1/99. Epstein-Barr virus (EBV) associated B-cell lymphoproliferative disease following HLA identical sibling marrow transplantation for aplastic anaemia in a patient with an EBV seronegative donor.BACKGROUND: B-cell lymphoproliferative disorders (BLPD*) caused by Epstein-Barr virus (EBV) occurring after allogeneic bone marrow transplantation (BMT) are usually of donor origin. Treatment such as discontinuation of immunosuppression may be successful in some cases, but infusion of donor T cells results in successful eradication of EBV BLPD in most cases. methods AND RESULTS: We report a case of EBV positive aggressive BLPD after HLA matched sibling BMT for aplastic anaemia. The tumour completely regressed after withdrawal of cyclosporin and donor lymphocyte infusion. However, although the tumor was of donor origin, the donor serum was negative for antibodies to EBV antigens and no EBV-specific cytotoxicity was detected in donor peripheral blood mononuclear cells. The recipient was seropositive for EBV before BMT. CONCLUSIONS: We speculate that a 'second primary' EBV infection occurred involving donor cells in the recipient during BMT immunosuppression, with subsequent outgrowth of donor-derived BLPD. EBV infection may have been by an endogenous EBV isolate, from external sources, or from third party transfusions.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
2/99. Bone marrow aplasia with prominent atypical plasmacytic proliferation preceding acute lymphoblastic leukemia.A two-year-old boy presented with pancytopenia. bone marrow examination revealed an aplastic marrow with prominent immature plasma cell proliferation, which mimicked plasma cell leukemia. immunohistochemistry, however, revealed a polyclonal population consistent with a reactive process, excluding plasma cell neoplasia. Administration of granulocyte-colony stimulating factor resulted in recovery of normal hematopoiesis with resolution of plasmacytosis. Seven months later, the patient had an elevated white blood cell count and bone marrow findings diagnostic of acute lymphoblastic leukemia. To the best of our knowledge this is the first reported case of bone marrow aplasia with prominent polyclonal plasmacytosis presenting as a prodrome of acute lymphoblastic leukemia in childhood.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
3/99. T cell lymphoproliferative disorder following bone marrow transplantation for severe aplastic anemia.Post-transplant lymphoproliferative disorder (PTLD) is uncommonly of T cell origin, especially following BMT. We describe a 13-year-old boy with severe aplastic anemia (SAA) and no evidence of Fanconi's anemia who underwent BMT at 11 years of age using CY 10 mg/kg once daily i.v. on days -5, -4, antilymphocyte globulin (ALG) 30 mg/kg once daily i.v. on days -5 approximately -3 and CsA from day -1 as conditioning. The BMT failed and he received a further peripheral blood stem cell transplant (PBSCT) 240 days after BMT. Conditioning was with CY 50 mg/kg once daily i.v. on days -5 approximately -2, and ALG 15 mg/kg once daily i.v. on days -4 approximately -2. GVHD prophylaxis included CsA and MTX. Engraftment was later confirmed by cytogenetic studies. Desquamation and ulcers of the oral mucosa and mouth angle developed in the 13th month post PBSCT. A buccal mucosa biopsy on day 524 revealed only plasmacytosis. Immunosuppressants were discontinued at that point. Generalized lymphadenopathy, prolonged fever (waxing and waning) and facial swelling developed in the 18th month post PBSCT. A neck lymph node biopsy on day 601 showed T cell lymphoma of diffuse large cell type with monoclonal TCR gamma-chain gene rearrangement. A FISH study showed that the malignant T cells were of recipient origin. EBV in situ hybridization was negative. He did not receive further treatment apart from discontinuation of immunosuppressants. He was followed up in our out-patient clinic and showed good performance 1170 days post PBSCT. We speculate that a different mechanism was operating in the pathogenesis of T cell lymphoma in this case. risk factors include SAA and two transplants, conditioned with CY and ALG, long term use of CsA and treatment with azathioprine.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
4/99. Quantitative monitoring of circulating Epstein-Barr virus dna for predicting the development of posttransplantation lymphoproliferative disease.Epstein-Barr virus (EBV)-dna was quantitatively measured to assess posttransplantation virus reactivation by real-time polymerase chain reaction (PCR). In the first retrospective analysis of a 7-year-old boy with lymphoproliferative disease (LPD) after an unrelated cord blood transplantation, serum EBV-dna progressively increased to 4 x 10(5) copies/mL. EBV load was then prospectively monitored in peripheral blood from posttransplantation patients. The second case was an 8 year-old boy with aplastic anemia who received a CD34 cell transplantation. This patient died of LPD with the progression of pulmonary nodules. EBV-dna increased to 4 x 10(4) copies/mL after the control of cytomegalovirus reactivation. On the other hand, EBV-dna was undetectable (<200 copies/mL) in the series of all 58 samples from 10 patients who did not develop LPD after hematopoietic stem cell transplantation. Sequential monitoring of circulating EBV-dna by quantitative PCR may be a useful indicator for predicting the development of posttransplantation LPD.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
5/99. Severe oral manifestations of chronic graft-vs.-host disease.BACKGROUND: Graft-vs.-host-disease, or GVHD, is the main cause of morbidity in patients who have received bone marrow transplants. Chronic GVHD, or cGVHD, occurs 100 days or more after the transplant procedure and may take the form of various oral manifestations. CASE DESCRIPTION: A 23-year-old woman received an allogeneic bone marrow transplant. Although prophylactic therapy was provided, the patient developed cGVHD. Appropriate therapy was initiated, and it received a good clinical response at all sites affected by cGVHD, except in the oral cavity. The patient received complete symptomatic relief through revised systemic therapy, improved oral hygiene, use of topical medications and a monitored diet. CLINICAL IMPLICATIONS: Effective intervention by dentists is an important part of increasing treatment effectiveness and improving quality of life in patients who received bone marrow transplants.- - - - - - - - - - ranking = 0.2keywords = life (Clic here for more details about this article) |
6/99. risk factors for cytomegalovirus retinitis following bone marrow transplantation from unrelated donors in patients with severe aplastic anemia or myelodysplasia.Two cases of cytomegalovirus (CMV) retinitis following bone marrow transplantation (BMT) from unrelated donors are reported. 1 patient had been treated for severe aplastic anemia (SAA) and the other for hypoplastic myelodysplastic syndrome (MDS). Because first line therapy with antithymocyte globulin (ATG) and cyclosporin A (CsA) had failed, BMT was performed following a conditioning regimen of ATG, cyclophosphamide, and total lymphoid irradiation. Treatment for CMV retinitis was successfully carried out with gancyclovir (systemic and intraocular injection), foscarnet, and photocoagulation (Case 1) and gancyclovir and foscarnet (Case 2). Both patients also developed Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD). We compared these 2 cases with 14 SAA patients who did not develop CMV retinitis after BMT using marrow from either HLA-identical siblings (n = 9) or from unrelated donors (n = 5). Unlike the retinitis patients, the latter 5 patients received ATG only once. The retinitis patients had significantly lower CD4 T-cell levels in their peripheral blood than the 14 patients who did not develop CMV retinitis. We believe that repeated treatment with ATG and transplantation from unrelated donors may lead to immune dysfunction that could increase the likelihood of CMV retinitis, as well as LPD. For such BMT patients, regular ophthalmic examinations and careful testing for CMV antigenemia are recommended.- - - - - - - - - - ranking = 0.2keywords = life (Clic here for more details about this article) |
7/99. association of clonal T-cell large granular lymphocyte disease and paroxysmal nocturnal haemoglobinuria (PNH): further evidence for a pathogenetic link between T cells, aplastic anaemia and PNH.There is mounting evidence to suggest that T-cell-mediated suppression of haemopoiesis is a pathogenetic mechanism in three bone marrow failure syndromes: aplastic anaemia (AA), paroxysmal nocturnal haemoglobinuria (PNH) and myelodysplasia (MDS). T-cell microclones can be detected by sensitive polymerase chain reaction (PCR)-based methods in all three disorders. Recently, larger clonal populations of T-cell large granular lymphocytes (T-LGLs) have been observed in some patients with AA and MDS. Here, we report the development of a large clonal T-LGL population in a patient with bona fide PNH. In this patient, we defined part of the sequence of the T-cell receptor (TCR) beta-chain gene, and we have shown that the large T-LGL population emerged from a background of multiple smaller T-cell clones. Thus, T-LGL clones in AA, MDS and PNH probably expand as a result of antigenic stimulation. It is postulated that the antigen driving clonal T-cell proliferations in these disorders exists on haemopoietic stem cells.- - - - - - - - - - ranking = 0.2keywords = life (Clic here for more details about this article) |
8/99. A case of factitious aplastic anemia.OBJECTIVE: We report the case of factitiously induced aplastic anemia by the ingestion of busulfan, a bifunctional alkylating chemotherapeutic agent used in the treatment of chronic myelogenous leukemia. The medical consequences and financial costs of this illness are reported. The reader will gain an understanding of the relevant clues to the diagnosis of a factitious hematologic illness, the psychodynamic issues present in this case and the legal, ethical and countertransferential issues raised by the case. METHOD: A single case review including medical and billing records, patient and staff interviews and literature review. RESULTS: The covert ingestion of busulfan by this patient resulted in life-threatening bone marrow suppression, bilateral aseptic hip necrosis, transfusion-dependent thrombocytopenia and a chronic pain syndrome. Her treatment was complicated by noncompliance with prescribed treatments and polymicrobial sepsis possibly secondary to the self-injection of feces into her central line. To date, the total cost of care for the treatment of this patient's medical complications secondary to her ingestion of busulfan exceeds $1,100,000.00. CONCLUSIONS: This case underscores the importance of the early recognition by the primary care physician of the possibility of a factitious etiology of hematologic abnormalities such as aplastic anemia due to the ingestion of bone marrow ablative medications. The index of suspicion is increased when the patient is a young health care provider, usually female, with atypical pancytopenia and an unusual disease course and response to treatment.- - - - - - - - - - ranking = 0.2keywords = life (Clic here for more details about this article) |
9/99. Changes in T-cell receptor VB repertoire in aplastic anemia: effects of different immunosuppressive regimens.We studied the degree and the pattern of skewing of the variable region of beta-chain (VB) T-cell receptor (TCR) repertoire in aplastic anemia (AA) at initial presentation and after immunosuppression using a high-resolution analysis of the TCR VB complementarity-determining region 3 (CDR3). Age-matched healthy individuals and multitransfused patients with non-immune-mediated hematologic diseases were used as controls. In newly diagnosed AA, the average frequency of CDR3 size distribution deviation indicative of oligoclonal T-cell proliferation was increased (44% /- 33% vs 9% /- 9%; P =.0001); AA patients with human leukocyte antigen (HLA)-DR2 and those with expanded paroxysmal nocturnal hemoglobinuria clones showed more skewed VB repertoires. Nonrandom oligoclonal patterns were found for VB6, VB14-16, VB21, VB23, and VB24 subfamilies in more than 50%, and for VB15, VB21, and VB24 in more than 70% of AA patients with HLA-DR2. patients received immunosuppression with antithymocyte globulin (ATG)/cyclosporine (CsA) or cyclophosphamide (CTX) with CsA in combination, and their VB repertoire was reanalyzed after treatment. Whereas no significant change in the degree of VB skewing in patients who had received ATG was seen, patients treated with CTX showed a much higher extent of oligoclonality within all VB families, consistent with a profound and long-lasting contraction of the T-cell repertoire. VB analysis did not correlate with the lymphocyte count prior to lymphocytotoxic therapy; however, after therapy the degree of VB skewing was highly reflective of the decrease in lymphocyte numbers, suggesting iatrogenic gaps in the VB repertoire rather than the emergence of clonal dominance. Our data indicate that multiple specific clones mediate the immune process in AA.- - - - - - - - - - ranking = 0.2keywords = life (Clic here for more details about this article) |
10/99. Fatal post-transplant lymphoproliferative disorder following allogeneic bone marrow transplantation for aplastic anemia.Post-transplant lymphoproliferative disorder (PTLD) constitutes a serious complication of allogeneic bone marrow transplantation. We describe a case of PTLD in a twenty-six year-old male treated with bone marrow transplantation for aplastic anemia of unknown cause. The patient received unmanipulated marrow graft from his HLA-matched brother. Fifty-one days post transplant he developed progressive enlargement of cervical lymph nodes, followed by hepatosplenomegaly and generalized lymphadenopathy. Polymorphic PTLD was diagnosed basing on the lymph node histopathology, positive EBV detection, flow cytometry and IgH rearrangement studies proving monoclonality (capillary electrophoresis with ABI PRISM 310 Genetic Analyzer). There was no response to anti-CD20 antibody, cessation of immunosuppression, donor lymphocyte infusion and cytostatic therapy. The patient died on the 65th day of multiple organ failure. We discuss the diagnostics and management of PTLD in the setting of bone marrow transplantation.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
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