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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infections are an almost inevitable complication of human bone marrow transplantation and account for the majority of deaths in transplant recipients. Even prior to the initiation of the transplantation procedure, patients may present with infections complicating previously unsuccessful chemotherapy for hematological malignancy or aplastic anemia. Nevertheless, these pre-transplantation infections should not exclude the possibility of bone marrow transplantation if they can be successfully controlled with specific antimicrobial therapy and necessary adjunctive measures. The immediate post-transplantation period prior to engraftment is characterized by severe marrow aplasia that results from high-dose chemotherapy and total-body irradiation. Infections are primarily septicemias and localized processes caused by bacteria and fungi and their incidence increases as the intensity of immunosuppression is escalated. The high mortality associated with bacterial septicemia makes early, empirical antibacterial therapy mandatory. However, the reduction in mortality from bacterial infection resulting from such an aggressive approach may be offset by a higher mortality from invasive fungal infection, especially in patients with prior fungal colonization and undergoing prolonged conditioning therapy. Thus, until more specific and sensitive tests for the diagnosis of invasive fungal infection become available, empirical intravenous amphotericin should be considered in patients who are persistently febrile and deteriorate clinically in the face of appropriate antibacterial therapy. Interstitial pneumonia associated with severe GVHD is the major infectious complication after successful marrow engraftment and is the most significant barrier to long-term survival. Trimethoprim-sulfamethoxazole is effective prophylaxis against interstitial pneumonia due to Pneumocystis carinii, but one half of the patients still develop a pneumonitis either associated with CMV or of unknown etiology. Mortality from interstitial pneumonia is related to prior radiation therapy while survival is associated with a four-fold rise in CMV CF antibody titer. The latter observation supports the need to investigate passive immunization with CMV antibody as a means of preventing some interstitial pneumonias. Despite the progress made in many areas of human bone marrow transplantation, the majority of graft recipients still die of infectious complications. Thus, new approaches to the management of infections in transplant recipients are urgently needed. Better-tolerated oral nonabsorbable antibiotics, laminar-air-flow rooms, granulocyte transfusions, and chemotherapy and immunotherapy for CMV are among the prophylactic and therapeutic measures that must be critically evaluated in well-controlled, prospective studies. Continued assessment of the infectious complications of bone marrow transplantation is a critical aspect of any ongoing transplant program, not just a research goal...
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PMID:Infectious complications of human bone marrow transplantation. 36 7

Recovery from acquired aplastic anemia associated with hepatitis is rare. This case of a 6-year-old boy with severe aplastic anemia is the first reported association of this disease with a hepatitis A infection. Antibody to hepatitis A (anti-HA) was not detected on admission, but was detected three weeks later. Infection with hepatitis B virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were excluded. The peak titer of anti-HA was higher than would be expected for passive transfer of antibody resulting from transfusions. The persistence of antibody for more than 20 months after the last transfusion was not consistent with passive antibody, which would be expected to disappear over that time. This child had indications for allogeneic marrow transplant and a sibling donor who was histocompatible. However, the transplant was postponed because the prognosis was considered to be poor in the presence of active hepatitis. There was a spontaneous remission without the necessity of the transplantation procedure.
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PMID:Spontaneous resolution of severe aplastic anemia associated with viral hepatitis A in a 6-year-old child. 75 62

Infection is a frequent cause of death in patients receiving bone marrow transplants. Although lymphocyte dysfunction has been observed in a few such patients, no systematic study of neutrophil function has yet been reported. Neutrophil chemotaxis was evaluated by a 51Cr-radioassay after bone marrow transplantation in 34 patients with acute leukemia or aplastic anemia. The response to a chemotactic stimulus (C5a) was severely depressed (less than 35% of normal) in 18 patients, moderately depressed (35-65% of normal) in an additional 6, and normal in 10 subjects. The mean response in the absence of graft vs. host disease and antithymocyte globulin administration was 73.3+/-9.2% (SE) in contrast to 29.7+/-9.6% (P is less than 0.01) in patients with graft vs. host disease treated with antithymocyte golbulin. Both graft vs. host disease and antithymocyte globulin were implicated since the presence of either factor alone was associated with depressed chemotaxis (31.1+/-4.9% for graft vs. host disease, P is less than 0.01; 17.0+/-7.8% for antithymocyte globulin, P is less than 0.02). When normal neutrophils were incubated with antithymocyte globulin in vitro, their chemotactic response was markedly suppressed in the absence of a cytotoxic effect. Transplant patients with defective chemotaxis experienced significantly more infections than those with normal chemotaxis, and analysis of specific etiologic agents showed that this was predominantly related to bacterial pathogens. Chemotactic inhibitors were detected in the sera of seven patients and elevated IgE levels were found in nine subjects, eight of whom had graft vs. host disease. Generation of chemotactic activity by endotoxin activation of serum was reduced in five patients. The results demonstrate a severe defect in neutrophil chemotaxis in some bone marrow transplant patients and suggest that neutrophil dysfunction may predispose to infection in such patients.
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PMID:Defective neutrophil chemotaxis in bone marrow transplant patients. 77 29

Infections due to Ps. aeruginosa are a problem in the tropics as in other parts of the world. Over a four year period, 15 patients attending University College Hospital, Ibadan, were proved to have septicaemia due to this organism and 13 patients died rapidly as a direct result of the infection. The two patients who survived the acute episode had received immediate treatment with at least one antibiotic active against Ps. aeruginosa: a third patient, who received immediate appropriate antibiotic therapy, was already suffering from aplastic anaemia and died rapidly despite treatment. The remaining patients received inappropriate antibiotic therapy because pseudomonas infection was not suspected at the time the diagnosis of septicaemia was made. Patients most at risk appear to be the very young and those with pre-existing malignant or other conditions affecting the defence mechanisms of the body: it is suggested that routine initial management of such patients should include a blood culture, followed by immediate treatment with an antibiotic combination that includes at least one agent likely to be active against Ps. aeruginosa. The development of medical services can lead to the introduction of ophthalmic or other operations on tissues that are highly susceptible to infection before facilities are provided for the maintenance of a pathogen-free environment. Following an outbreak of eye infection after cataract extractions, carried out in an old and unsatisfactory theatre, wide-spread room contamination was demonstrated with the same strains of Ps. aeruginosa that had been responsible for the clinical infections. Chemical disinfection of the theatre floor failed to eliminate the organisms, although other experiments suggested that the drying effect of air-conditioning would be successful in this respect. The wisdom of introducing such operations before the provision of adequate facilities is seriously questioned.
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PMID:Serious infections due to Pseudomonas aeruginosa. 82 57

Infection and acute graft versus host disease (GVHD) are the most common complications of allogeneic bone marrow transplantation, which compromise this therapeutical method for hematologic diseases. Beside the appreciation of customary preventive measures and the treatment of infections, it is necessary for every bone marrow transplantation center to analyze the development of bacterial, fungal and viral infections in the patients and to generate the most efficient and most rational program for their prevention and treatment. At the Hematology Department in Novi Sad seven allogenic bone marrow transplantations were performed in patients with malignant hematologic diseases and severe form of aplastic anemia. Prevention of the infection by isolation of the patient in a sterile unit, selective decontamination of the digestive tract with sterile food, skin and mucus hygiene and prophylactic drug administration proved rather beneficial and adequate for patients with the graft accepted, hematopoiesis recovered and immunity reconstructed. Risks of infections were increased by permanent vein catheter, acute GVHD and rejection of the bone marrow graft. Prompt isolation and identification of bacteria and fungi, especially in blood, the establishment of a minimal suppressing and bactericide antibiotic concentration, along with the assessment of their synergism, as well as early diagnosis of cytomegalovirus and administration of specific drugs, can significantly contribute to the more successful treatment of infections in transplanted patients.
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PMID:[Prophylaxis and therapy of infections in allogenic bone marrow transplantation in patients with hematologic diseases]. 134 65

The patient most susceptible to invasive aspergillosis has had prolonged granulocytopenia resulting from intensive chemotherapy and/or radiation therapy, aplastic anemia, or acute leukemia. The sinuses and lungs are usually involved, but the infection may disseminate to the endocardium, skin, CNS, and eye. Efficacy of antifungal treatment with amphotericin B depends on early recognition and aggressive intervention. In severe or refractory cases, addition of flucytosine, rifampin, or fluconazole may be beneficial. The most ominous presentation of zygomycosis involves sinus and orbital destruction and necrosis. However, pulmonary involvement is the most common manifestation in cancer patients. Infections with Pseudallescheria boydii, Fusarium species, and Trichosporon beigelii are increasingly being recognized in cancer patients, as are Malassezia furfur and invasive mycoses from dematiaceous molds.
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PMID:Approaches to management of fungal infections in cancer patients. 153 71

Patterns of infection were studied in 150 patients with aplastic anemia who were admitted to the Clinical Hematology Branch, National Institutes of Health, between January 1978 and December 1989 for immunosuppressive therapy. Sixty percent of the patients were males, 71% were white, their mean age was 33.6 years (median, 27.5; range, 1-75), and 83% had severe aplastic anemia. One hundred three patients developed 1 or more febrile episodes during the study period. The risk factors for developing a febrile episode included a low Absolute Neutrophil Count (ANC) and Absolute Monocyte Count (AMC) at admission and the presence of an indwelling central venous catheter (Hickman-Broviack or Port-A-Cath). A total of 289 febrile events were studied, including unexplained fever (FUO) in 89 (31%), microbiologically documented infection (MBDI) in 137 (47%), and clinically documented infection (CDI) in 63 patients (22%). Compared to documented infections (MBDI) or CDI), FUO events were associated with a higher frequency of rigors, signs and symptoms of serum sickness, and treatment regimens known to cause fevers. None of the FUO events had a fatal outcome, even if the antibiotic therapy was discontinued before day 7. Among CDI events, bacteria were the most commonly defined etiologic agent (67%), followed by fungi (23%), viruses (7%), and parasites (3%). The patterns of bacterial infections in patients with aplastic anemia were similar to those observed in patients with cancer-related neutropenia. Twenty-one patients (15%) developed invasive fungal infections (aspergillus, 11; candida, 7; and both, 3), which were fatal in 19 (90%). Fungal infections accounted for 30% of the secondary infectious events and for 55% of fatal infectious events. The only identifiable risk factors for developing a fungal infection were the degree of neutropenia and monocytopenia at initial admission or final evaluation. Invasive pulmonary aspergillosis developed despite empirical amphotericin B therapy and was associated with a high incidence of fatal pulmonary hemorrhage (10 of 13 patients [77%]). Infection was responsible for 36 (62%) of the deaths observed during the study period and hemorrhage alone for 4 (7%). However, 20 of the patients who died of infection had concomitant hemorrhage. No significant drop in ANC, AMC, or platelet count could be demonstrated during a fatal infectious event as compared to a nonfatal infectious event. Invasive fungal infections, predominantly with aspergillus and candida, emerged in our study as the major causes of mortality in patients with aplastic anemia. Without bone marrow recovery the prognosis associated with invasive mycoses was grave.
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PMID:Patterns of infection in patients with aplastic anemia and the emergence of Aspergillus as a major cause of death. 154 57

Feline leukemia virus is a naturally occurring, contagiously transmitted and oncogenic immunosuppressive retrovirus of cats. The effects of FeLV are paradoxical, causing cytoproliferative and cytosuppressive disease (eg, lymphoma and myeloproliferative disorders vs immunodeficiency and myelosuppressive disorders). In the first few weeks after virus exposure, interactions between FeLV and hemolymphatic system cells determine whether the virus or the cat will dominate in the host/virus relationship--persistent viremia and progressive infection or self limiting, regressive infection will develop. The outcome of these early host/virus interactions is revealed in the diagnostic assays for FeLV antigenemia and viremia. The latter, in turn, predict the outcome of FeLV infection in cats. Known host resistance factors include age and immune system functional status. Known virus virulence factors are magnitude of exposure and virus genotype. Molecular analysis of FeLV strains indicated that natural virus isolates exist as mixtures of closely related virus genotypes and that minor genetic variations among FeLV strains can impart major differences in pathogenicity. The genetic coding regions responsible for cell targeting and specific disease inducing capacity (eg, thymic lymphoma, acute immunosuppression, or aplastic anemia) have been mapped to the virus surface glycoprotein and/or long terminal repeat regions for several FeLV strains. Infection by specific FeLV strains leads to either malignant transformation or cytopathic deletion of specific lymphocyte and hemopoietic cell population, changes that prefigure the onset of clinical illness. Another notable feature of the biology of FeLV is that many cats are able to effectively contain and terminate viral replication, an important example of host immunologic control of a retrovirus infection and a process that can be selectively enhanced by vaccination. Thus, FeLV infection serves as a natural model of the multifaceted pathogenesis of retroviruses and as a paradigm for immunoprophylaxis against an immunosuppressive leukemogenic retrovirus.
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PMID:Feline leukemia virus infection and diseases. 166 70

Thirty-four patients received bone marrow transplants from unrelated donors. Donors and recipients were phenotypically matched for 6 of 6 HLA-A, B, and DR antigens in 27 cases and at 5 of 6 antigens in 7 cases. Twenty-three patients had leukemia, six had myelodysplasia, and five had aplastic anemia. Twenty-four patients had durable engraftment. Five died of sepsis prior to engraftment. Five patients failed to engraft; 2 of these patients had autologous bone marrow recovery. Seventeen patients developed grade greater than or equal to II acute graft-versus-host disease for an actuarial probability of 67 +/- 20%. The severity of acute graft-versus-host disease and its mortality appeared increased for recipients matched for 5 of 6 HLA-A, B, and DR antigens. Of the 34 patients, 13 (38%) are alive; actuarial survival beyond 6 months is 44 +/- 17%. None of the 25 leukemia and myelodysplasia patients achieving engraftment have relapsed. For leukemia and myelodysplasia recipients of 6 of 6 HLA-matched grafts, actuarial survival at 6 months was 55 +/- 21% compared with 14 +/- 26% for recipients matched for 5 of 6 HLA loci (P = 0.19). Infection and acute graft-versus-host disease were the primary causes of death in the engrafted patients. Survival for aplastic anemia patients was 20%. Late deaths due to pneumonia and bronchiolitis obliterans occurred after one year in 2 patients. Closely matched unrelated donor bone marrow transplants are associated with a higher incidence of graft failure and graft-versus-host disease than typically reported for transplants from HLA-identical siblings, but these preliminary data suggest a lower rate of relapse.
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PMID:Bone marrow transplantation using unrelated donors for patients with advanced leukemia or bone marrow failure. 214 25

Infections are common causes of death in patients undergoing bone marrow transplantation for aplastic anemia or leukemia. A better understanding of the immunologic recovery following marrow grafting may lead to clinical trials of which the goals are to improve immunologic reactivity and to decrease infection.
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PMID:Suppression and recovery of immunologic function after bone marrow transplantation. 308 8


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