1/22. Transfusion-associated graft-versus-host disease: an in situ hybridization analysis of the infiltrating donor-derived cells in the cutaneous lesion.BACKGROUND: Acute graft-versus-host disease (GVHD) can occur after a blood transfusion. OBJECTIVE: In order to elucidate the pathomechanisms responsible for transfusion-associated GVHD, infiltrating donor-derived cells in a cutaneous lesion were analyzed. methods: A skin sample obtained from a 69-year-old woman who developed fatal GVHD after blood transfusions from male donors was studied by performing in situ hybridization (ISH) with a Y-chromosome-specific probe. RESULTS: The cell infiltrates comprised mainly CD3 T lymphocytes. immunohistochemistry and ISH in combination demonstrated that 99% (182/184) of the Y-body-positive cells were CD3 . Y bodies were observed in 80% of the CD8 cells in the epidermis and dermoepidermal junction and in 77 and 45% of the CD8 and CD4 cells, respectively, in the dermis. CONCLUSION: These findings suggest that both CD4 and CD8 cells of donor origin were involved in the development of cutaneous GVHD.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/22. Hematopoietic donor chimerism and graft-versus-myeloma effect in relapse of multiple myeloma after allogeneic bone marrow transplantation.A large group of patients relapsing after allogeneic bone marrow transplantation (BMT) have obtained remission after infusion of leukocytes from their original donor, suggesting a graft-versus-myeloma effect. However, side effects such as graft-versus-host disease and myelosuppression are severe, and sometimes fatal, complications of this therapeutic approach. Previously we demonstrated that patients with leukemia who lack donor hematopoiesis in relapse after BMT experience severe and lasting aplasia after infusion of donor leukocytes. In two patients - one with extramedullary and one with marrow relapse after a sex-mismatched transplantation - we analyzed hematopoietic chimerism by cell sorting and bone marrow cultures. CD34-positive cells, CD4-CD8-positive cells, committed progenitors, and LTC-IC were of donor origin, as demonstrated by two-color fluorescence in situ hybridization (FISH). Additionally, in relapse complete donor T-cell chimerism was seen. In contrast, plasma cells were of recipient origin in the patient who had a relapse in the bone marrow. Both patients were treated with infusions of donor leukocytes from their original donor. Neither patient suffered myelosuppression, and one achieved a stable complete remission.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
3/22. Topical treatment of cutaneous chronic graft versus host disease with halofuginone: a novel inhibitor of collagen type i synthesis.BACKGROUND: In chronic graft-versus-host disease (cGvHD), skin fibrosis, contractures, and an increase in collagen content form the hallmark. We report a successful treatment of a cGvHD patient by topical application of halofuginone, an inhibitor of collagen alpha1(I) gene expression. methods: Halofuginone-containing ointment was applied daily on the left side of the neck and shoulder of a cGvHD patient. Collagen alpha1(I) gene expression and collagen content in skin biopsy specimens were evaluated by in situ hybridization and sirius red staining, respectively. RESULTS: After 3 and 6 months, a marked reduction in skin collagen synthesis was observed, accompanied with increase neck rotation on the treated side. After cessation of treatment, the sclerosis, skin tightness, and collagen alpha1(I) gene expression returned to baseline level. No adverse effects were observed, and no plasma levels of halofuginone could be detected. CONCLUSIONS: Halofuginone may provide a promising novel and safe therapy for cGvHD patients.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
4/22. Acute heart failure after allogeneic blood stem cell transplantation due to massive myocardial infiltration by cytotoxic T cells of donor origin.A 17-year-old male with AML FAB M4 relapsed 4 months after myeloablative conditioning and peripheral blood stem cell transplantation (PBSCT) from an HLA-identical unrelated donor. A second PBSC harvest was infused 2 days after completion of cytoreductive therapy with mitoxantrone 7 mg/m(2)/day i.v. for 3 days (total dose 21 mg/m(2)), fludarabine 30 mg/m(2)/day i.v. for 6 days (total dose 180 mg/m(2)) and Ara-C 125 mg/m(2)/day i.v. for 5 days (total dose 625 mg/m(2)). Neutrophil recovery occurred on day 10 and was associated with GVHD grade III of the skin which was treated with cyclosporin A (CsA) and prednisone. Because of fever of unknown origin and progressive fatigue combined with hypotension on day 15 after second PBSCT, echocardiography was performed which revealed a dramatic decrease in systolic function compared to the status pre-transplant. On the same day acute heart failure with consecutive ventricular fibrillation occurred. Although resuscitation was performed immediately the patient died. The autopsy revealed massive infiltration by donor CD8-positive lymphocytes with concomitant extensive damage of the heart tissue. Acute myocarditis of viral origin was excluded by in situ hybridization and nested PCR techniques. In this patient, myocardial involvement by acute GVHD seems to have triggered a fatal arrhythmia and heart failure.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
5/22. Ocular manifestation of acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation.A 26-year-old woman with acute myeloid leukemia underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical brother. Eighteen days after transplantation, the patient developed grade II acute graft-versus-host disease (GVHD) and was treated with corticosteroids. On day 38, the patient complained of eye pain and lacrimation. A slitlamp examination revealed corneal ulcers and pseudomembranous formation in both eyes. Histologic and immunohistochemical examinations of the pseudomembrane disclosed an infiltrate dominated by T cells. A cytogenetic study of the pseudomembrane by fluorescence in situ hybridization identified a y chromosome in the infiltrated mononuclear cells. Surveillance cultures from conjunctival swabs were negative. Thus, we diagnosed these ocular manifestations as an ocular involvement of acute GVHD.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
6/22. Acute graft-versus-host disease of the lung after liver transplantation.We describe the first case of a man who developed acute graft-versus-host disease (GVHD), isolated to the lung, after an orthotopic liver transplant from a female donor. Our patient experienced dyspnea, worsening hypoxemia, and a progressive obstructive ventilatory defect 12 days after liver transplantation. Open-lung biopsy revealed grade 2 lymphocytic bronchiolitis, the pathologic and immunologic correlate of acute pulmonary GVHD. Fluorescent in situ hybridization confirmed donor cells at sites of peribronchiolar inflammation. High-dose corticosteroids were given with a return to baseline pulmonary function. The current case should alert clinicians to investigate pulmonary GVHD as a potential cause of postoperative dyspnea in liver transplant recipients.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
7/22. diagnosis of transfusion-associated graft-versus-host disease by genetic fingerprinting and polymerase chain reaction.A patient with Hodgkin's disease (clinical stage IIIB) received chemotherapy and total nodal irradiation. After the transfusion of filtered packed red cells, this patient developed transfusion-associated graft-versus-host disease (TA-GVHD). The genetic fingerprint of the patient's peripheral blood lymphocytes (PBLs) differed completely from that of her other body tissues. Normally, after transfusion, only the patient's own genetic fingerprints are observed in the PBLs, as exemplified in more than 10 control cases in which the transfused blood had not been filtered before transfusion. No signal bands corresponding to those of the blood donor could be demonstrated in samples of the patient's tissue dna. Moreover, chimerism was detected in the hybridization pattern of the patient's PBLs on the ninth day after the onset of symptoms. Polymorphic simple repeats in the HLA-DRB gene after amplification by polymerase chain reaction were also investigated, which confirmed the fingerprinting results. The advantages of these methods for the diagnosis of TA-GVHD include the rapid and unequivocal diagnosis as well as the fact that there is no need for the relatives to be HLA typed.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
8/22. Sustained cytogenetic remission induced by imatinib mesylate in a chronic myeloid leukemia patient who had a relapse into lymphoid crisis after allogeneic hematopoietic stem cell transplantation.We report on the response to imatinib mesylate in a chronic myeloid leukemia patient who, after undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) for treatment of lymphoid blastic crisis, had a relapse into blastic crisis despite the presence of chronic and grade II acute graft-versus-host disease (GVHD). Complete hematologic response and the disappearance of the Bcr-Abl fusion signal on fluorescence in situ hybridization analysis were achieved after 10 weeks of imatinib therapy and were maintained for 26 months with no adverse effects, including recurrence of GVHD. This case highlights the ability of imatinib to induce sustained hematologic and cytogenetic remission in some patients who have had relapses into advanced-stage chronic myeloid leukemia after alloHSCT.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
9/22. Successful unmanipulated haploidentical bone marrow transplantation from an HLA 2-locus-mismatched mother for wiskott-aldrich syndrome after unrelated cord blood stem cell transplantation.The authors describe a boy with wiskott-aldrich syndrome (WAS) who was diagnosed immediately after birth using flow cytometric and genetic analysis. At 1 year of age he received unrelated cord blood stem cell transplantation (UCBSCT); however, the sex chromosomes of the peripheral blood mononuclear cells showed that the recipient type was over 70%. This rate gradually increased to over 90% after immunosuppressant therapy was discontinued. Clinical manifestations, including high fever, graft-versus-host disease (GVHD)-like eruptions, and signs of infection recurred. Results of flow cytometric and genetic analysis of mononuclear cells from the boy's mother were normal with no mutation. Three months after UCBSCT, he received an unmanipulated HLA-haploidentical 2-locus-mismatched bone marrow transplant (BMT) from his mother. The prophylaxis against GVHD was tacrolimus and short-term methotrexate. Hematopoietic reconstitution was rapid and fluorescence in situ hybridization analysis revealed sustained engraftment. Grade II acute GVHD developed but improved rapidly with the administration of methylprednisolone. The patient is progressing well and displays complete chimerism 2 years after the BMT. This case suggests that unmanipulated haploidentical BMT from the mother might be feasible not only for malignant disease but also for immunodeficiency disease patients who urgently need stem cell transplants and have no HLA-identical donors.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
10/22. Transfusion-associated graft-versus-graft and potential graft-versus-host disease in a renal allotransplanted patient.Transfusion-associated graft-versus-host disease (GVHD) is a rare but often fatal condition. We report on a case in which a 54-year-old man with polycystic kidneys shortly after receiving a male cadaver donor kidney developed severe intractable rejection and symptoms of GVHD. in situ hybridization with a y chromosome- "specific" dna probe and combined in situ hybridization and immunohistochemistry with monoclonal antibodies defining cellular phenotypes were performed on biopsy and tissue specimens taken at rejection episodes and from the lost allograft. The vast majority of infiltrating leukocytes in the morphologically rejecting kidney parenchyma were of female origin and consisted mainly of T lymphocytes and macrophages. This could only be explained by engraftment of leukocytes received in connection with transfusion of female whole blood in association with the transplantation. The patient developed symptoms of GVHD, and graftectomy was performed due to life-threatening cytomegalovirus infection. This case of combined "graft"-versus-graft disease and GVHD indicates that precautions in the administration of blood transfusion to severely immunosuppressed patients should be taken. We recommend the use of gamma-irradiated and lymphocyte-depleted blood products.- - - - - - - - - - ranking = 0.4keywords = hybridization (Clic here for more details about this article) |
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