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)

A 37-year-old female highly alloimmunized by multiple transfusions received a sex matched HLA-identical unrelated bone marrow transplant for hypoplastic MDS-RA with moderate myelofibrosis. Conditioning consisted of total body irradiation, cyclophosphamide and ATG, GVHD prophylaxis consisted of CsA, MTX and prednisolone. The CD34+ stem cell content of the first graft was relatively low due to an inadequate harvest. The patient appeared not to have engrafted by day 23 post-BMT. She therefore received a second sex mismatched HLA-identical unrelated bone marrow graft on day 25 after two days of 3.5 mg/kg methylprednisolone from a different donor. Over the ensuing days, the first marrow showed slow engraftment followed by engraftment of the second graft. The first graft was then rejected, as monitored by peripheral blood studies of chimerism. No signs of acute GVHD were observed. Despite successful trilineage engraftment and complete second donor chimerism, the patient died from disseminated toxoplasmosis encephalitis and pneumonia on day +104.
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PMID:Second unrelated bone marrow transplantation without additional conditioning therapy after engraftment failure. 948 60

Allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) has in recent years become an alternative to allogeneic bone marrow transplantation because it facilitates rapid hematopoietic reconstitution without an increase in the incidence of severe graft-versus-host disease (GVHD). We report on a 61-year-old man with myelodysplastic syndrome (MDS) and myelofibrosis who received an allo-PBSCT from his HLA-matched 68-year-old brother. The preparative regimen consisted of busulfan and cyclophosphamide. Cyclosporin A and methotrexate were administered for GVHD prophylaxis. The donor was treated with granulocyte colony-stimulating factor (G-CSF) at a dose of 10 micrograms/kg/day subcutaneously for 4 consecutive days. A preparation of 4.04 x 10(6) CD34+ cells/kg recipient weight was collected in a single apheresis and infused immediately. Engraftment times to a neutrophil count greater than 500/microliter and platelet count greater than 2.0 x 10(4)/microliter were 15 days each. Acute GVHD of grade II developed, but was resolved with methylprednisolone. However, the patient died of thrombotic microangiopathy 97 days after his allo-PBSCT. Administration of G-CSF and apheresis in the donor were feasible and well tolerated. Allo-PBSCT may result in earlier engraftment and be especially beneficial to elderly patients with MDS.
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PMID:[Allogeneic peripheral blood stem cell transplantation in an elderly patient with myelodysplatic syndrome with myelofibrosis]. 1006 93

We report three acute myelogenous leukemia (AML) patients who developed intracerebral granulocytic sarcomas (GS) and were successfully treated with allogeneic BMT (allo-BMT). The diagnosis of one patient was AML M2 with myelofibrosis, and the other two patients were AML M4 with eosinophilia (AML M4 Eo), according to the FAB classification. Two patients first experienced a relapse in the brain that resulted in the formation of GS, followed by a relapse in the bone marrow. The remaining patient developed an optic nerve GS after suffering a bone marrow relapse. All three patients received irradiation for the GS and systemic chemotherapy before the allo-BMT. TBI was used for conditioning, and GVHD prophylaxis was with cyclosporine (CsA) and short-term MTX in all three cases. These patients are currently 9 to 37 months post-BMT without relapse. Thus, our experience suggests that allo-BMT is an effective treatment for AML patients with existing or pre-existing intracerebral GS.
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PMID:Three AML patients with existing or pre-existing intracerebral granulocytic sarcomas who were successfully treated with allogeneic bone marrow transplantations. 1067 89

Hematopoietic stem-cell transplantation (HSCT) is an effective mode of therapy in pediatrics for the treatment of both malignant and non-malignant disorders. We compared the course of children transplanted with unrelated umbilical cord blood (UCB) to those transplanted with allogeneic sibling bone marrow (BM) for bone marrow failure syndromes. Thirteen patients with a median age of 6.3 years were transplanted for the following diseases between April 1992 and November 1997: myelodysplastic syndromes, aplastic anemia, Diamond-Blackfan anemia, myelofibrosis, paroxysmal nocturnal hemoglobinuria, osteopetrosis and dyskeratosis congenita. The stem cell source was BM in ten patients and UCB in three. We retrospectively examined the conditioning regimens, stem cell source and dose, days to engraftment, survival and complication rate to see whether there was a significant advantage in using one source over the other. The median time to an absolute neutrophil count > 500 per microL was 25 days for UCB patients and 16 days for BM patients. The median time to a platelet count > 20,000 per microL was 55 days for UCB patients and 22 days for BM patients. The 100-day mortality was 66% in UCB patients and 20% in BM patients. The overall mortality rates were 66% and 40%, respectively. Three patients died prior to engraftment. Seven patients (54%) were still alive as of May 1999 with a median follow-up of 1574 days post-transplant. The patients transplanted with BM had faster engraftment and lower rates of graft-versus-host disease, 100-day mortality and overall mortality. HLA-matched sibling BM is preferred as a source but transplantation using unrelated UCB is still an option in treating pediatric bone marrow failure syndromes.
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PMID:Hematopoietic stem-cell transplantation using unrelated cord-blood versus matched sibling marrow in pediatric bone marrow failure syndrome: one center's experience. 1056 77

Successful engraftment of hematopoietic stem cells requires a supportive hematopoietic stromal microenvironment (HSM). Defects in the HSM associated with aplastic anemia, myelofibrosis, or caused by intensive ionizing radiation and chemotherapy generally result in failure of bone marrow (BM) engraftment. Transplantation of donor BM within donor HSM may therefore provide optimal conditions for allogeneic BM transplantation. We have transplanted donor hematopoietic cells together with their own HSM to improve acceptance of allogeneic or xenogeneic BM. The non-myeloablative treatment used induced tolerance to murine allografts and provided conditions for the life-long acceptance of allogeneic HSM. Allogeneic BM transplanted within it's own HSM under the kidney capsule caused less graft-versus-host disease than BM transplanted i.v. Tolerance in mice to xenogeneic (rat) HSM was less complete. Ectopic ossicles were small and contained fewer hematopoietic cells. However, simultaneous transplantation of rat BM and HSM to preconditioned mice improved engraftment of rat BM compared with transplantation of BM alone. Donor hematopoietic cells survived longer on their own HSM than on HSM of recipients.
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PMID:Transplantation of allogeneic or xenogeneic bone marrow within the donor stromal microenvironment. 1057 77

A 54-year-old man showed evidence of disease progression and a reduction in donor chimaerism by molecular microsatellite analysis 6 months after an allogeneic peripheral blood stem cell transplant for chronic idiopathic myelofibrosis. He was treated with a single infusion of donor leucocyte infusions (DLI), which led to the development of mild acute graft versus host disease (GVHD) and the rapid restoration of full donor haemopoiesis. This subsequently led to a progressive reduction in marrow fibrosis from grade IV to grade I over the following 6 months. We believe that this is the first report to provide clear evidence for the efficacy of DLI in this setting, which also provides evidence for the existence of a T-cell-mediated 'graft vs. myelofibrosis' effect similar to that seen against other haematological malignancies.
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PMID:Induction of remission after donor leucocyte infusion for the treatment of relapsed chronic idiopathic myelofibrosis following allogeneic transplantation: evidence for a 'graft vs. myelofibrosis' effect. 1069 77

A retrospective single center study was performed on 516 trephine biopsies derived from 160 patients with stable phase Ph+-CML and allogeneic BMT. Following morphometric quantification of reticulin-collagen fibers we tried to elucidate (1) the dynamics of bone marrow fibrosis in the post-transplant period; and (2) the influence of manifest myelofibrosis on relevant engraftment parameters. An evaluation of fiber density at standardized endpoints after BMT was carried out on a selected cohort of 124 patients (399 biopsy specimens). A manifest myelofibrosis (more than a three-fold increase compared to the normal fiber content) before BMT was found in 26% of our patients. Concentrating on bone marrow areas with reconstituting hematopoiesis, several findings emerged. Pretransplant myelofibrosis was associated with an initial regression following BMT, but insidiously recurred in the areas of regenerating hematopoiesis or developed in a few patients without increased pregraft fibers during the post-transplant period (mean observation time more than 4 months). Severe acute GVHD (grades III and IV) was significantly correlated with a greater amount of reticulin fibers in the early post-transplant period (9 to 30 days after BMT). Regarding engraftment parameters, a significant delay was detectable in the time to achieve transfusion independence for the patients with manifest myelofibrosis compared to those without pre-transplant fiber increase.
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PMID:Relevance and dynamics of myelofibrosis regarding hematopoietic reconstitution after allogeneic bone marrow transplantation in chronic myelogenous leukemia--a single center experience on 160 patients. 1096 65

Three patients with myelofibrosis received allogeneic stem cell transplantation after a dose-reduced conditioning regimen of busulphan (8 mg/kg), fludarabine (180 mg/m2) and antithymocyte globulin (4 x 10 mg/kg). The median age at transplantation was 51 years (range 44-58). All patients engrafted with a leucocyte count > 1.0 x 10(9)/l after a median of 18 d (range 16-20). Grade II acute skin graft-versus-host disease (GvHD) occurred in one patient. One limited and one extensive chronic GvHD was observed. All patients achieved complete haematological remission. In one patient the fibrosis resolved completely 180 d post transplant. All patients are alive 126, 466 and 764 d after transplantation.
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PMID:Dose-reduced conditioning regimen followed by allogeneic stem cell transplantation in patients with myelofibrosis with myeloid metaplasia. 1243 57

We describe the course of 25 patients with myelofibrosis (MF) due to agnogenic myeloid metaplasia (n=19) or essential thrombocytosis (n=6) who underwent allogeneic stem cell transplantation (SCT) at one of two Canadian centers. The median age at transplantation was 48.7 (IQR 45.9-50.4) years and transplantation was carried out at a median of 10.7 (IQR 5.67-26.5) months after diagnosis. Granulocyte engraftment (absolute neutrophil count >0.5 x 109/l) occurred at a median of 20 days after transplantation for splenectomized patients, compared with 27.5 days for nonsplenectomized individuals (P=0.03). Increased risk of grade II-IV acute graft-versus-host disease (P=0.04) was noted in patients transplanted after splenectomy. Patients with MF received 0.264+/-0.189 U of packed red blood cells per day over the first 180 days after transplantation, and remained dependent on red blood cell transfusions for a median of 123 (IQR 48-205) days. Complete remission of MF was documented in 33% of evaluable patients. The 1 year cumulative nonrelapse mortality was 48.3%. Median survival for this group of patients was 393 (IQR 109-1014+) days, with a projected 2-year overall survival of 41%. We conclude that allogeneic SCT offers a reasonable chance for prolonged survival in patients with advanced MF, but this occurs at the cost of considerable toxicity and nonrelapse mortality.
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PMID:Stem cell transplantation for myelofibrosis: a report from two Canadian centers. 1281 76

Within the past years, reduced or modified doses of chemotherapy or radiotherapy have been widely studied for conditioning before allogeneic hematopoietic cell transplantation in patients with myeloid leukemia not eligible for conventional transplantation. The main goal was to reduce the substantial treatment-related mortality in this patient population while preserving the potential curative graft-versus-leukemia effect. This review summarizes results of published trials using reduced-intensity conditioning (RIC) in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), and myelofibrosis. In most of the published trials conditioning contained fludarabine (90-180 mg/m(2)) in combination with busulfan (4 x 10 mg/kg), melphalan (90-140 mg/m(2)), or 2-5 Gy total body irradiation (TBI). Peripheral blood hematopoietic stem cells from related or unrelated donors were used as graft source in most of the studies. Post-transplantation immunosuppression consisted of cyclosporine combined with methotrexate or mycophenolate mofetil. Although the majority of the patients were above the age of 50 years, early treatment-related mortality was rather low. Nevertheless, the rate of clinically significant graft-versus-host disease (GVHD) seemed to be comparable to conventional transplants in most of the protocols. The outcome differed between trials, but diagnosis and disease status pre-transplant significantly influenced outcome. In summary, this approach is feasible and provides access to the curative potential of allogeneic stem cell transplantation for patients with higher age or comorbidities. Since the majority of the reports included heterogeneous patient populations, mostly with a short follow-up, more and specifically randomized studies are needed to define the role of RIC before allogeneic hematopoietic cell transplantation.
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PMID:Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation in myeloid diseases. 1291 Mar 73


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