Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 44-year-old patient who had had acute monoblastic leukemia developed an osteosarcoma of the pelvic bones 5 years after an allogeneic bone marrow transplant from his HLA-identical sister. He had additionally received superficial cutaneous radiation of the legs and pelvis, over the 3 weeks prior to total body irradiation (TBI), because of cutaneous leukemic lesions. The tumor was a fibrohistiocytomatous osteogenic sarcoma. The first lesion was in the right ilium, and a second lesion appeared 18 months later, symmetrically on the left ilium. Despite treatment, the patient died from metastases. At the time of diagnosis of radiation-induced sarcoma, the patient was free of leukemia and had several risk factors already reported to favor the development of solid tumors in stem cell recipients. These include acute leukemia, TBI and graft-versus-host disease. As he developed symmetrical lesions of the pelvic bone, and because of the histology of the radiation-induced tumor, we assumed that the additional radiation of the skin prior to TBI may have contributed to the pathogenesis of this malignant fibrous histiocytoma. Therefore, the risk/benefit ratio should be carefully considered in unusual indications. These patients should benefit from a close follow-up of the superimposed areas.
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PMID:Radiation-induced bone sarcoma following total body irradiation: role of additional radiation on localized areas. 1080 73

Thalidomide, initially introduced as a sedative, was withdrawn from the market in the early 1960s after it was found to be a teratogen. However, it later found use as an investigational agent in the treatment of erythema nodosum leprosum, oral ulcers, graft versus host disease, and wasting associated with the human immunodeficiency syndrome. Its antiangiogenic properties were recognized in the early 1990s during a period where the importance of angiogenesis became increasingly apparent as a critical step in the in the proliferation and spread of malignant neoplasms. This led to the evaluation of thalidomide as an antiangiogenic agent in the treatment of several cancers. Thalidomide has already become part of standard therapy for the treatment of patients with relapsed and refractory multiple myeloma. It has also been found to have varying degree of benefit in various other malignancies. Although more clinical trials are needed, Kaposi' s sarcoma and myelofibrosis represent other malignancies in which thalidomide has already demonstrated promising activity. The mechanism of action of thalidomide in cancer is still unclear, but do appear to be mediated by several other mechanisms in addition to its anti-angiogenic properties. This article reviews the current status of thalidomide for the treatment of non-plasma-cell malignancies.
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PMID:Thalidomid: current role in the treatment of non-plasma cell malignancies. 1519 11

Our objective was to study the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond Syndrome (SDS). Among 71 SDS patients included in the French Severe Chronic Neutropenia Registry, 10 received HSCT between 1987 and 2004 in five institutions. The indications were bone marrow failure in five cases, and myelodysplastic syndrome (MDS) or leukemia in five cases. The median follow-up of patients who survived without relapse is 6.9 years (3.1-16.8 years). The conditioning regimen consisted of a busulfan-cyclophosphamide combination (n=6) or total body irradiation plus chemotherapy (n=4). Six patients received stem cells from unrelated donors and four from identical siblings. Engraftment was complete in eight patients and unassessable in two patients. These latter two patients died of infections 32 and 36 days after HSCT, with grade IV graft-versus-host disease and multiorgan dysfunction. A third patient died from an acute respiratory distress syndrome 17 months after HSCT with progressive granulocytic sarcoma. One patient had an MDS relapse 4 months after HSCT and died 10 months later. The overall 5-year event-free survival rate is 60+/-15%. We conclude that HSCT is feasible for patients with SDS who develop bone marrow failure or malignant transformation.
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PMID:Hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: experience of the French neutropenia registry. 1615 25

Recently, a number of medications approved for nondermatologic use have proved useful against dermatologic diseases. This article reviews the dermatologic uses and effects of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops. Deferasirox--an oral iron chelator--could be an effective treatment against porphyria cutanea tarda, hemochromatosis, and pathogens such as mucor that thrive in iron rich environments. Bortezomib, a proteasome inhibitor and multiple myeloma treatment, may be effective against nodular amyloid and has been effectively used against squamous cell carcinoma; although trials demonstrate it is ineffective against metastatic melanoma. Bortezomib has many cutaneous side effects including erythematous plaques or nodules, a generalized morbilliform erythema with ulcerations and fever, purpuric eruptions, leukocytoclastic vasculitis, Sweet's syndrome, and folliculitis. Dasatinib is a multi-targeted tyrosine kinase inhibitor active in vitro against most cell lines containing BCR-ABL mutations that confer resistance to imatinib. Dasatinib is likely to be effective against dermatofibroma sarcoma protuberans and cutaneous acute lymphoblastic leukemia, and has caused panniculitis. Cyclosporine 0.05% ocular emulsion (eye drops) are approved to treat dry eyes including dry eyes caused by collagen vascular disease. Cyclosporine eye drops might also have utility in treating eye pathology of ocular rosacea, atopic keratoconjunctivitis, graft versus host disease, herpes keratitis, chronic sarcoidosis of the conjunctiva, conjunctival manifestations of actinic prurigo, keratitis of keratitis-ichthyosis deafness (KID) syndrome, and lichen planus-related kerato-conjunctivitis. This article speculates that cyclosporine eye drops would also be useful for any disease causing ectropion or eclabion of the eye as well as toxic epidermal necrolysis-related eye pathology (in particular corneal scarring).
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PMID:A review of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops: possible uses and known side effects in cutaneous medicine. 1737 1

Isolated extramedullary relapse after allogeneic bone marrow transplantation (BMT) for acute myeloblastic leukemia (AML) is very unusual, particularly in patients with graft versus host disease (GVHD) known to be associated with decreased incidence of leukemic relapses. However, these rare occasions have been suggested to result from the escape of leukemic cells at the immune-privileged sites. Here we report two unusual post-transplant cases with AML: the first developed testicular relapse during the treatment of chronic GVHD (cGVHD) and bronchiolitis obliterans and the second relapsed as granulocytic sarcoma in the proximal tibia two years after BMT.
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PMID:Isolated testicular and bone relapse in children with acute myeloblastic leukemia and chronic graft versus host disease after allogeneic BMT. 1790 24

Isolated primary granulocytic sarcoma is a rare disease that presents as an extramedullary tumor of myeloid lineage cells. Most patients subsequently develop acute myelogenous leukemia (AML) within a short period, and their prognosis is poor. Herein, we report the case of a 33-year-old woman with a primary isolated granulocytic sarcoma which originated in the small intestine. After she recovered from surgery, she received intensive chemotherapy equivalent to that for AML, followed by allogeneic bone marrow transplantation from an HLA-matched, unrelated donor. Four years after the transplantation, she remains in complete remission without graft-versus-host disease or any other symptoms. This case illustrates the effectiveness of our therapeutic strategy for isolated granulocytic sarcoma, not only with surgical resection of the tumor and intensive chemotherapy equivalent to that for AML, but also with allogeneic bone marrow transplantation, performed while no sign of AML is observed.
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PMID:Isolated granulocytic sarcoma of the small intestine successfully treated with chemotherapy and bone marrow transplantation. 1836 39

Second primary cancers are approximately 2.1-2.8 times more common in survivors of bone marrow transplant than in the age-matched general population. We describe a patient who developed high-grade sarcoma in two disparate sites that were clinically involved by chronic cutaneous graft versus host disease (GVHD). This occurred 3.5 years after bone marrow transplant for acute myelogenous leukemia (AML). This suggests that malignant sarcomas may develop in the setting of chronic GVHD, and close surveillance of GVHD-related nodules is warranted.
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PMID:Soft tissue sarcoma in the setting of chronic cutaneous graft versus host disease after allogenic bone marrow transplantation. 1858 56

Chronic generalized immune activation represents one of the most critical features determining progression to AIDS. This may result in the manifestation of malignancy, with lymphoma and Karposi's sarcoma being the first to be recognised. In this regard, the manifestation of lymphoma is very similar to that seen in transplant patients and those with graft versus host disease (GVHD) where both chronic immune activation and immune suppression are present. Unlike the latter conditions which involve HLA mismatch, the source of this phenomenon during HIV infection remains elusive. Despite a lifecycle adapted to the host and possessing a plethora of survival strategies, HIV promotes disease progression in a manner that is consistently associated with the HLA repertoire suggesting pathogenic features relating to immunological incompatibility may be at the root of disease. Here we review the influence of immune activation on progression to AIDS with particular reference to molecular mimicry and autoimmune phenomenon and highlight the therapeutic potential of non-neutralizing antibodies and strategies designed to diffuse immune activation.
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PMID:HIV induced AIDS and related cancers: chronic immune activation and future therapeutic strategies. 1905 48

Mesenchymal stem cells (MSCs) are the most popular among the adult stem cells in tissue engineering and regenerative medicine. Since their discovery and functional characterization in the late 1960s and early 1970s, MSCs or MSC-like cells have been obtained from various mesodermal and non-mesodermal tissues, although majority of the therapeutic applications involved bone marrow-derived MSCs. Based on its mesenchymal origin, it was predicted earlier that MSCs only can differentiate into mesengenic lineages like bone, cartilage, fat or muscle. However, varied isolation and cell culturing methods identified subsets of MSCs in the bone marrow which not only differentiated into mesenchymal lineages, but also into ectodermal and endodermal derivatives. Although, true pluripotent status is yet to be established, MSCs have been successfully used in bone and cartilage regeneration in osteoporotic fracture and arthritis, respectively, and in the repair of cardiac tissue following myocardial infarction. Immunosuppressive properties of MSCs extend utility of MSCs to reduce complications of graft versus host disease and rheumatoid arthritis. Homing of MSCs to sites of tissue injury, including tumor, is well established. In addition to their ability in tissue regeneration, MSCs can be genetically engineered ex vivo for delivery of therapeutic molecule(s) to the sites of injury or tumorigenesis as cell therapy vehicles. MSCs tend to lose surface receptors for trafficking and have been reported to develop sarcoma in long-term culture. In this article, we reviewed the current status of MSCs with special emphasis to therapeutic application in bone-related diseases.
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PMID:Therapeutic potential of adult bone marrow-derived mesenchymal stem cells in diseases of the skeleton. 2050 59

An 18-year-old male underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myeloid leukemia (CML) in the first late chronic phase. On day 132, he was readmitted to the hospital with nausea, vomiting and nodular lesions on endoscopy. A diagnosis of granulocytic sarcoma of the stomach was made. Bone marrow cytogenetic analysis for the Philadelphia chromosome and nested polymerase chain reaction for BCR-ABL1 were both negative. Immunosuppression was abruptly discontinued, and by day 180, all gastric lesions had completely disappeared. However, there were histological signs of graft-versus-host disease. The patient developed progressive anorexia and elevated hepatic enzymes, which prompted the reintroduction of cyclosporine. Considering the risk of another relapse, imatinib mesylate (IM) 600 mg/day was started. The patient Is condition improved, and there was no evidence of disease recurrence at 36 months after relapse. Relapse of CML is the commonest cause of treatment failure after allo-HSCT. On rare occasions, a localized extramedullary presentation is seen. Unless properly treated, other extramedullary relapse sites and/or marrow infiltration usually occur. Withdrawal of immunosuppression, along with IM therapy seems to be an acceptable approach in this setting.
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PMID:Granulocytic sarcoma of the stomach: relapse after hematopoietic stem-cell transplantation for chronic myeloid leukemia. 2054 44


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