Cases reported "Graft vs Host Disease"

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1/574. Verruciform xanthoma associated with squamous cell carcinoma.

    Verruciform xanthoma (VX) is a rare lesion of unknown etiology that is typically solitary and predominantly located within the oral cavity. Less commonly, they arise on the skin, with the majority of cases occurring in anogenital sites. They can be confused clinically with verruca vulgaris, condyloma, leukoplakia, verrucous carcinoma, and squamous cell carcinoma. Histologic features include acanthosis with uniform elongation of the rete ridges and xanthomatous cells that lie in and are typically confined to the papillary dermis. Although epidermal atypia is not a characteristic finding, we describe an unusual case of VX that has features of both VX and squamous cell carcinoma. In addition, there was a VX with typical histologic characteristics located at a separate site in the same patient. This case is also the first to our knowledge to be reported on the neck and axilla and is the third case associated with cutaneous graft versus host disease secondary to bone marrow transplant for acute lymphoblastic leukemia.
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2/574. Late graft rejection and second infusion of bone marrow in children with aplastic anaemia.

    Late graft rejection following allogeneic bone marrow transplantation (BMT) for aplastic anaemia is a significant clinical problem and is associated with a high risk of mortality. We report two children with severe aplastic anaemia (SAA) who developed very late graft rejection 2 years and 4 months and 10 years respectively after allogeneic BMT from HLA-identical siblings. Following a second BMT from their initial donors, engraftment has been sustained in both cases. The patients are alive with full donor chimaerism, 18 and 19 years from initial transplant. These cases illustrate that graft failure can be an extremely late event after allogeneic BMT for SAA, and that long-term sustained engraftment can be achieved in these patients with second BMT from the original donors.
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3/574. scedosporium apiospermum sinusitis after bone marrow transplantation: report of a case.

    A forty-year-old man underwent an allogeneic BMT from his HLA identical sister. GvHD prophylaxis was done with cyclosporine (CyA), methotrexate and prednisone (PDN). On day 90 extensive GvHD was noted and higher doses of immunosuppressive drugs alternating CyA with PDN were initiated. Patient's follow-up was complicated by intermittent episodes of leukopenia and monthly episodes of sinusitis or pneumonia. One year after BMT, the patient developed hoarseness and nasal voice. No etiologic agent could be identified on a biopsy sample of the vocal chord. Upon tapering the doses of immunosuppressive drugs, the patient had worsening of chronic GvHD and was reintroduced on high doses of cyclosporine alternating with prednisone on day 550. Three months later, GvHD remained out of control and the patient was started on azathioprine. On day 700, hoarseness and nasal voice recurred. Another biopsy of the left vocal chord failed to demonstrate infection. Episodes of sinusitis became more frequent and azathioprine was withheld 3 months after it was started. One month later, the patient had bloody nasal discharge and surgical drainage of maxillary sinuses was performed. Histopathology showed hyphae and cultures grew scedosporium apiospermum. itraconazole 800 mg/day was initiated. The patient developed progressive respiratory failure and died 15 days later.
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4/574. Chronic eosinophilic leukemia: successful treatment with an unrelated bone marrow transplantation.

    The optimal treatment of eosinophilic leukemia is still uncertain. We report the successful treatment of a 21-year-old patient with eosinophilic leukemia, without cytogenetic abnormalities, by bone marrow transplantation from an unrelated donor. The conditioning regimen for the transplantation consisted of fractionated total body irradiation and cyclophosphamide. Acute GVHD, grade I, post-transplantation was successfully treated. No other severe complications occured. The patient is alive in complete remission 21 months after unrelated bone marrow transplantation.
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5/574. Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation.

    dyskeratosis congenita is recognized by its dermal lesions and constitutional aplastic anemia in some cases. We report successful allogeneic bone marrow transplantation in two siblings with this disease from their sister, and their long term follow-up. We used reduced doses of cyclophosphamide and busulfan for conditioning instead of total body irradiation. Also, we report late adverse effects of transplantation which are not distinguishable from the natural course of disease.
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6/574. Induction of hyperacute graft-vs-host disease after donor leukocyte infusions.

    BACKGROUND: Infusions of leukocytes obtained from the original bone marrow donor is a new approach for treating patients who have a relapse of leukemia after allogeneic bone marrow transplantation. Up to 90% of patients who achieved remission developed graft-vs-host disease (GVHD). However, any description of the clinical and histologic features in these cases is lacking. OBSERVATIONS: We describe 2 patients in whom a severe, peculiar, hyperacute, fatal GVHD developed after treatment with donor leukocyte infusions and interferon alfa. The patients had not received any additional chemotherapy or GVHD prophylaxis. In both patients, the eruption started with the appearance of erythematous plaques at the interferon alfa injection sites, and a generalized maculopapular eruption subsequently developed. The clinical lesions evolved from acute to lichenoid within several days. The histologic examination also demonstrated unusual findings and showed features of both acute and chronic lichenoid GVHD. CONCLUSIONS: Donor leukocyte infusions without GVHD prophylaxis may provoke a severe fatal hyperacute GVHD. In the cases presented herein, we discuss the significance of the rapid clinical evolution from acute to lichenoid and the combination of histologic features of both acute and chronic GVHD in the biopsy specimens.
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7/574. Extramedullary tumors of myeloid blasts in adults as a pattern of relapse following allogeneic bone marrow transplantation.

    BACKGROUND: Extramedullary tumors of lymphoid and myeloid blasts outside the well-defined sanctuaries following allogeneic bone marrow transplantation (allo-BMT) are rare. Little is known about the biology, treatment, and outcome of these tumors in this setting. methods: In this retrospective analysis, 134 consecutive patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) who underwent allo-BMT at a single institution between 1990 and 1998 were reviewed. Five cases of isolated extramedullary myeloid sarcoma that occurred as patterns of recurrence following allo-BMT between 1990 and 1998 are reported. These patients were treated with radiotherapy, systemic chemotherapy, or a second allo-BMT. Clinical outcome is compared with posttransplantation bone marrow relapses observed during the same period at the same institution. The literature on the clinical characteristics, currently available treatment, and outcome of posttransplantation myeloid sarcoma patients was reviewed. RESULTS: Excluding isolated skin and central nervous system recurrences, the frequency of extramedullary myeloid sarcoma encountered as a relapse pattern following allo-BMT was determined to be 3.7% among patients with acute or chronic leukemia of myeloid origin. The survival of patients who were managed with radiotherapy and systemic chemotherapy was less than 4 months. A patient who underwent a second allo-BMT following local radiotherapy is alive and in complete remission more than 33 months after the diagnosis of myeloid sarcoma. The median survival of 17 patients with posttransplantation bone marrow relapse following allo-BMT was 2.2 months. When posttransplantation medullary recurrences are analyzed, patients with CML had a median survival of 12 months, with a significantly better 5-year survival rate than patients with AML (0 vs. 60%, P = 0.015; median survival, 12 months). CONCLUSIONS: The clinical outcomes of patients with recurrent isolated extramedullary myeloid sarcoma following allo-BMT are poor, as in any leukemic relapse, with the exception of patients with CML in this setting.
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8/574. Disseminated nocardiosis in a bone marrow transplant recipient with chronic GVHD.

    We describe a case of disseminated nocardiosis in a 53-year-old male allogeneic marrow recipient with chronic GVHD, 15 years post BMT. Six months prior to admission he was treated for recurrent chronic GVHD with corticosteroids with a good response. He deteriorated subsequently while still on steroids requiring admission for fever, anorexia, weight loss, productive cough and progressive dyspnoea. On admission he had multiple nodular lesions on chest roentgenogram and subsequently grew nocardia farcinica in blood culture. N. farcinica is rare post BMT, has a high mortality, is resistant to various antibiotics and needs prolonged antimicrobial therapy. We report the successful management of our patient with single agent trimethoprim-sulphamethoxazole.
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9/574. thalidomide in children undergoing bone marrow transplantation: series at a single institution and review of the literature.

    thalidomide has one of the most notorious drug histories because of its teratogenicity. Its widespread use in the 1960s led to a worldwide epidemic of phocomelia in inborns; this in turn led to its complete ban in most of the world. However, it has now been licensed for selected indications including graft-versus-host-disease (GVHD) after bone marrow transplantation, wasting associated with tuberculosis and human immunodeficiency virus infection, and leprosy. Little is known, however, about its use in children in these settings. Therefore, we report our experience and review the literature on thalidomide in children for GVHD after bone marrow transplantation. We studied 6 patients, 2 with chronic GVHD, 2 with acute GVHD, and 2 with acute GVHD progressing into chronic disease. One patient with chronic GVHD had a complete response, whereas the other had a partial response. Side effects consisted primarily of sedation and constipation, which are reported previously and well known side effects. None had neuropathy. One patient had rash, eosinophilia, and early pancreatitis that began shortly after initiation of thalidomide, persisted, and resolved only after discontinuation of thalidomide. eosinophilia and pancreatitis are both previously unreported side effects or associated findings of thalidomide treatment. review of the literature reveals three major studies of thalidomide in GVHD; of these two included children and adults together, and one in which age range of patients was not mentioned. In addition, four series of children receiving only thalidomide are reported. These series contained 1 to 14 patients each. Results show efficacy in at least 50% of children with chronic GVHD and little or no efficacy in children with exclusively acute GVHD. Side effects are similar to those reported in adults and consisted mostly of sedation and constipation, both of which subsided over time and resolved after discontinuing the drug. We speculate on the reasons for which thalidomide is more effective in chronic, compared with acute, GVHD in children, and make recommendations for future study.
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10/574. Treatment of graft versus host disease (GVHD) by photopheresis?

    Graft versus host disease (GVHD), whether acute or chronic, is a frightening complication of bone marrow allografts-indeed in many cases it can be life threatening. In chronic GVHD, the symptoms are less serious, but they can nevertheless be alarming. The mechanism of this reaction is very complex and the pathogenesis of chronic GVHD seems to be slightly different from that of acute GVHD. However, there is no doubt about the immune mechanisms. The production of numerous cytokines plays an important part and has also been des-cribed. Until the use of photopheresis, the only treatments that were effective to any degree have been immunosuppressive treatments. Extracorporeal photopheresis (ECP), a technique recently proposed in chronic GVHD, is promising and is believed to attack the actual cause of the disease (the role of cytotoxic T lymphocytes is now recognized). ECP is believed to have a complex mechanism of action, the explanation of an anti-T lymphocyte action of ECP seems too simple. We report the results of three patients suffering from chronic GVHD, refractory to the usual treatments. The schedule for ECP was a cycle of two treatments every 2 weeks. We recorded a complete remission for patient No. 1 (grade 1) with no relapse for now 3 years. In patient No. 2 (grade 2-3) a progressive improvement was observed in the various symptoms with, however, several episodes of aggravation. In patient No. 3 (grade 2-3), the skin symptoms improved and the lichen planus lesions healed after only 15 months of treatment (interrupted by two infectious episodes during which ECP was stopped). Although the study population was small, we may be justified in thinking that ECP can cause an improvement in chronic GVHD refractory to immunosuppressive treatment. These results should be confirmed by a rigorously designed multicentre study.
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