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)

Fungal infections are currently a leading cause of infectious morbidity and mortality in patients undergoing allogeneic blood and marrow transplantation (BMT). Although the introduction of azole antifungals for prophylaxis has had a significant impact on the incidence of candidal infections (especially those caused by C. albicans and C. tropicalis), invasive aspergillosis has increased in incidence in many centers worldwide. Given the long risk period corresponding with graft-versus-host disease, and the toxicities of currently available mold-active antifungals, the development of a prevention strategy for these angioinvasive molds remains a challenge. The introduction of new antifungal drugs and adjunctive therapy to improve immune function may be beneficial in decreasing mortality associated with these infections in the future. Most importantly, a greater understanding of the pathogenesis of fungal disease and specific host risks is necessary to impact this increasingly important infection in immunocompromised hosts.
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PMID:Fungal infections in patients undergoing blood and marrow transplantation. 1142 95

The clinical results in 107 patients receiving a peripheral blood stem cell (PBSC) graft mobilized by granulocyte colony-stimulating factor (G-CSF) from HLA-A, -B, and -DR-compatible unrelated donors were compared to 107 matched controls receiving unrelated bone marrow (BM) transplants. Engraftment was achieved in 94% of the patients in both groups. The PBSC graft contained significantly more nucleated cells, CD34(+), CD3(+), and CD56(+) cells (P <.001), and resulted in a significantly shorter time-to-neutrophil (15 versus 19 days) and platelet engraftment (20 versus 27 days), compared to the BM control group (P <.001). Probabilities of acute graft-versus-host disease (GVHD) grades II to IV were 35% and 32% (not significant [NS]) and of chronic GVHD 61% and 76% (NS) in the PBSC and BM groups, respectively. There was no difference between the 2 groups in bacteremia, cytomegalovirus reactivation or disease, and fungal infection. The 3-year transplant-related mortality (TRM) rates were 42% in the PBSC group and 31% in the BM controls (P =.7) and the survival rates were 46% and 51%, respectively. The probability of relapse was 25% and 31% in both groups (NS), resulting in disease-free survival rates of 43% in the PBSC group and 46% in the BM controls (NS). In the multivariate analysis, early disease, acute GVHD grade 0 to I, and presence of chronic GVHD were independent factors associated with a better disease-free survival in this study. PBSC from HLA-compatible unrelated donors can be used safely as an alternative to BM for stem cell transplantation.
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PMID:No difference in graft-versus-host disease, relapse, and survival comparing peripheral stem cells to bone marrow using unrelated donors. 1153 6

We investigated the feasibility and efficacy of a fludarabine-based dose-reduced conditioning regimen followed by stem cell transplantation from related (n = 5) or unrelated HLA-matched donors (n = 7) in 12 patients with high risk MDS, who were not eligible for a standard myeloablative conditioning regimen. The conditioning regimen consisted of fludarabine 30 mg/m(2) daily for 6 days, busulfan 4 mg/kg daily for 2 days and anti-thymocyte globulin (ATG, rabbit) 10 mg/kg daily for 4 days in 11 patients, while one patient received fludarabine, ATG, cyclophosphamide and thiotepa. Graft-versus-host disease prophylaxis consisted of cyclosporine and a short course of methotrexate. The median age of the patients was 53 years (range 37-59). The median percentage of blasts in bone marrow aspirate at transplantation was 15% (range <5% to 35%). Diagnosis at transplant was RA (n = 1), RAEB (n = 5), RAEB-T (n = 5) and sAML (n = 1). A complex karyotype including monosomy 7 was noted in five patients. The reasons for using a dose-reduced conditioning regimen were prior autologous/syngeneic BMT (n = 4), active fungal infection (n = 2) or age/reduced performance status (n = 6). Engraftment was observed in all patients with complete donor chimerism. The incidence of acute GVHD (grade II-IV) was 33%. Eight patients died during follow-up due to relapse (n = 4), liver toxicity (n = 2), aspergillus (n = 1) or aGVHD grade IV (n = 1). After a median follow-up of 19 months, the 2-year estimated disease-free survival is 12% (95% CI: 2-23%) and the overall survival is 26% (95% CI: 4-52%). Fludarabine dose-reduced conditioning prior to allogeneic stem cell transplantation in high risk MDS patients, who were not eligible for standard transplantation, resulted in stable engraftment with complete chimerism, but the toxicity and relapse rate were considerable.
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PMID:A fludarabine-based dose-reduced conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors in patients with myelodysplastic syndrome. 1170 86

Patients receiving allogeneic bone marrow transplants are at risk of developing Aspergillus infections. The pre-transplant risk factors for the development of invasive disease include prolonged neutropenia, colonization with Aspergillus sp. or a prior history of fungal infection. Post-transplant risk factors include severe graft-versus-host disease with concomitant high-dose corticosteroid therapy, and colonization with Aspergillus sp. The antifungal prophylaxis of selected high-risk pre-transplant patients at the Royal Melbourne Hospital includes granulocyte transfusions and AmBisome. In high-risk patients post-engraftment, prophylaxis consists of oral itraconazole, or if it cannot be tolerated, AmBisome. Antifungal prophylaxis is discontinued upon resolution of neutropenia, when prednisolone dose falls below 10 mg/day or when Aspergillus colonization disappears. Following this regimen, there has been only one death due to fungal infection in over 80 consecutive allograft patients. This patient was infected with an amphotericin B-resistant organism.
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PMID:Prophylaxis and treatment of patients with aspergillosis: an overview, including the Royal Melbourne Hospital experience. 1180 86

Human herpesvirus 6 (HHV-6) infection is common in the general population. Primary infection occurs mainly in childhood, after which the virus establishes latency in the host and can be reactivated in immunocompromised individuals such as recipients of a solid organ or bone marrow transplant (BMT). HHV-6 infection occurs in 38--60% of BMT recipients and in 14--82% of solid organ recipients, usually 2--4 weeks post-transplantation. Two HHV-6 variants are recognized (HHV-6A and HHV-6B) and transplant patients are infected almost exclusively with variant B. Following BMT, the clinical diseases most commonly associated with HHV-6 infection are bone marrow suppression, interstitial pneumonitis, encephalitis and graft versus host disease. It has also been suggested that HHV-6 infection may be associated with fever and bone marrow suppression following liver transplantation and may contribute to rejection episodes after kidney transplantation. Infection with HHV-6 induces marked immunodepression, and an association both with cytomegalovirus disease and with fungal infection in transplant recipients has been reported. A direct causal relationship between HHV-6 infection and disease following transplantation, however, has yet to be proven conclusively.
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PMID:Post-transplant HHV-6 Diseases. 1186 97

Fungal infection is one of the most important causes of morbidity and mortality in bone marrow transplant (BMT) recipients. The growing incidence of these infections is related to several factors including prolonged granulocytopenia, use of broad-spectrum antibiotics, conditioning regimens, and use of immunosuppression to avoid graft-versus-host disease (GvHD). In the present series, we report five cases of invasive mold infections documented among 64 BMT recipients undergoing fluconazole antifungal prophylaxis: 1) A strain of Scedosporium prolificans was isolated from a skin lesion that developed on day +72 after BMT in a chronic myeloid leukemic patient. 2) Invasive pulmonary aspergillosis (Aspergillus fumigatus) was diagnosed on day +29 in a patient with a long period of hospitalization before being transplanted for severe aplastic anemia. 3) A tumoral lung lesion due to Rhizopus arrhizus (zygomycosis) was observed in a transplanted patient who presented severe chronic GvHD. 4) A tumoral lesion due to Aspergillus spp involving the 7th, 8th and 9th right ribs and local soft tissue was diagnosed in a BMT patient on day +110. 5) A patient with a history of Ph1-positive acute lymphocytic leukemia exhibited a cerebral lesion on day +477 after receiving a BMT during an episode of severe chronic GvHD. At that time, blood and spinal fluid cultures yielded Fusarium sp. Opportunistic infections due to fungi other than Candida spp are becoming a major problem among BMT patients receiving systemic antifungal prophylaxis with fluconazole.
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PMID:Fungal infections in marrow transplant recipients under antifungal prophylaxis with fluconazole. 1213 18

Invasive fungal infection is an increasing source of morbidity and mortality in patients with hematologic malignancies, particularly those with prolonged and severe neutropenia (absolute white blood cell count < 100/microL). Early diagnosis of invasive fungal infection is difficult, suggesting that antifungal prophylaxis could be the best approach for neutropenic patients undergoing intensive myelosuppressive chemotherapy. Consequently, antifungal prophylaxis has been extensively studied for more than 20 years. Nonabsorbable polyenes reduce superficial mycoses but are not effective in preventing or treating invasive fungal infections. Intravenous amphotericin B and the newer azoles were used in numerous clinical trials, but the value of antifungal prophylaxis in defined risk groups with cancer is still open to discussion. Recipients of allogeneic stem cell transplants and patients with a relapsed leukemia are high-risk patient populations. In addition, certain risk factors are well defined, for example, neutropenia more than 10 days, corticosteroid therapy, sustained immunosuppression, and graft-versus-host disease. In contrast to study efforts, evidence-based recommendations on the clinical use of antifungal prophylaxis according to risk groups are rare. The objective of this review of 50 studies accumulating more than 9000 patients is to assess evidence-based criteria with regard to the efficacy of antifungal prophylaxis in neutropenic cancer patients.
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PMID:Evidence-based assessment of primary antifungal prophylaxis in patients with hematologic malignancies. 1239 55

We made the hypothesis that donor and recipient gene polymorphisms that drive the host response to microorganisms could be associated with infections after bone marrow transplantation (BMT). HLA-identical BMT was performed for patients with acute (n = 39) or chronic leukemia (n = 68). Genotyping was performed in 107 D/R DNA pairs for gene polymorphisms of cytokines (tumor necrosis factor-alpha [TNF-alpha] and TNF-beta, interleukin-1 receptor antagonist [IL-1Ra], IL-6, and IL-10), adhesion molecules (CD31 and CD54), Fcgammareceptors (FcgammaRIIa, IIIa, IIIb), mannose-binding lectin (MBL), and myeloperoxidase (MPO). First infection (overall) and first episodes of bacterial, viral, or invasive fungal infection were studied retrospectively for 180 days after BMT. Univariate and multivariate analyses, using death as a competing event, were performed to study risk factors. In multivariate analysis, first overall infections were increased in patients with the FcgammaRIIa R-131 genotype (hazard ratio [HR] = 1.92; P =.04), and severe bacterial infections were increased when the MPO donor genotype was AG or AA (HR = 2.16; P =.03). Viral and invasive fungal infections were not influenced by any genetic factor studied. Interestingly, we also found that (1) time to neutrophil recovery was shorter when donors were FcgammaRIIIb HNA-1a/HNA-1b (HR = 1.77; P =.002); (2) donor IL-1Ra (absence of IL-1RN*2) increased the risk for acute graft-versus-host disease (GVHD) (II-IV) (HR = 2.17; P =.017); and (3) recipient IL-10 (GG) and IL-1Ra genotypes increased the risk for chronic GVHD (P =.03 and P =.03, respectively). Finally, 180-day transplantation-related mortality rates were increased when donors were FcgammaRIIIb HNA-1a/HNA-1a or HNA-1b/HNA-1b (HR = 2.57; P =.05) and donor MPO genotype was AA (HR = 5.14; P =.004). In conclusion, donor and recipient gene polymorphisms are informative genetic risk factors for selecting donor/recipient pairs and could help in the understanding of mechanisms involved in host defenses of BM transplant recipients.
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PMID:Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation. 1239 99

We investigated the efficacy of an antithymocyte globulin/cyclophosphamide preparative regimen prior to allogeneic stem cell transplantation from HLA-identical siblings in patients with severe aplastic anemia. Since 1990, 21 patients, 6 males and 15 females, with a median age of 25 years (range: 7-43) have been enrolled in the protocol consisting of 200 mg/kg cyclophosphamide and 90-120 mg/kg antithymocyte globulin (ATG, rabbit, Fresenius, Bad Homburg, Germany). For further graft-versus-host disease (GVHD) prophylaxis all patients received cyclosporin A and a short course of methotrexate (MTX). Only one patient had a primary graft failure (5%). All other patients engrafted with a leukocyte count >1.0 x 10(9)/l and a platelet count >20 x 10(9)/l after a median of 19 (range: 11-28) and 26 days (range: 13-67), respectively. No late graft failure or relapse was observed. Two patients experienced mild acute GVHD grade I (10%), and one patient developed grade II GVHD (5%). No severe grade III/IV GVHD was observed; 17% of the patients developed limited chronic GVHD. The treatment-related mortality was 14% and mainly due to fungal infection. After a median follow-up of 70 months (range: 2-139), the estimated overall and event-free survival at 10 years for all patients is 86% (95% confidence interval: 70-100%). We conclude that ATG plus cyclophosphamide is an effective conditioning regimen in patients with aplastic anemia undergoing stem cell transplantation with a low treatment-related mortality, resulting in an excellent outcome.
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PMID:Long-term follow-up of allogeneic stem cell transplantation in patients with severe aplastic anemia after conditioning with cyclophosphamide plus antithymocyte globulin. 1245

Systemic scedosporiasis due to the anamorph or asexual form Scedosporium apiospermum (Pseudallescheria boydii) has become an important cause of opportunistic mycosis, especially in patients undergoing high-risk hematopoietic stem cell transplantation. We report a case of rapidly progressive cerebellar hyalohyphomycosis due to Scedosporium apiospermum in an allogeneic marrow graft recipient receiving treatment for severe graft-versus-host disease. This fatal breakthrough intracranial abscess, due to amphotericin B-resistant (minimum inhibitory concentration > 16 micro g/ml) mold, developed during the course of systemic antifungal therapy given for multicentric pulmonary aspergillosis. Despite treatment with high-dose Abelcet (10 mg/kg daily), free amphotericin B was not detected in postmortem cerebellar tissue. A broad-spectrum triazole-based agent (voriconazole/UK-109, 496--Vfend), and a novel fungal cell wall inhibitor, an echinocandin/pneumocandin analog (caspofungin/MK-0991--Cancidas), which exhibit excellent in vitro activity against most clinical Pseudallescheria boydii-Scedosporium apiospermum isolates, have recently become available in the United States and may provide much needed treatment options for patients at risk.
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PMID:Breakthrough Scedosporium apiospermum (Pseudallescheria boydii) brain abscess during therapy for invasive pulmonary aspergillosis following high-risk allogeneic hematopoietic stem cell transplantation. Scedosporiasis and recent advances in antifungal therapy. 1253 65


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