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

Between 1985 and 1989, eight children underwent two successive bone marrow transplantations. The initial disease was chronic myelomonocytic leukemia in three patients, chronic myelocytic leukemia in two, acute M7 nonlymphoblastic leukemia in one, sickle cell anemia in one, and thalassemia major in one. The preparation in view of the second grafting included high-dose chemotherapy in all patients, associated with antithymocytic globulin transfusion and total nodal irradiation in three patients. Hematological recovery was similar after both graftings. Infectious complications were not more common following the second graft than after the first one. On the other hand, the rates of rejection and graft-versus-host disease were lower, probably due to a more intensive immunosuppressive therapy. The prognosis of chronic leukemia relapsing after a first graft does not seem to be improved by a second attempt.
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PMID:Second bone marrow transplantation in eight children. 146 68

Five children with sickle cell anaemia underwent bone marrow transplantation (BMT) for severe clinical disease. The conditioning regimen for BMT was in busulfan plus cyclophosphamide. The allograft contained more than 5 x 10(8) nucleated cells per kg recipient. Prophylaxis of GVHD consisted of methotrexate and cyclosporin A. Therapy was well tolerated. Duration of neutropenia (less than 0.5 x 10(9)/l) was short (14-25 d). Platelet recovery (greater than 50 x 10(9)/l) occurred between day 12 and 45. The patients have been followed up for 8-28 months. No major infections occurred and long-term BMT-related toxicity was limited to mild, chronic GVHD in one patient. Mean haemoglobin levels remained above 10 g/dl. Haemoglobin electrophoresis showed AS patterns in all grafted patients--all marrow donors having sickle cell trait. From our preliminary data, we conclude that BMT or sickle cell anaemia is curative, well tolerated and should be proposed for suitable patients.
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PMID:Bone marrow transplantation for severe sickle cell anaemia. 153 96

Bone marrow transplantation represents the technical application of basic immunologic principles to the treatment of a variety of neoplastic and allied disorders that originate in the bone marrow. The results have improved during the past 15 years, being most striking for the treatment of the acute and chronic leukemias. The promise of autologous bone marrow transplantation for the treatment of leukemias and solid tumors is awaiting the perfection of techniques for the effective removal of residual neoplastic cells as well as more effective therapy. The use of this technique at its present stage of development for the treatment of benign hematologic disorders, which cause severe morbidity (ie, thalassemia or sickle cell anemia), is controversial, raises serious ethical issues, and cannot be recommended routinely at this time. Complications of bone marrow transplantation such as graft rejection, graft-versus-host disease, and opportunistic infections are discussed.
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PMID:Bone marrow transplantation: a review. 266 96

The fetus is the preferred candidate for transplantation for a number of reasons. First, the fetal period is the earliest time at which an identified disorder can potentially be treated. If a fetus is identified with a treatable disorder in utero, and if that disorder can affect fetal development, then treatment during fetal life is potentially beneficial. A second advantage of in utero fetal HSC transplantation is the immunotolerance of the fetus, making it both a favorable donor and a favorable recipient. Finding a histocompatible donor and minimizing GVH disease are major concerns in bone marrow HSC transplantation. Fetal immuno-tolerance may eliminate the need for the former and significantly reduce the incidence and severity of the latter. The first hematologic disorders for fetal HSC transplantation may be sickle cell disease and the thalassemias, as recent technologic developments allow diagnosis in the first trimester. However, the potential targets for in utero fetal HSC transplantation are numerous and include a variety of genetic disorders of lymphocyte, platelet, leukocyte, red cell, and enzyme function. Disadvantages of in utero fetal HSC transplantation exist. First, it is necessary to have identified the fetus as being at risk for a genetic disorder, before the prenatal diagnosis can be made. This happens in one of two ways--either a previous pregnancy resulted in an affected fetus, or the parents of the fetus have been identified as being carriers of the genetic disorder.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In utero fetal hematopoietic stem cell transplantation. 286 75

Marrow transplantation is effective treatment for a number of haematological diseases in patients under the age of 50 who have an HLA-identical sibling donor. It is generally successful when used early in the treatment of aplastic anaemia. It is the only treatment that offers long-term disease-free survival for patients with acute leukaemia who have relapsed at least once, with 10-30 per cent apparent cures. Although still somewhat controversial, it appears also to be the treatment of choice for patients with acute non-lymphoblastic leukaemia in first chemotherapy induced remission and for those with chronic myelogenous leukaemia in the chronic phase since approximately 50-60 per cent of these patients are surviving after marrow transplantation in complete remission, apparently cured. Marrow grafting is the only effective treatment for many patients with inherited immunological-deficiency diseases and certain genetic storage diseases. It is being explored for the therapy of patients with lymphoma, Hodgkin's disease, multiple myeloma, small-cell lung cancer, testicular cancer, ovarian cancer and genetic disorders of haematopoiesis. Cures of congenital Fanconi anaemia, Blackfan-Diamond anaemia, osteopetrosis, and paroxysmal nocturnal haemoglobinuria have been achieved by marrow grafting. Genetic disorders associated with haemolytic anaemia and cyclic neutropenia have been cured by marrow grafting in animals. Target disorders for marrow transplantation in humans are thalassaemia major and sickle cell disease, and, indeed, a first successful transplant for treatment of thalassaemia major has recently been described (Thomas et al, 1982). Marrow transplantation has been limited by the fact that many patients do not have HLA-identical siblings and very few have monozygotic twins. The Seattle team has now explored the use of less well-matched family member donors in more than 80 patients with leukaemia. These donors share one HLA haplotype genetically with the patient and are phenotypically identical at two of the three major HLA loci on the other HLA haplotype (Clift et al, 1979). Overall, the post-transplant survival appears more a reflection of the type and stage of the leukaemia than of the marrow donor. Patients with leukaemia grafted in relapse have a projected survival of 20-30 per cent and those transplanted in remission of 50 per cent. The incidence and severity of GVHD may not be significantly different from that of patients given HLA-identical sibling marrow grafts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Application of bone marrow transplantation in leukaemia and aplastic anaemia. 635 79

Fifteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 3/y) vaso-occlusive crises (VOC) associated with recurrent acute chest syndrome episodes (n = 10), osteitis (n = 3), osteonecrosis (n = 3), strokes (n = 3) or frequent massive deglobulisation (n = 2). Two children undergone splenectomy, two were chelated and two had an erythroid allo-immunization. Ethnic origins were from various countries in Africa (n = 11), North-Africa (n = 3) or West Indies (n = 1). At BMT, they were 2y 3m to 14y 9m old (mean: 8y 7m). Donors were AS (n = 11) or AA (n = 4). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n = 13) or 260 mg/kg (n = 2); BU: 14 mg/kg (n = 1), 16 mg/kg (n = 9), > 16 mg/kg (n = 5); one patient received also TLI and the last two anti-thymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n = 4) or CSA plus short-term MTX (n = 11). Median follow-up is 28 months (5 m to 53 m). All patients had an engraftment (d12 to d32) with a stable total chimerism in 10/14 patients. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (35 m follow-up) without any manifestation of SCD, with a high stable 22% Hb F level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of severe forms of sickle cell anemia with bone marrow allograft: French experience (15 cases). SFGM]. 833 53

Bone marrow transplantation (BMT) is the only treatment currently available which can cure thalassaemia and sickle cell anaemia. However, it is not without risk and the complications of graft failure, GVHD, veno-occlusive disease, interstitial pneumonitis and infections, together with the toxicity of the conditioning therapy result in a transplant-related mortality in children of 10-20%. For the survivors, long-term sequelae include chronic GVHD, endocrinopathies and an increased incidence of secondary malignancies. The decision to offer BMT to a patient with a haemoglobinopathy must be based on a knowledge of the relative risks of transplant and conventional therapy. However, in sickle cell anaemia, a subset of patients with particularly severe disease can be identified at an early age when the risks associated with BMT are at their lowest. In thalassaemia, chelation therapy can delay the onset of organ damage due to hypertransfusion but is unlikely to prevent it entirely. The results of BMT in children without organ impairment are excellent and BMT must now be considered a real alternative to conventional treatment. Gene therapy is an exciting prospect for the future but recent progress in retroviral gene transfer has been hindered by poor infection efficiencies and expression levels in the target cells. The identification of the positive regulatory elements of both the alpha- and beta-globin genes may resolve some of these problems. Finally, alternative gene delivery systems are being investigated, but the introduction of gene therapy for the haemoglobinopathies into clinical practice may need to await successful gene targeting and replacement.
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PMID:Bone marrow transplant for the haemoglobinopathies: past, present and future. 835 16

Twenty eight patients underwent bone marrow transplantation (BMT) for sickle cell anemia in Belgium. The patients were originating from Central Africa, were young and symptomatic. Engraftment occurred in all patients and was sustained in 25. In 3 patients, a bone marrow rejection was observed. One of these patients underwent a second BMT and had an uneventful recovery. One patient died 3 months after BMT of graft-versus-host disease (GVHD). Twenty seven patients are alive and 25 are free of vaso-occlusive related manifestations with a follow-up ranging from 4 to 78 months. So far, eight patients went back to Africa and continue to do well.
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PMID:Bone marrow transplantation in sickle cell disease: the Belgian experience. 837 50

Fourteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 4/y) vasoocclusive crises (VOC) and recurrent acute chest syndrome episodes (n:10), osteitis (n:3), osteonecrosis (n:3), strokes (n:3) or frequent massive deglobulisation (n:2). Two children undergone splenectomy, 2 were chelated and 2 had erythroid allo-immunization. Ethnic origins were from various countries in Africa (n:10), North-Africa (n:3) or West Indies (n:1). At BMT, they were 2y 3m to 14y 9m old (mean:8y 7m). Donors were AS (n:11) or AA (n:3). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n:12) or 260 mg/kg (n:2); BU:14 mg/kg (n:1), 16 mg/kg (n:9), > 16 mg/kg (n:4); 1 patient received also TLI and one other antithymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n:4) or CSA plus short-term MTX (n:10). Median follow-up was 23 months (8 m. to 48 m.). All patients had an engraftment (d13 to d32) with a stable total chimerism in 10/14 patients who are cured. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (28 m. follow-up) without any manifestation of SCD, with a high stable 22% Hb F level. One patient developed an aplastic anaemia 15 m after BMT: a second BMT was achieved 21 m after the first one with engraftment and total chimerism. Two patients have a relatively stable partial chimerism with still undergoing CSA therapy (11 m. and 23 m. follow-up).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation (BMT) in 14 children with severe sickle cell disease (SCD): the French experience. GEGMO. 837 51

Two children affected by severe aplastic anaemia and sickle cell anaemia rejected the allogeneic bone marrow transplantation from an HLA-matched unrelated volunteer and an HLA-identical sibling, respectively. In both cases a second transplant using granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) was performed. Donors were the HLA-haploidentical mother and the same HLA-identical sibling who was employed for the first marrow allograft, respectively. Treatment with G-CSF and PBSC collection were well tolerated. Both patients had engraftment of donor haemopoiesis and did not experience severe graft-versus-host disease. These cases confirm that PBSC transplant should be considered as a feasible treatment to reverse graft failure in paediatric patients.
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PMID:Recombinant human G-CSF-mobilized peripheral blood stem cells for second allogeneic transplant after bone marrow graft rejection in children. 860 13


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