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)

The use of hematopoietic growth factors after allogeneic bone marrow transplantation (BMT) was investigated either in a preclinical canine model or in patients. G-CSF administration in dogs after high-dose total body irradiation (TBI) and transplantation of DLA-identical littermate marrow significantly accelerated recovery of peripheral blood neutrophils, monocytes and lymphocytes, but not of platelet counts, without significantly increasing the risks of graft failure or graft-versus-host disease (GVHD). GM-CSF given to patients after HLA-identical sibling BMT was well tolerated at doses < or = 250 micrograms/m2/day and resulted in significantly faster neutrophil recovery compared with matched historical controls. Risks of graft failure, GVHD or relapse were not increased. When GM-CSF was given after matched or 1-antigen mismatched unrelated BMTs, the number of febrile days and septic episodes within the first 28 days was reduced even though neutrophil recovery was not accelerated. Incidences of graft failure, GVHD or relapse were not increased. In recipients of BMT with invasive fungal infections, M-CSF in combination with conventional anti-fungal therapy may have a beneficial effect on survival. Treatment with GM-CSF in patients with graft failure appears to result in improved survival without increasing the risks of GVHD or relapse.
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PMID:Hematopoietic growth factors after allogeneic marrow transplantation in animal studies and clinical trials. 772 31

G-CSF-mobilized peripheral blood progenitor cells (PBPC) were utilized in a patient who failed to engraft after an unmanipulated HLA-matched allogeneic bone marrow transplant. Marrow engraftment occurred after repeated conditioning with high-dose cyclophosphamide and PBPC infusion. Severe graft-versus-host disease (GVHD) developed shortly after marrow engraftment. The role of PBPC in allogeneic transplant, the associated potential risk of GVHD, and the necessity of reconditioning before stem cell reinfusion are discussed.
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PMID:Successful engraftment using allogeneic peripheral blood progenitor cells in a patient with primary bone marrow graft failure. 775 98

Most children with acute lymphoblastic leukemia (ALL) are successfully treated by chemotherapy. For those patients, who relapse on therapy, bone marrow transplantation (BMT) is considered most appropriate after a subsequent remission is achieved. Three boys with ALL aged from 9 to 13 years met these criteria and received BMT from their HLA-compatible sisters after marrow ablation with total body irradiation 12 Gy plus high dose cytosine arabinoside 3 gm/m2/12h x 12 doses and graft-versus-host disease (GVHD) prophylaxis with cyclosporine plus short course methotrexate from March 10, 1989 to May 23, 1992. Filgrastim (rhG-CSF) was used to hasten the recovery of granulocyte in one patient. All three patients got full engraftment and two had grade 1 acute GVHD. None of them developed chronic GVHD. Two patients have disease-free survival over 51 and 12 months respectively post BMT without further chemotherapy. One patient died of recurrent refractory leukemia 5 months after BMT. The toxicity of this conditioning regimen included photophobia, conjunctivitis and erythematous skin rashes. One patient who received filgrastim from day 1 to 21 developed severe bone pain. However, this patient had faster recovery of granulocyte count than the other two patients. The preliminary results of this work favors BMT for children with recurrent ALL whose ultimate survival is usually poor when treated with chemotherapy. Further efforts are necessary to investigate new methods for reducing leukemic relapse in ALL patients undergoing BMT.
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PMID:Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in second remission or relapse. 783 80

Peripheral blood stem cells (PBSCs) have been used rarely for allogeneic transplantation because of concerns regarding graft failure and graft-versus-host disease (GVHD). We evaluated the results of allogeneic PBSC transplantation (allo-PBSCT) in 9 patients with refractory leukemia or lymphoma receiving myeloablative therapy followed by allo-PBSCT from an HLA-identical sibling donor. Three patients had relapsed 11 to 21 months after allogeneic bone marrow transplantation (allo-BMT) and underwent allo-PBSCT using the same donor. Six patients received PBSCs as their initial allogeneic transplant. Filgrastim-mobilized PBSCs were collected from the donors in 3 to 4 aphereses and cryopreserved. The apheresis collections contained a median nucleated cell count of 16.5 x 10(8)/kg (range, 10.8 to 28.7 x 10(8), 10.7 x 10(6) CD34+ cells/kg (range, 7.5 to 22.5 x 10(6)), and 300.0 x 10(6) CD3+ cells/kg (range, 127.8 to 1,523.2 x 10(6)). The median recovery of CD34+ progenitor cells after freezing, thawing, and washing was 106.4% (range, 36.7% to 132.0%). All patients received filgrastim posttransplant through engraftment, and cyclosporine and methylprednisolone were used for GVHD prophylaxis. Neutrophil recovery to greater than 0.5 x 10(9)/L and greater than 1.0 x 10(9)/L occurred at a median of 9 (range, 8 to 10) and 9 days (range, 8 to 11) posttransplant, respectively, which was similar to historical controls after allo-BMT and granulocyte colony-stimulating factor therapy. Platelets recovered to greater than 20 x 10(9)/L and greater than 50 x 10(9)/L at a median of 12 (range, 8 to 25) and 15 days (range, 11 to 59), respectively, which was significantly more rapid than for the controls (P < .01). Donor cell engraftment was documented by cytogenetics, fluorescence in situ hybridization, and/or restriction fragment length polymorphisms with longest follow-up of 283 + days. Three patients developed grade 2 acute GVHD involving only the skin. Three of five evaluable patients show limited chronic GVHD. Cryopreserved, filgrastim-stimulated allogeneic PBSCs may be a suitable alternative to allogeneic marrow for transplantation with the advantage of more rapid platelet recovery. Acute GVHD was minimal despite the infusion of 1 log more CD3 cells than with marrow allografts. Further studies are required to assess long-term risks of chronic GVHD.
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PMID:Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma: potential advantage of blood over marrow allografts. 760 19

Thirty adults with hematologic malignancies at high-risk for relapse were treated on a phase I-II study of high-dose thiotepa, busulfan (BU) and cyclophosphamide (CY) as the preparative regimen for allogeneic marrow transplantation. Cyclosporine and methylprednisolone or anti-CD5 ricin A chain immunoconjugate were used as graft-versus-host disease prophylaxis. Filgrastim was given from day 1 to enhance engraftment. Median follow-up time is 16 months (range 9-29 months). Grades III-IV regimen-related toxicity occurred in 5 (26%) of 19 patients treated with thiotepa 250 mg/m2 x 3, BU 1 mg/kg x 12 and CY 60 mg/kg x 2 and this was considered the maximal tolerated dose-schedule. Stomatitis and hepatoxicity were dose-limiting. All patients engrafted and had complete donor chimerism. The actuarial rate of acute graft-versus-host disease was 71% (95% CI 62-80%). The relapse rate at 1 year was 38% (95% CI 25-50%) and the actuarial survival at 1 year was 30% (95% CI 22-38%). The combination of thiotepa, BU and CY is tolerable as a preparative regimen for allogeneic marrow transplantation.
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PMID:A phase I-II study of high-dose thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic marrow transplantation. 799 71

We describe a case of cold agglutinin disease (CAD) following allogeneic bone marrow transplantation. This 36-year-old male developed CAD 3 weeks after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Cyclosporin A and methotrexate had been administered to prevent graft-versus-host disease. Other agents administered included cytomegalovirus hyperimmune globulin and recombinant human G-CSF. Pericarditis preceded the development of CAD. The characterization of cold agglutinin (CA) was monoclonal IgM-kappa with anti-Pr antigen specificity, probably derived from the engrafted donor lymphocytes. The administration of prednisolone led to transient improvement. The CA titer decreased without further treatment 12 weeks after transplant.
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PMID:Cold agglutinin disease following allogeneic bone marrow transplantation. 819 73

A 5-year-old boy with severe aplastic anemia failed to respond to cyclosporine (CYA), prednisolone and antilymphocyte globulin (ALG). No suitable sibling marrow donor was available, but an HLA-matched unrelated donor was identified. The patient was conditioned with cyclophosphamide (CY), 50 mg/kg/day for 4 days, total nodal irradiation (8 Gy), and ALG 30 mg/kg/day for 3 days. GVHD prophylaxis consisted of daily CYA, methotrexate (MTX) and ALG. The patient failed to achieve sustained engraftment. He was reconditioned with high-dose prednisolone and anti-T lymphocyte monoclonal antibody OKT3. The boy was reinfused with the same donor marrow on day 0 (+49/first BMT). No GVHD prophylaxis was given the second time. He received G-CSF on days 0 to +20 after the second transplant. Full engraftment was achieved on day +16 (+65). However, on day +31 (80) he developed a biopsy-proven B cell lymphoproliferative disorder (BLPD). After the OKT3 administration was stopped and treatment with ganciclovir and high-dose immunoglobulin was initiated, the BLPD resolved and the patient was discharged on day +50 (99). He is currently well with a functioning graft 266 (305) days posttransplant, with no sign of GVHD.
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PMID:Remission of a lymphoproliferative disorder occurring after second BMT from an unrelated donor in a 5-year-old boy with severe aplastic anemia. 853 24

We describe the case of a 41-year-old female who underwent allogeneic blood cell transplantation with CD34(+)-enriched cells from an HLA-matched unrelated donor for AML in second CR. The conditioning regimen consisted of TBI (12 Gy), VP16 (1800 mg), cyclophosphamide (7200 mg), and ATG (7200 mg). GVHD prophylaxis consisted of CsA and a short course of MTX. Receiving G-CSF from day +1, engraftment occurred on day +19 after stem cell infusion. Starting on day +10, GVHD grade II (skin and liver) developed that responded to high-dose steroid therapy. The patient died on day +38 due to suspected cerebral aspergillus infection. This case demonstrates the feasibility of primary transplantation of CD34(+)-enriched allogeneic peripheral stem cells from a matched unrelated donor leading to engraftment of donor cells.
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PMID:Transplantation of allogeneic rhG-CSF mobilized peripheral CD34+ cells from an HLA-identical unrelated donor. 854 73

We examined whether the use of G-CSF would affect the outcome of allogeneic marrow transplantation in humans and mice. Retrospective analysis of 24 patients who had received allogeneic marrow grafts from HLA-identical siblings revealed that the incidence of chronic but not acute graft-versus-host disease (GVHD) was lower in the patients receiving G-CSF than in those not given G-CSF (18% vs. 80%, P = 0.02). There was a difference in serum TNF-alpha levels during the first 3 months after transplant between these two groups. Four out of the ten patients who were not given G-CSF showed elevated serum TNF-alpha levels, whereas there was only one patients with an increased TNF-alpha level among eleven patients who were given G-CSF. With the use of murine acute and chronic GVHD models, we also observed that administration of G-CSF improved the survival of minor GVHD, but not major GVHD, mice. Taken together, these findings suggest that G-CSF down-regulates allogeneic immune responses and is active in modulating alloreactivity in vivo.
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PMID:Modulation of allogeneic immune responses by filgrastim (recombinant human granulocyte colony-stimulating factor) in bone marrow transplantation. 858 69

In order to obtain an additional graft versus leukemia effect (GVL) and rapid engraftment, donor leukocyte infusion (DLI) was added to unseparated, sex-mismatched allogeneic bone marrow transplantation in two male patients (age 21, 26) affected by high risk hematological malignancies (refractory T-ALL, refractory B-LBL in leukemic phase). Graft versus host disease (GVHD) prophylaxis consisted of methotrexate (MTX) alone. DLI were obtained after G-CSF 16 ug/kg/day sc. A total of 2.36 and 5.8 x 10(6)/kg MNC, 5.4 and 11 x 10(6)/kg CD34+ cells, 1.3 and 1.3 x 10(6)/kg CD3+ lymphocytes, respectively, were infused. Hemopoietic recovery occurred promptly. Complete chimerism was detected by cytogenetic examination. One patient developed an extramedullary relapse that first involved the cranial nerves, and then the testes, soft tissue and skin; the other patient developed central nervous system disease and then bilateral paravertebral masses with progressive paraplegia. Despite complete medullary remission with normal female karyotype, both patients died from extramedullary progression of their disease. Our observation shows that, at least in high risk patients, no additional GVHD or GVL effect was evident after donor leukocyte infusion. Extramedullary relapse was not prevented despite good control of medullary disease.
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PMID:Extramedullary relapse after allogeneic bone marrow transplantation plus buffy-coat in two high risk patients. 864 54


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