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)

Bone marrow transplant recipients remain at risk for infections for a variable period of time even after adequate hematologic reconstitution. Late infections are a significant cause of morbidity and can be fatal in 4-15% of these patients. Patients with chronic graft versus host disease (GVHD) and unrelated-donor transplant recipients, even without GVHD, are at particular risk. Most late infections occur in the first post-transplant year, the majority are caused by bacteria, particularly encapsulated organisms, or herpes group viruses (CMV and VZV) and present with cutaneous, sino-pulmonary or systemic involvement. Effective chemoprophylaxis is available only for the encapsulated bacteria (penicillin or erythromycin) and Pneumocystis carinii (trimethoprimsulfamethoxazole). Routine use of long-term I.V. immunoglobulin supplementation has not been shown to be effective and may be harmful as it may delay reconstitution of humoral immunity. Active immunization (pneumococcal vaccine, influenza vaccine and HiB) can be effective in patients more than 6-12 months from transplant who do not have GVHD. In this review we present our experience, a summary of published literature on the subject of late infections in bone marrow transplant patients and offer guidelines for preventative strategies.
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PMID:Late infections following allogeneic bone marrow transplantation: suggested strategies for prophylaxis. 925 Jul 82

While effectively preventing graft-versus-host disease (GVHD), ex vivo T-lymphocyte depletion of the graft unfortunately increases graft rejection and reduces the graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation. The ex vivo transfer of the herpes-simplex thymidine-kinase (HS-tk) suicide gene into T-cells before their infusion with the hematopoietic stem cells, should allow for selective in vivo depletion of these T-cells with ganciclovir (GCV), if subsequent GVHD was to occur. We have demonstrated that retroviral-mediated transfer of HS-tk and Neomycine resistance genes in T-lymphocytes, followed by G418 selection, results in T-cells specifically inhibited by GCV with no bystander effect. In a phase I study, escalating amounts of HS-tk expressing T-cells are infused in conjunction with a T-cell depleted marrow graft to allogeneic HLA identical recipients. Toxicity, survival alloreactivity and GCV-sensitivity of the gene-modified cells are monitored.
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PMID:[Modulation of alloreactivity using genetically modified T lymphocytes]. 926 85

Reactivation of infections with herpes viruses is a frequent and major cause of morbidity after bone marrow transplantation. In this case report we stress that HSV infections of the colon and small intestine should be considered in the differential diagnosis of diarrhea and intestinal bleeding in the early post-transplantation period. Severe acute GVHD and subsequent intensive immunosuppressive treatment may increase the risk for reactivation of HSV infection particularly in situations in which acyclovir prophylaxis has been omitted.
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PMID:Herpes simplex infection of the jejunum occurring in the early post-transplantation period. 942 80

This study will evaluate the safety and efficacy of allogenic donor lymphocyte infusions in patients who have relapsed hematologic malignancies after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease (GvHD). We hypothesize that a retroviral vector containing the Herpes simplex thymidine kinase (HStk) gene will allow for retention of the anti-leukemia response of transfused donor lymphocytes while allowing for the adverse effects of GVHD to be mitigated. Patients with relapsed hematologic malignancies after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The Herpes Simplex thymidine kinase (HStk) gene will be transduced into the cells ex vivo using LTKOSN. 1 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effect of graft versus host disease, if it develops.
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PMID:Adoptive immunotherapy for leukemia: donor lymphocytes transduced with the herpes simplex thymidine kinase gene for remission induction. HGTRI 0103. 945 47

We examined five children who underwent allogeneic peripheral stem cell transplantation (PSCT) using positively selected CD34+ cells from three or two loci-mismatched donors. CD34+ cells mobilized from peripheral blood were separated by immunomagnetic beads. CD34+ cells at 2.2-6.2 x 10(6)/kg were transplanted into three patients with refractory leukemia, a patient with relapsed medulloblastoma and a patient with Fanconi's anemia following a conditioning regimen which included irradiation, alkylating agents and antithymocyte globulin treatment. The number of infused CD3+ cells included in grafts was 2.3-22.7 x 10(4)/kg. Four patients achieved engraftment and hematopoietic reconstitution (> 5 x 10(8)/l of neutrophils on day 10 or 11). Graft rejection was observed in the patient with Fanconi's anemia, but a rapid engraftment was obtained after second PSCT. Although no prophylactic agents other than ATG (included in the conditioning regimen) were used, greater than grade I acute GVHD was not observed, but limited chronic GVHD was observed in two patients. The two patients with leukemia relapsed on days 103 and 210, respectively, and the patient with medulloblastoma died of disease on day 159. The patient with Fanconi's anemia died of fungal infection. CMV and HHV-6 diseases developed in four and two patients, respectively. Thus, although SCT using positively selected peripheral CD34+ cells may be an alternative approach for overcoming graft rejection and GVHD from HLA- mismatched donors, persistent immune deficiency attributing to extremely low numbers of T cells in grafts can potentially lead to reactivation of herpes viruses.
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PMID:Allogeneic peripheral stem cell transplantation using positively selected CD34+ cells from HLA-mismatched donors. 950 68

Three hundred and six patients with low- and intermediate-risk leukaemias undergoing allogeneic BMT between 1980 and March 1996 were studied regarding transplantation-related mortality (TRM), relapse, and leukaemia-free survival (LFS). Among the patients were 262 recipients of marrow from HLA-identical siblings and 44 patients receiving marrow from HLA-A, -B, and -DR identical unrelated donors. Between 1986 and 1993, 153 adult patients received ciprofloxacin continuously during Cy conditioning, but since November 1993 ciprofloxacin has not been given until after Cy treatment. TRM at 5 yr showed an incidence of 30%. Significant risk factors in Cox regression multivariate analysis comprised acute GVHD grades II-IV (p < 0.0001), seropositivity for 3-4 herpes viruses prior to BMT (p = 0.002), intermediate risk disease (p = 0.008), female donor to male recipient (p = 0.015), and a donor age over 17 yr (p = 0.025). The risk of relapse was studied from 90 d after BMT, and the overall 5-yr incidence was 32%. Significant risk factors comprised acute leukaemia, as compared to CML (p = 0.003), total body irradiation (TBI) compared to busulphan treatment (p = 0.011), gram-negative prophylaxis with ciprofloxacin during cyclophosphamide (Cy) conditioning (p = 0.024), GVHD prophylaxis using a combination of methotrexate (MTX) and cyclosporine (CSA), compared to monotherapy (p = 0.037) and absence of chronic GVHD (p = 0.050). The 5-yr probability of relapse in patients receiving ciprofloxacin prophylaxis during Cy conditioning was 40%, compared to 24% in patients not receiving this treatment (p = 0.01). Overall, LFS at 5 yr was 49%. LFS was evaluated from day 30 after BMT until relapse or death of the patient. We found no difference in TRM, relapse or LFS between recipients of HLA-identical sibling or unrelated bone marrow, risk factors significantly associated with an inferior LFS included acute GVHD grades II-IV (p = 0.0002), intermediate risk disease (p = 0.003), donor seropositivity for 3-4 herpes viruses (p = 0.046), and TBI conditioning (p = 0.048).
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PMID:Risk factors in bone marrow transplant recipients with leukaemia. Increased relapse risk in patients treated with ciprofloxacin for gut decontamination. 957 94

We report our experiences with HLA-matched unrelated bonemarrow transplantation combining a preconditioning regimen of cyclophosphamide, antithymocyte globulin (ATG), and total body irradiation for two patients with severe aplastic anemia (SAA) who had already undergone repeated blood transfusions. Short-term methotrexate and cyclosporine were administered for graft-versus-host disease (GVHD) prophylaxis. Both patients achieved rapid engraftment within 3 weeks, furthermore, neither acute nor chronic GVHD developed. Our conditioning regimen appeared to be well-suited for unrelated bone marrow transplantation in heavily transfused SAA patients. However, both patients experienced bouts of fever about 20-30 and 40-50 days after transplantation, and it was difficult to differentiate whether they were affected by acute GVHD, cytomegalovirus (CMV) infections, or serum sickness. Because weakly positive CMV antigenemia was detected, both patients were given ganciclovir. Although their fever did not respond initially, it gradually subsided following the combined administration of prednisolone. These outcomes suggest it is essential that attention be devoted to the potential for serum sickness and the high risk of herpes virus infections, particularly by CMV, following the use of intensive preconditioning regimens that include ATG.
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PMID:[Unrelated bone marrow transplantation in two severe aplastic anemia patients preconditioned with a regimen of cyclophosphamide, antithymocyte globulin, and total body irradiation]. 1022 28

T-cell depletion (TCD) of the bone marrow graft remains the most effective method to prevent severe graft versus host disease after allogeneic bone marrow transplantation. Early studies of HLA-identical sibling transplants showed that although T-cell depletion decreased GVHD, T-cell depleted transplants had higher risks of graft failure and leukemia relapse, leukemia free survival (LFS) was not improved compared to non-T-cell depleted transplants. In order to avoid graft failure and increased risk of relapse associated with this approach, we initiated a pilot study of T-cell depletion of the marrow graft combined with reinfusion of a fixed quantity of CD2+ peripheral blood T-cells. Depletion technique consisted in negative purging using CD2 and CD7 monoclonal antibodies (MoAbs) followed by rabbit complement cytolysis. This approach was associated with an intensified conditioning regimen using total body irradiation, high-dose cytosine arabinoside and melphalan (TAM) for all but one patient. Twenty-one patients were included with a mean age of 40 years. Only one acute severe Graft Versus Host Disease (GVHD) was observed and all patients engrafted. At 63 months, probability of survival is 42.86% with a relapse risk of 19.89%, two patients died from B-cell lymphoproliferative disease, seven other died from the procedure partially because of the use of the TAM as pretransplant regimen. This approach is being pursued by a gene therapy trial using herpes-simplex - 1 thymidine kinase gene expressing peripheral donor T-cells.
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PMID:Low dose T-cell lymphocyte infusion combined with marrow T-cell depletion as prophylaxis of acute graft vs host disease for HLA identical sibling bone marrow transplantation. 1034 50

We report on a 19-month-old boy with refractory T-cell acute lymphoblastic leukemia who underwent allogeneic peripheral blood stem cell transplantation using positively selected CD34 cells from his HLA two-loci mismatched mother. The conditioning regimen consisted of busulfan (140 mg/m2/d for 2 days), total body irradiation (12 Gy) and melphalan (210 mg/m2). The patient received cyclosporin A for graft-versus-host disease (GVHD) prophylaxis. The CD34-positive cells were separated using an immunomagnetic cell-separation system (Isolex 50). The number of infused CD34-positive cells was 4.4 x 10(6)/kg. Successful engraftment was confirmed on day 14 by fluorescent in situ hybridization of X chromosomes. The patient experienced severe diarrhea due to thrombotic microangiopathy (TMA) following acute GVHD, and died on day 71 of human herpes virus type 6 pneumonitis. Stem cell transplantation using CD34 positively selected cells from HLA-mismatched related donors may be a useful treatment with low incidence of severe GVHD, but many problems remain to be overcome, including severe viral infections and TMA.
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PMID:[Infantile T cell acute lymphoblastic leukemia complicated by thrombotic microangiopathy and human herpes virus 6 infection after allogeneic peripheral blood stem cell transplantation using CD34-positive cells]. 1048 41

Human herpesvirus-6 (HHV-6), like all the other herpes viruses, remains latent in host cells after primary infection but can be reactivated in immunocompromised patients causing fever, skin rash, bone marrow (BM) suppression, pneumonitis, sinusitis and meningoencephalitis. We describe the case of a man with chronic myelogenous leukemia who developed encephalitis associated with acute graft-versus-host disease two months after a T-cell-depleted mismatched peripheral blood stem cell transplant. Magnetic resonance images of the brain revealed multiple bilateral foci of signal abnormality. HHV-6 was the only pathogen detected in cerebrospinal fluid by PCR. Treatment with both ganciclovir and foscarnet was unsuccessful and the patient gradually deteriorated and died. Other cases of HHV-6 encephalitis after bone marrow transplantation are reviewed.
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PMID:Fatal herpesvirus-6 encephalitis in a recipient of a T-cell-depleted peripheral blood stem cell transplant from a 3-loci mismatched related donor. 1062 99


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