Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reconstitution of lethally irradiated mice with a mixture of syngeneic and allogeneic (A+B-->A) bone marrow results in multilineage mixed allogeneic chimerism, donor-specific transplantation tolerance, superior immunocompetence and resistance to graft-vs-host disease. However, the morbidity and mortality associated with lethal irradiation would be a major limitation to the clinical application of chimerism to induce tolerance for solid organ grafts or treat other nonmalignant hematologic diseases. We report here that durable multilineage mixed allogeneic chimerism and donor-specific transplantation tolerance for skin and primarily vascularized allografts can be achieved across multiple histocompatibility barriers using a nonmyeloablative radiation-based approach. The percentage of B10 mouse recipients that engrafted directly correlated with the degree of disparity between donor and recipient and the dose of total body irradiation administered. Although the occurrence of engraftment following conditioning with doses of total body irradiation of > or = 600 cGy was similar for animals receiving bone marrow disparate at MHC or MHC, minor and hematopoietic (Hh-1) loci (67% vs 78%), the level of donor chimerism was significantly less when multiple histocompatibility barriers were present (94.6 +/- 3.8% vs 37.5 +/- 12.5%). Treatment of the recipient with cyclophosphamide 2 days following allogeneic bone marrow transplantation reduced the dose of radiation sufficient for reliable engraftment to only 500 cGy of total body irradiation, regardless of MHC and Hh-1 disparity. Donor chimerism was stable and present in all lineages, with production of lymphoid (T and B cell), NK, and myeloid (erythrocyte, platelet, granulocyte, and macrophage) cells. Mixed chimeras exhibited donor-specific tolerance in vitro, as assessed by mixed lymphocyte culture (MLR) and cytotoxicity (CML) assays, and in vivo to skin and primarily vascularized cardiac allografts. The observation that engraftment and tolerance can be achieved across multiple histocompatibility barriers using nonmyeloablative recipient conditioning may allow allogeneic bone marrow transplantation to be applied to nonmalignant disease states in which lethal conditioning cannot be justified, including the induction of donor-specific tolerance for solid organ transplantation and the treatment of hemoglobinopathies and enzyme deficiency states.
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PMID:A nonlethal conditioning approach to achieve durable multilineage mixed chimerism and tolerance across major, minor, and hematopoietic histocompatibility barriers. 759 73

Granulocyte colony-stimulating factor (G-CSF) has been reported to exacerbate vaso-occlusive crises in sickle cell disease. It has been recommended to avoid its use for stem cell mobilization in this population, yet autologous transplant is the standard of care and at times a life-saving treatment for patients with various hematologic malignancies such as relapsed aggressive lymphoma or multiple myeloma. We report 5 cases of patients with sickle cell disease and related hemoglobinopathies who underwent granulocyte-colony stimulating factor (G-CSF)-mobilization of peripheral blood stem cells (PBSC). Three of them developed manageable vaso-occlusive pain symptoms requiring parenteral narcotics alone. The 2 others had no complications. These cases demonstrate that stem cell mobilization using G-CSF, although complicated and not without risk, is feasible in patients with sickle cell syndromes.
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PMID:Granulocyte colony-stimulating factor-based stem cell mobilization in patients with sickle cell disease. 1848 98

Hematopathologists encounter bone marrow biopsy specimens with marrow necrosis relatively infrequently; when necrosis is seen, determining the clinical significance can be challenging. While bone marrow necrosis is not uncommon in site-directed biopsy specimens or autopsy material, substantial necrosis is much less common in nondirected bone marrow biopsy specimens. Retrospective review showed the prevalence of bone marrow necrosis to vary between 0.3% and 2% antemortem, depending on the patient population. Numerous causes of bone marrow necrosis have been identified, including malignancy, radiation/chemotherapy, medication, infection, autoimmune disease, disseminated intravascular coagulation, antiphospholipid syndrome and other thrombotic disorders, granulocyte-colony stimulating factor (G-CSF) exposure, and hemoglobinopathies. Clinical findings associated with bone marrow necrosis include bone pain and fever, cytopenias, elevated LDH and ferritin, and leukoerythroblastosis. Rarely, such as in fat embolization syndrome (FES), bone marrow necrosis can be associated with thrombotic microangiopathy, neurologic dysfunction, and multiorgan failure. A thorough review of the patient's clinical record (including medical history, clinical presentation, and other laboratory findings), a thorough morphologic review of the bone marrow with appropriate ancillary stains, and an appreciation of the causes of bone marrow necrosis in different patient populations are required to determine the underlying cause of bone marrow necrosis. The purpose of this review is to present a strategy for evaluation of bone marrow necrosis found in an antemortem biopsy specimen.
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PMID:How I investigate bone marrow necrosis. 3142 33