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Acute Graft-versus-host Disease (acute + graft-versus-host_disease)
Selected AbstractsFatal Graft-Versus-Host Disease Presenting as Fever of Unknown Origin in a Pancreas-After-Kidney Transplant RecipientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2008F. L. Weng Acute graft-versus-host disease (GVHD) is a rare complication of pancreas transplantation. We describe a 54-year-old male with type 1 diabetes who received a zero-antigen mismatched pancreas-after-kidney transplant from a pancreas donor who was homozygous at the HLA-B, -Cw, -DR, and -DQ alleles. Starting on postoperative day (POD) #22, the patient developed persistent fevers. Workup was notable only for low-grade cytomegalovirus viremia, which was treated. The fevers eventually disappeared. On POD #106, the patient was noted to have a diffuse erythematous rash. A skin biopsy was consistent with GVHD. Short tandem repeat DNA analysis of both peripheral blood lymphocytes and skin demonstrated mixed chimerism, confirming the diagnosis of GHVD. Soon after diagnosis, the patient developed pancytopenia and fevers and died of multiorgan failure on POD #145. Transplant clinicians should consider GVHD as a possible, although admittedly rare, cause of fevers of unknown origin in recipients of pancreas transplants. [source] The corticosteroid-induced inhibitory effect on NK cell function reflects down-regulation and/or dysfunction of triggering receptors involved in natural cytotoxicityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2004Chiara Vitale Abstract Corticosteroids are known to inhibit NK cell functions. However no information is available on whether such inhibition may affect the expression and/or the function of receptors involved in NK cell activation. In an attempt to analyze this point, we studied peripheral blood NK cells isolated from pediatric patients undergoing allogeneic BM transplantation. NK cells were analyzed before, during and after methylprednisolone administration to treat acute graft-versus-host disease. In NK cells freshly isolated from peripheral blood during methylprednisolone treatment, the surface expression of activating receptors, particularly NKp46 and NKp30, was consistently reduced. Such impaired expression could also be detected after 5,days of culture in IL-2. Such cultured NK cells also failed to express the IL-2-inducible NKp44 receptor. Accordingly, cytotoxicity against different tumor target cell lines was sharply reduced. The effect on NK cells isolated from healthy individuals and cultured in the presence of methylprednisolone was also analyzed. A similar inhibitory effect occurred in the expression of activating NK receptors. In addition, a sharp impairment of NK cytotoxicity against different tumor target cell lines or immature DC was detected. [source] Association of IL-6 gene polymorphism with the outcome of allogeneic haematopoietic stem cell transplantation in Czech patientsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4-5 2008Z. Ambruzova Summary Interleukin-6 (IL-6) is an important pro-inflammatory mediator implicated in immune-mediated complications of allogeneic haematopoietic stem cell transplantation (aHSCT). In accord with previous reports, this preliminary study on 56 donor,recipient pairs revealed IL-6-174 single nucleotide polymorphisms as a risk factor for the development of acute graft-versus-host disease and decreased survival after aHSCT. [source] Immunomodulation by mesenchymal stem cells and clinical experienceJOURNAL OF INTERNAL MEDICINE, Issue 5 2007K. Le Blanc Abstract Mesenchymal stem cells (MSCs) from adult marrow can differentiate in vitro and in vivo into various cell types, such as bone, fat and cartilage. MSCs preferentially home to damaged tissue and may have therapeutic potential. In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T-cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T-cells. In vivo, MSCs prolong skin allograft survival and have several immunomodulatory effects, which are presented and discussed in the present study. Possible clinical applications include therapy-resistant severe acute graft-versus-host disease, tissue repair, treatment of rejection of organ allografts and autoimmune disorders. [source] Pustular acral erythema in a patient with acute graft-versus-host diseaseJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2003DP Ruiz-Genao ABSTRACT Acral erythema is a well-known side-effect of chemotherapy treatment but it is not common in patients undergoing bone marrow transplant. We report a post-transplant patient with clinical and histological acute graft-versus-host disease (GVHD) who concurrently developed acral erythema presenting as painful, well-defined and self-limiting palmar erythema with pustules. A skin biopsy from the palm showed abnormal keratinocyte maturation and eccrine squamous syringometaplasia. This case illustrates the difficulties in establishing the differential diagnosis of cutaneous eruptions in patients undergoing bone marrow transplant. [source] Acquired Ichthyosis as a Manifestation of Acute Cutaneous Graft-Versus-Host DiseasePEDIATRIC DERMATOLOGY, Issue 1 2007Jennifer Huang M.D. While some authors have suggested the association of acquired ichythosis with cutaneous graft-versus-host disease, the evidence to support this association is rare. We describe a patient who developed enteritis secondary to acute graft-versus-host disease and had concomitant ichthyosiform lesions. Several months later, he was diagnosed with cutaneous graft-versus-host disease. This patient is presented to suggest that acquired ichthyosis is an underrecognized manifestation of acute cutaneous graft-versus-host disease. Given the important prognostic implications of this diagnosis, we recommend a low threshold for performing a skin biopsy to rule out GVHD in the appropriate clinical setting. [source] Polyclonal anti-T-cell globulin as part of the preparative regimen for pediatric allogeneic stem-cell transplantationPEDIATRIC TRANSPLANTATION, Issue 4 2001Mats Remberger Abstract: To prevent graft rejection and graft-versus-host disease (GvHD) after allogeneic stem-cell transplantation (ASCT), 56 children were given polyclonal anti-T-cell globulin (ATG) as part of the conditioning regimen. Of the 56 children in the cohort, 27 had a non-malignant disease and 29 had different hematological malignancies. Eight were in first remission of leukemia and the remainder in later stages. Donors were in 16 cases a human leucocyte antigen (HLA)-identical sibling and in 40 a matched unrelated donor (MUD). The control group comprised 16 patients with an HLA-identical donor; the children in this group were not treated with ATG. Side-effects related to the ATG treatment occured in 63% of the patients and included fever, chills, headache, dyspnoea, nausea/vomiting, body pain, fall in blood pressure, and transient respiratory arrest. Engraftment occured in 55 (98%) of the ATG-treated patients at a median of 17 (11,27) days after ASCT. One rejection occured at 23 days post-SCT. The probabilities of acute graft-versus-host disease (GvHD) of grades II,IV were 6% for patients with an HLA-identical donor, 12% for controls, and 26% for the MUD group. Chronic GvHD occured in 20%, 50%, and 50% of patients in the three groups, respectively. Transplant-related mortality rates at 100 days were 6%, 6%, and 7%, respectively. The 5-yr survival rate was 94% and 81% using sibling donors, with and without ATG respectively, and 53% using unrelated donors (p =,0.002). Disregarding donor type, among the ATG-treated patients 5-yr survival rates were 46% in patients with a malignant disease and 77% in non-malignant disorders. Relapse and relapse-free survival rates were 42% and 46%, respectively. Five out of 12 patients who showed an early full donor chimerism in the T-cell lineage developed acute GvHD of grades II,IV, compared to none out of 13 patients being mixed chimeras (p =,0.01). Hence, the use of polyclonal ATG as part of conditioning prior to ASCT in children is safe and the survival rate encouraging. [source] Impact of alemtuzumab as conditioning regimen component on transplantation outcomes in case of CMV-seropositive recipients and donorsAMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2008Yee Soo Chae We studied the incidence of cytomegalovirus (CMV) infection, clinical outcomes, and complications in 39 recipients of alemtuzumab-containing conditioning-stem cell transplantation, who were classified into two groups based on the median dose (35 mg) of alemtuzumab. All the recipients and donors were CMV-seropositive before transplantation. The median survival duration was 321 days (range, 46,1098 days) and the 2-year survival rate was 47.8%. The probability of nonrelapse mortality at 100 days and 2 years was 14.6% and 31.2%, respectively. The cumulative incidence of Grade II-IV acute graft-versus-host disease (GVHD) at Day 100 was 21.8%. The overall incidence of chronic GVHD (cGVHD) was 28.6%, including a 17.9% incidence of extensive cGVHD. The cumulative incidence of CMV antigenemia was 68.0%. There were no statistical differences in the engraftment, acute and cGVHD, relapse, CMV antigenemia, and overall survival (OS) between the two groups. Yet, the nonrelapse mortality (NRM) was significantly lower for the low-dose group (5.9% vs. 51.7%, P = 0.010). The present study showed that alemtuzumab was effective for GVHD prevention, yet caused a relatively high incidence of CMV antigenemia, regardless of the dose. Thus, a low dose of alemtuzumab (, 35 mg) would seem to be preferable in an allogeneic SCT setting when both the recipient and the donor are CMV seropositive. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] Determining a Maximum-Tolerated Schedule of a Cytotoxic AgentBIOMETRICS, Issue 2 2005Thomas M. Braun Summary Most phase I clinical trials are designed to determine a maximum-tolerated dose (MTD) for one initial administration or treatment course of a cytotoxic experimental agent. Toxicity usually is defined as the indicator of whether one or more particular adverse events occur within a short time period from the start of therapy. However, physicians often administer an agent to the patient repeatedly and monitor long-term toxicity due to cumulative effects. We propose a new method for such settings. It is based on the time to toxicity rather than a binary outcome, and the goal is to determine a maximum-tolerated schedule (MTS) rather than a conventional MTD. The model and method account for a patient's entire sequence of administrations, with the overall hazard of toxicity modeled as the sum of a sequence of hazards, each associated with one administration. Data monitoring and decision making are done continuously throughout the trial. We illustrate the method with an allogeneic bone marrow transplantation (BMT) trial to determine how long a recombinant human growth factor can be administered as prophylaxis for acute graft-versus-host disease (aGVHD), and we present a simulation study in the context of this trial. [source] The human leucocyte antigen-G 14-basepair polymorphism correlates with graft-versus-host disease in unrelated bone marrow transplantation for thalassaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2007Giorgio La Nasa Summary The presence of the 14-bp insertion polymorphism of the human leucocyte antigen (HLA)-G gene (HLA-G) promotes immune tolerance through increased synthesis of HLA-G molecules. We investigated this polymorphism in a large cohort of 53 thalassaemia patients transplanted from an unrelated donor. Sixteen patients (30·2%) homozygous for the 14-bp deletion had a higher risk of developing acute graft-versus-host disease (aGvHD) than patients homozygous for the 14-bp insertion (,14-bp/,14-bp vs +14-bp/+14-bp: Relative Risk = 15·0; 95% confidence interval 1·59,141·24; P = 0·008). Therefore, the 14-bp polymorphism could be an important predictive factor for aGvHD following bone marrow transplantation. [source] T- and B-cell immune reconstitution and clinical outcome in patients with multiple myeloma receiving T-cell-depleted, reduced-intensity allogeneic stem cell transplantation with an alemtuzumab-containing conditioning regimen followed by escalated donor lymphocyte infusionsBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2003Shirley D'Sa Summary. Immune reconstitution after conventional allogeneic transplantation is a major determinant of survival. We conducted a detailed investigation of T- and B-cell immune reconstitution and clinical outcome in 19 patients with multiple myeloma undergoing reduced-intensity stem cell transplantation using in vivo T-cell depletion with alemtuzumab. These patients experienced delayed T-cell recovery, particularly in the naïve (CD45 RA+) CD4 compartment. T-cell receptor spectratype analysis showed a reduced repertoire diversity, which improved rapidly after the administration of donor leucocyte infusions and subsequent conversion to full donor T-cell chimaerism. Post-transplant recovery of CD19+ B cells was also delayed for up to 18 months. Spectratype analysis of IgH CDR3 repertoire revealed a gradual normalization in IgM spectratype complexity by 6,12 months after transplant. There was a high incidence of viral infection, particularly cytomegalovirus reactivation, but the regimen-related mortality was low, perhaps because of the very low incidence of acute graft-versus-host disease (GVHD; grade I-II skin GVHD was seen in 5/19 patients). Over 80% of all patients have relapsed at a median of 283 (range 153,895) d after transplant, suggesting that the initially low rate of GVHD comes at a high price with regard to the desired graft-versus-myeloma effect. [source] Varicella-zoster virus infection in adult patients after unrelated cord blood transplantation: a single institute experience in JapanBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2003Akira Tomonari Summary. Varicella-zoster virus (VZV) infection was studied in 40 adult patients who underwent cord blood transplantation (CBT) from unrelated donors. Twenty-five patients developed VZV reactivation at a median of 5 months after CBT (range 1·7,26 months). The cumulative incidence of VZV reactivation after CBT was 80% at 30 months. Twenty-two patients developed localized herpes zoster. The remaining three patients developed atypical non-localized herpes zoster, which was associated with visceral dissemination in one patient. All the patients responded well to antiviral therapy. Unexpectedly, the absence of grade II,IV acute graft-versus-host disease (GVHD) was associated with a higher rate of VZV reactivation after CBT (100% versus 55%, P = 0·01). These results suggest that recovery of VZV-specific immune responses after CBT is delayed even in patients without severe acute GVHD. [source] Changes of isoagglutinin titres after ABO-incompatible allogeneic stem cell transplantationBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003Je-Hwan Lee Summary. We investigated the changes in isoagglutinin titres in 62 patients who underwent ABO-incompatible allogeneic stem cell transplantation. After major [and/or (±) minor] ABO-incompatible transplantation, recipient-derived isoagglutinins against donor-type red blood cells (RBCs) disappeared more rapidly in unrelated recipients (P = 0·006) and in patients with acute graft-versus-host disease (GVHD, P = 0·025) than in sibling recipients and in patients without acute GVHD respectively. Pure red cell aplasia (PRCA) developed in 10 out of 35 evaluable patients who underwent major (± minor) ABO-incompatible transplantation, and the post-transplant increase of isoagglutinin titres was a significant predictor for the occurrence of PRCA. In five out of 36 patients who underwent minor (and/or (±) major) ABO-incompatible transplantation, donor-derived isoagglutinins against recipient RBCs were detectable without clinically overt haemolysis. Isoagglutinin titres against ABO antigens absent both on recipient and donor RBCs decreased during the early post-transplant period then rose subsequently in 24 out of 29 patients at (median) d 59 post transplant. Our study showed that changes in isoagglutinin titres might have clinical implications in the occurrence of immunohaematological complications such as PRCA or immune-mediated haemolysis, and might reflect immunohaematological reconstitution after transplantation. Furthermore, our data regarding time to disappearance of recipient-derived isoagglutinins against donor-type RBCs after major ABO-incompatible transplantation suggest the presence of a graft-versus-plasma cell effect. [source] Disparity for the minor histocompatibility antigen HA-1 is associated with an increased risk of acute graft-versus-host disease (GvHD) but it does not affect chronic GvHD incidence, disease-free survival or overall survival after allogeneic human leucocyte antigen-identical sibling donor transplantationBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2001David Gallardo Disparity for the minor histocompatibility antigen HA-1 between patient and donor has been associated with an increased risk of acute graft-versus-host disease (GvHD) after allogeneic human leucocyte antigen (HLA)-identical sibling donor stem cell transplantation (SCT). However, no data concerning the impact of such disparity on chronic GvHD, relapse or overall survival are available. A retrospective multicentre study was performed on 215 HLA-A2-positive patients who received an HLA-identical sibling SCT, in order to determine the differences in acute and chronic GvHD incidence on the basis of the presence or absence of the HA-1 antigen mismatch. Disease-free survival and overall survival were also analysed. We detected 34 patient,donor pairs mismatched for HA-1 antigen (15·8%). Grades II,IV acute GvHD occurred in 51·6% of the HA-1-mismatched pairs compared with 37·1% of the non-mismatched. The multivariate logistic regression model showed statistical significance (P: 0·035, OR: 2·96, 95% CI: 1·07,8·14). No differences were observed between the two groups for grades III,IV acute GvHD, chronic GvHD, disease-free survival or overall survival. These results confirmed the association between HA-1 mismatch and risk of mild acute GvHD, but HA-1 mismatch was not associated with an increased incidence of chronic GvHD and did not affect relapse or overall survival. [source] Hemorrhagic cystitis: a retrospective single-center surveyCLINICAL TRANSPLANTATION, Issue 5 2007Zuzana Hassan Abstract:, Severe hemorrhagic cystitis (HC) may be a life-threatening complication in allogeneic stem cell transplantation (SCT). In order to improve the strategies for prophylaxis and treatment, we retrospectively analyzed data on patients who underwent SCT at our center from 1990 through 2005. Patients with HC were identified through our database and their medical charts were reviewed. Grades 2,5 and 3,5 HC developed in 109/834 patients (13.1%) and 27/834 patients (3.2%), respectively. The frequency of HC decreased over the time from 18.0% in 1990,1992 to 9.5% in 2002,2005 (p = 0.005). HC started on a median of 35 (0,166) days post-transplant and persisted for a median of 23 (2,270) days. Transplant-related mortality was 21% in patients without HC, 15% in those with HC of grade 2, 55% in those with grade 3, and 71% in patients with HC of grades 4,5 (p < 0.001). In multivariate analysis, the risk factors for HC were myeloablative conditioning, busulphan, cytomegalovirus infection, hematological malignancy, and acute graft-versus-host disease (aGVHD). With four risk factors, the risk of HC development was 31%. Risk factors for severe HC of grades 3,5 were aGVHD and bacteremia. [source] Treatment of severe acute graft-versus-host disease with anti-thymocyte globulinCLINICAL TRANSPLANTATION, Issue 3 2001Mats Remberger Severe acute graft-versus-host disease (GVHD) is one of the major complications after haematopoietic stem-cell transplantation (HSCT). Treatment of severe GVHD is difficult and the condition is often fatal. One proposed method of improving the therapy is to include anti-thymocyte globulin (ATG). Here, we will report our results in 29 patients using ATG as part of treatment for severe steroid-resistant acute GVHD. Four patients suffered from grade II, 13 from grade III and 12 from grade IV GVHD. Median time to grade II GVHD was 24 d (range 7,91 d) and to grade III was 29 d (range 8,55 d) after HSCT. Five different ATG preparations were used, rabbit ATG (R-ATG), BMA 031, OKT® -3, ATG-Fresenius and Thymoglobuline®. All patients had skin involvement, 26 also had gut involvement and 25 had liver involvement. The rate of response to treatment was best in skin involvement (72%), while liver and gut involvement showed lower response rates (38%). Eleven patients survived more than 90 d, 7 of them developed chronic GVHD, 1 developed mild GVHD, 1 developed moderate GVHD and 5 developed severe GVHD. Survival at 100 d was 37% and at 1 yr it was 12%. Most patients died of GVHD, with virus or fungal infections as contributing causes of death. To conclude, treatment of severe acute GVHD is difficult and ATG, in our hands, adds nothing to conventional pharmacological treatment. [source] | ||||||||||||||||||||||||||||