yoshihisa Nagatoshi Abstract: To compare the hematopoietic and immune recoveries after allogeneic transplantation with different cell sources, we analyzed the recovery patterns of blood components after allogeneic peripheral blood stem cell transplantation (PBSCT) in comparison with that after allogeneic bone marrow transplantation (BMT) in a pediatric population. Sixteen patients received PBSCT, and 24 received BMT between January, 1995 and March, 2000. The patients had acute lymphoblastic leukemia (ALL; n = 22), acute myelogenous leukemia (AML; n = 8), myelodysplastic syndrome (MDS; n = 3), or other diseases (n = 7). The median ages of patients in the PBSCT and BMT groups were 9 yr and 6 yr, respectively. Cyclosporin A (CsA) plus methotrexate or methylprednisolone was used as a graft-vs.-host disease (GvHD) prophylaxis regimen in the PBSCT group, whereas CsA alone or methotrexate alone was used in the BMT group. Circulating lymphocyte numbers and subpopulations determined by flow cytometric analysis were used as markers of immune recovery. In the PBSCT group, the median number of harvested CD34+ cells was 7.25 (range: 1.3,27.6) × 106/kg of the recipient's body weight, while the median number of harvested nucleated cells was 4.7 (range: 3.7,10.5) × 108/kg. All of the patients were engrafted. Myeloid engraftment occurred sooner after PBSCT than after BMT (median number of days to achieve absolute neutrophil counts (ANC) > 0.5 × 109/L; 11 and 15, respectively; p < 0.0001) and similar results were found for platelet engraftment (median number of days to achieve a platelet count of > 20 × 109/L; 12 and 21, respectively; p = 0.004). On the other hand, after PBSCT the absolute numbers of total circulating lymphocytes and lymphocyte subpopulations were not significantly different from those after BMT. The incidence of acute GvHD after PBSCT was the same as that after BMT, while chronic GvHD developed more frequently after PBSCT than after BMT (p = 0.005). In a pediatric population, the indications for PBSCT and BMT should be based on these findings in addition to regard for the donor's safety. [source] Allograft with unrelated donor accentuates the gastrointestinal toxicity associated with high-dose melphalan and total body irradiation preparative for bone marrow transplantation in childrenPEDIATRIC TRANSPLANTATION, Issue 4 2000K. Vettenranta Abstract: The use of high-dose melphalan ( l -phenyalalanine mustard or l -PAM) has been shown to be associated with both hematological and non-hematological toxicity. It has been employed in the conditioning for allogeneic stem cell transplants from related donors but experience on its use in the unrelated setting has not been reported. As an attempt to elucidate the role of high-dose l -PAM (210 mg/m2) and total body irradiation (TBI) as a preparative regimen for allogeneic marrow transplantation from matched unrelated donors, they were employed in an institutional pilot series of seven pediatric patients. When compared with recipients of unrelated marrow grafts conditioned using other regimens, those treated with high-dose l -PAM experienced a markedly more severe acute graft-vs.-host disease (GvHD). The overall incidence of grade III,IV acute GvHD was higher (86% vs. 14%) among those treated with l -PAM. As judged by gastrointestinal (GI) symptoms, clinically significant (stages ++ to ++++) gut GvHD was strikingly more prevalent among those treated with l -PAM (86% vs. 9%, p<0.005). Toxic mortality prior to day +100 was 29% in the l -PAM group and 9% in the non- l -PAM group of patients. With a mean follow-up of 21 months no increase in the incidence of chronic GvHD has been encountered among those conditioned with l -PAM. We conclude that the use of preparative L -PAM for allogeneic transplants from unrelated donors is associated with considerable procedure-related toxicity. We strongly suggest its use in this setting to be viewed with caution. [source] | ||||||||||||||||||||||||||||||||||