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)

In our BMT Unit, we have observed a high frequency of skin rash associated with fever and other clinical findings during engraftment of autologous BM and/or PBSC. Thirty patients with breast cancer and 12 patients with Hodgkin's or non-Hodgkin's lymphoma, treated with the same regimen, were analyzed retrospectively or prospectively to characterize the clinical syndrome, its frequency, and its clinical course, as well as to define the factors affecting its incidence. In patients developing skin rash, the median and range for time to onset of skin rash and for time to increase in WBC after reinfusion of stem cells were identical (8 days, range 5-13) and did not differ significantly (P = 0.533). Twenty-three patients (55%) had skin rash, 18 patients had fever. Other, less frequent manifestations include platelet transfusion refractoriness (PTR), diarrhea, diffuse alveolar hemorrhage, and autoimmune thrombocytopenia or hemolytic anemia. A higher proportion of breast cancer patients developed the syndrome in comparison to lymphoma patients (67% vs 25%, P = 0.051). Acute GVHD grade I-II was established histologically in six patients with the syndrome. Comparison of the incidence of the syndrome by different variables using Fisher's exact test revealed significance for disease category (P = 0.02) and number of previous treatment regimens (P = 0.002) as predictive factors for developing the autoaggression syndrome. In other words, patients with breast cancer and those with only one previous treatment regimen were more likely to develop the syndrome. This study suggests that an autoaggression GVHD-like syndrome accompanies the early phase of autologous engraftment and that a higher frequency of the syndrome might be seen in breast cancer patients undergoing high-dose chemotherapy and autologous stem cell transplantation.
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PMID:Increased frequency of autoaggression syndrome associated with autologous stem cell transplantation in breast cancer patients. 911 5

Donor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone marrow transplantation (BMT). Severe graft-versus-host disease and prolonged periods of pancytopenia compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent some of the problems associated with DLI. Eleven patients (median age 41 years) received a total of 20 donor cell infusions. Their diagnosis was CML in hematological (two patients) or cytogenetic relapse (two patients), six patients suffered from acute myeloid leukemia (AM; n = 5) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+). One patient had multiple myeloma (MM). All six patients with acute leukemias received cytoreductive therapy prior to PBPC infusions; three patients with CML were pretreated with IFN alpha. Four of four patients with CML responded to PBPC infusions and currently are in complete clinical and molecular remission for time periods between 1 and 12 months. Six of six patients with acute leukemias achieved a complete remission. All of them relapsed after a median remission duration of 24 weeks (range 11-49 weeks). Three patients relapsed at extramedullary sites (CNS, testes, skin). Four of six acute leukemia patients received further cytoreductive therapy. All patients responded again and are in complete remission for time periods between 14 and 615 days. Two patients with acute leukemias have died due to dissemination of the disease. The patient with MM did not respond and is alive with disease. Severe (grade III) acute GVHD developed in two of 11 patients, three patients developed grade II disease, six patients did not show any signs of GVHD. Extensive chronic GVHD has developed in two cases to date. Patients with chemotherapy prior to PBPC infusion developed neutropenia and thrombocytopenia with a maximum duration of 20 and 14 days, respectively; prolonged periods of neutropenia did not occur. Two patients developed long-lasting thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted in only limited duration of cytopenia. The usage of PBPC infusion instead of non G-CSF-mobilized donor cells for treatment of relapse after BMT may reduce pancytopenia-related complications and merits further investigation.
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PMID:Allogeneic peripheral blood progenitor cells for treatment of relapse after bone marrow transplantation. 933 54

Allogeneic bone marrow transplantation (BMT) is an effective therapy for Fanconi's anemia (FA). However, mortality and transplant-related complications are usually high due to increased sensitivity to the alkylating agents and radiation commonly used for pre-transplant conditioning. Fludarabine monophosphate is a purine analogue that has been proven effective as a conditioning agent for chronic lymphocytic leukemia patients. We report a child with FA in leukemic transformation with thrombocytopenia and 20% myeloblasts who underwent successful BMT following conditioning with fludarabine/ATG/cyclophosphamide. The regimen was well tolerated, no transplant-related complications were observed, and engraftment was rapid. The child is currently 10 months post-BMT, in excellent clinical condition with a normal blood count, 100% chimerism and no sign of graft-versus-host disease (GVHD). We suggest that this fludarabine-based regimen may be effective in the conditioning of standard, as well as transforming, FA patients for BMT.
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PMID:A fludarabine-based protocol for bone marrow transplantation in Fanconi's anemia. 946 88

Pluripotent stem cells of hematopoiesis are included among CD34+ cells in the blood and bone marrow. After granulocyte-colony stimulating factor (G-CSF) mobilization, 1-2% of the mononuclear cells in the blood are CD34+ cells, which can be obtained by leukapheresis. We performed CD34+ progenitor cell transplantation in two children with severe aplastic anemia (SAA) who lacked HLA-matched donors. The donors were treated with G-CSF, 600 micrograms/body/day subcutaneously, for 4-5 days. CD34+ cell selection was performed from the apheresis concentrate with mouse anti-CD34 antibody 9C5 and magnet beads coated with sheep anti-mouse IgG1. After the transplantation, the patients received tacrolimus to prevent graft-versus-host disease (GVHD). G-CSF was given to both patients. A mean number of 4.96 x 10(6) CD34+ cells per kilogram of body weight were transplanted. The hematopoietic recovery after the CD34+ cell transplantation was rapid, except for platelets, and acute GVHD was less than or equal to grade I. Case 1, who demonstrated mixed chimerism, anemia and thrombocytopenia after the graft, received a second transplant with intensified preconditioning, and now sustains complete and stable hematopoiesis after a follow-up of 314 days posttransplant. Although Case 2 showed early rejection and received a second transplant, sustained engraftment was never achieved. However, the patient's own hematopoiesis appeared. For SAA patients who do not have HLA-matched donors, this type of approach seems to be a feasible and useful method. However, an intensified preconditioning regimen to overcome the high likelihood of rejection should be employed.
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PMID:CD34+ progenitor cell transplantation from two HLA-mismatched healthy fathers to two infants with severe aplastic anemia. 959 40

Children with severe combined immunodeficiency (SCID) have profoundly diminished humoral and cellular immunity resulting in death during infancy unless immune reconstitution occurs by bone marrow transplantation (BMT). Thrombocytopenia post-bone marrow transplantation can be seen in relation to infection, graft-versus-host disease (GVHD) and rarely, as an autoimmune phenomenon due to immune dysregulation. We report two cases of severe AITP following BMT for SCID. Both cases developed large intracerebral hemorrhages from which one died. Autoimmune thrombocytopenia in this setting can be life-threatening and we recommend early and active intervention.
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PMID:Acquired autoimmune thrombocytopenia post-bone marrow transplantation for severe combined immunodeficiency. 960 13

Acute intestinal graft-versus-host disease (GVHD) develops in about 30-50% of allogeneic bone-marrow transplant recipients: 10-20% have gastrointestinal emergencies (hemorrhage or perforation). Mortality reaches 30-60% in patients with acute, grade 2-4 GVHD. We studied 36 bone marrow recipients in whom acute intestinal GVHD developed. Seven had gastrointestinal emergencies: 4 severe gastrointestinal bleeding and 3 acute peritonitis. Three patients with gastrointestinal bleeding and one patient with peritonitis responded to medical therapy. Three needed surgery: one with bleeding and two with peritonitis, while 1 patient had embolization. Of the 7, two patients died, one after embolization and one after surgery. Two of the three surgically-treated cases are still alive several years after operation. From this experience we feel that surgery for gastrointestinal bleeding in acute GVHD is indicated only when medical treatment fails. Severe neutropenia, thrombocytopenia (<10.000 x mm3) and blood cultures positive for CMV have an unfavorable prognostic value.
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PMID:Gastrointestinal emergencies in patients with acute intestinal graft-versus-host disease. 963 82

The efficacy and safety of mycophenolate mofetil (MMF) in combination with CsA and prednisolone for the treatment of acute and chronic GVHD (aGVHD and cGVHD, respectively) after BMT and PBSCT from HLA-mismatched and -matched donors was evaluated in an open single center trial. Twenty-four patients, 17-48 years of age, with acute (n = 17) and chronic GVHD (n = 7) were treated with 2 g MMF daily in addition to CsA and prednisolone. Overall grade improvement of aGVHD was found in 11 of 17 (65%) patients treated with MMF. MMF therapy in the treatment of cGVHD led to moderate improvement in three of six patients with limited cGVHD. The most common adverse hematologic events of MMF were leukopenia (n = 6), anemia (n = 4) and thrombocytopenia (n = 3). Hematological adverse events were not severe and did not require the discontinuation of MMF. In this preliminary study, we have shown that MMF can be used safely for the treatment of aGVHD. In addition, the MMF therapy resulted in significant dose reduction of prednisolone for the treatment of GVHD.
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PMID:Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. 1122 81

One hundred and thirteen patients who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic uremic syndrome (HUS). HUS developed in seven patients (four males and three females, five acute lymphocytic leukemia (ALL), one acute myelogenous leukemia, one non-Hodgkin's lymphoma) between 36-196 days after BMT. Four patients were recipients of autologous BMT and three were those of allogeneic BMT. Six patients were preconditioned with the regimens including fractionated total body irradiation (TBI). ALL and preconditioning regimen with TBI were suspected to be the risk factors for the development of HUS. Cyclosporin A (CSP) administration was discontinued in three patients who had been given CSP for graft-versus-host disease prophylaxis. Predonisolone was given to the three patients and plasma exchange was performed in one patient. Both hemolytic anemia and thrombocytopenia were resolved in virtually all patients, while creatinine elevation has persisted along with hypertension in one patient.
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PMID:[Hemolytic uremic syndrome after bone marrow transplantation]. 969 69

Thrombotic complications are observed in patients undergoing bone marrow transplantation despite thrombocytopenia and impaired coagulation due to liver function disturbances. Endothelial cell damage which is involved in the pathogenesis of major transplant related complications like graft-versus-host disease, veno-occlusive disease, sepsis or microangiopathy may be a contributing factor. Little is known about platelet function in bone marrow transplant recipients. In order to study functional alterations in circulating platelets we investigated unstimulated and ADP-stimulated platelets of 10 bone marrow transplant recipients ex vivo by flow cytometry in a pilot study using a panel of monoclonal antibodies to characterize changes in membrane glycoproteins. Samples were collected before and during conditioning and at three timepoints after engraftment. 10 healthy volunteers served as controls. Platelets of bone marrow transplant recipients showed partly a significant, higher expression of surface bound fibrinogen, activated fibrinogen receptor, and glycoprotein Ib as compared to controls. P-selectin, a marker of platelet degranulation was significantly elevated after ADP-induced stimulation at all timepoints compared to controls. Only marginal differences were found for GP IIb/IIIa surface expression. The data point to an increased platelet activation state in bone marrow transplant recipients which might contribute to the thrombotic phenomena observed in these patients.
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PMID:Changes in platelet membrane glycoproteins before bone marrow transplantation and after engraftment--a pilot study. 975 3

Acute graft-versus-host disease (GVHD) remains the major obstacle for successful allogeneic bone marrow transplantation (BMT). The frequency of grade II or higher acute GVHD ranges from 30-50% in human leukocyte antigen (HLA)-matched sibling transplants and 50-80% in HLA-matched unrelated transplants. The mortality and morbidity associated with this complication are substantial. Corticosteroid and polyclonal antibodies such as antithymocyte globulin (ATG) have had little success in treating the disease; however, advances have been made in hybridoma technology and understanding its immunopathophysiology. Based on these new insights, monoclonal antibodies, either murine or "humanized," were tested as rescue treatment for acute GVHD in human trials. Complete response rates ranged from 20-40%, with relapse occurring often. Side effects consisted of constitutional symptoms such as fever, chills, hypotension, thrombocytopenia, and leukopenia. Limitations of monoclonal antibody treatment included low response rate and patient survival, high relapse rate, risk of infectious complication, and leukemic relapse. Future study should focus not only on improved side effects and efficacy of monoclonal antibodies but also on better patient survival.
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PMID:Monoclonal antibodies in the treatment of steroid-resistant acute graft-versus-host disease. 975 10


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