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)

Fifteen patients with acute leukemia resistant to standard chemotherapy were treated by bone marrow transplantation from HLA-matched siblings after conditioning with a new combination chemotherapy/radiation therapy regimen--SCARI. SCARI consists of 5 days of high-dose cytosine arabinoside and 6-thioguanine followed by 3 days of daunorubicin. After a rest period, cyclophosphamide and total-body irradiation are given sequentially. This regimen had acceptable morbidity. Median survival was 169 days. Overall survival and disease-free survival was 27% at over 11 months. Relapse rate was 13% of the entire group and 30% by actuarial projection. Relapses were late and initially extramedullary. Deaths from causes other than leukemia occurred early secondary to fungal infection and late secondary to interstitial pneumonia (frequently cytomegalovirus). Graft-versus-host disease and graft rejection were not causes of mortality. In these patients conditioned with SCARI, leukemic recurrences were infrequent but infectious complications were a major hazard.
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PMID:Bone marrow transplantation with intensive combination chemotherapy/radiation therapy (SCARI) in acute leukemia. 1 96

Using the Seattle protocol with minor modifications, 23 patients with severe aplastic anaemia received allogeneic bone marrow transplants from HLA/mixed leucocyte culture matched sibs in three London centres between 1973 and 1977. Ten patients (43.5%) are alive 6 months to 5 years after transplantation, and are well with full haemopoietic reconstitution, two with autologous bone marrow recovery following the graft procedure. A failure of the marrow graft to take, or take followed by rejection occurred in 12 patients (52%). Failure of marrow recovery was associated with a high early mortality from bacterial or fungal infection. The only survivors amongst those who rejected the first graft were four patients in whom a subsequent graft from the same donor was successful, and two in whom autologous recovery occurred. Graft versus host disease (GVHD) occurred in seven patients, and was fatal in one case. The most frequent complication after successful engraftment was varicella-zoster infection which occurred in five patients and was fatal in one patient. The overall results compare favourably with those from other transplant centres, but the high rate of graft rejection and low incidence of GVHD differ from other series. The results should encourage further referral of patients with severe AA for bone marrow transplantation.
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PMID:Allogeneic bone marrow transplantation for severe aplastic anaemia--the London experience. 4 92

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

Multiple benefits of intravenous immunoglobulin (IVIG) therapy after marrow transplantation have been reported, including decreased incidence of acute graft-versus-host disease (GVHD), infection, sepsis, cytomegalovirus (CMV) pneumonitis and platelet use. To test the hypothesis that the observed beneficial effects of IVIG are related to the serum IgG levels achieved, we followed IgG levels (pre-infusion, 1 h and 24 h post-infusion) in 45 consecutive marrow transplant recipients. IVIG 500 mg/kg was given weekly for six doses starting day -8 pre-transplant, then every other week for a total of 11 doses. Forty-one patients (22 allogeneic, 17 autologous, two syngeneic) were evaluable. Patients with acute GVHD had significantly lower serum IgG trough levels (less than 1200 mg/dl) noted at day +20 post-transplant and afterwards than patients without GVHD (greater than or equal to 1200 mg/dl). Pharmacokinetic modeling of the data indicates that IgG half-life between day -8 and day +6 may predict which recipients are at increased risk of acute GVHD. Allogeneic recipients in the group with trough levels less than 1200 mg/dl required more platelet transfusions. Although there was no significant difference in fungal infection rates or bacteremia, sepsis was noted in only two recipients (one allogeneic, one autologous), both with serum IgG trough levels less than 1200 mg/dl. In addition, three allogeneic recipients had cytomegalovirus pneumonitis, all in the group with lower IgG trough levels. Thus, while serum IgG trough levels less than 1200 mg/dl appear to be strongly associated with acute GVHD, low levels may also be associated with increased platelet utilization, with cytomegalovirus pneumonitis, and sepsis, but not with the overall incidence of infection.
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PMID:Some but not all benefits of intravenous immunoglobulin therapy after marrow transplantation appear to correlate with IgG trough levels. 165 38

To evaluate the safety and efficacy of glycosylated recombinant human granulocyte colony-stimulating factor (rhG-CSF) derived from Chinese hamster ovary cells in bone marrow transplantation (BMT), we performed a multi-center phase II clinical study. Sixty-two bone marrow transplanted patients (46 with allograft, 16 with autograft) were enrolled in this study, and rhG-CSF was administered intravenously 30 min daily at a dose of 2, 5, 10, or 20 micrograms/kg/day for 14 consecutive days from day 1 or day 5 after transplantation. Compared with historical control, blood neutrophil recovery in greater than or equal to 5 micrograms/kg/day group was clearly accelerated without delay in other blood cells. Consistent with the acceleration of neutrophil recovery, the number of days with body temperature (greater than or equal to 38 degrees C) decreased during from day 15 to day 28. No adverse effects were observed, and there was no evidence that rhG-CSF affected the incidence of graft-versus-host disease and relapse rates of myeloid leukemia. These results suggest that the posttransplant use of rhG-CSF may be an efficient strategy for reducing the risk of bacterial and/or fungal infection complications in BMT.
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PMID:[Clinical effect of recombinant human granulocyte colony-stimulating factor in bone marrow transplantation. The Japan rhG-CSF Clinical Study Group]. 169 89

The first known case of Blastoschizomyces capitatus meningitis occurring in an allogeneic bone marrow recipient on steroid and cyclosporine therapy for chronic graft-versus-host disease is reported. An 11-month course of treatment with oral fluconazole resulted in resolution of the meningeal syndrome and eradication of Blastoschizomyces capitatus from the cerebrospinal fluid. Three months after discontinuation of fluconazole the patient died due to idiopathic interstitial pneumonia and bilateral pneumothorax, without clinical signs of meningitis. Post mortem examination showed meningeal fungus invasion consistent with Blastoschizomyces capitatus infection. Oral fluconazole treatment thus did not eradicate the fungal infection, but achieved significant control of the meningitis on an outpatient basis.
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PMID:Fluconazole treatment of Blastoschizomyces capitatus meningitis in an allogeneic bone marrow recipient. 181 Jul 30

A phase I dose escalation trial of recombinant human macrophage colony-stimulating factor (rhM-CSF) in combination with conventional antifungal therapy was conducted in 24 marrow transplant recipients with invasive fungal infection. Daily doses ranged from 100 to 2,000 micrograms/m2/d. Toxicity, such as constitutional symptoms, directly ascribed to rhM-CSF was not observed; however, transient, dose-related thrombocytopenia was observed. Patients who received 2,000 micrograms/m2/d of rhM-CSF had a mean reduction in platelet count of 61,000/mm3 during the rhM-CSF infusion period, which was significant when compared with patients who received lower doses of rhM-CSF (P = .008). Fourteen of the 16 patients who received rhM-CSF after undergoing allogeneic bone marrow transplantation had no change in the severity of graft-versus-host disease (GVHD) while receiving rhM-CSF. One had an increase in the severity of GVHD and one had a decrease. There were no effects on neutrophil, monocyte, or lymphocyte counts. Six patients had resolution of their infections, 12 were not evaluable for response, and six did not respond. Ten patients survived 100 days after initiation of rhM-CSF and 14 died. Further trials with rhM-CSF to assess antifungal activity are indicated.
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PMID:Phase I trial of recombinant human macrophage colony-stimulating factor in patients with invasive fungal infections. 186 51

We studied amphotericin B (AMB) serum levels (n = 590) in 41 pediatric patients, who underwent allogeneic (21) or autologous (20) bone marrow transplantation (BMT). All patients received AMB orally as part of a total gut decontamination; 30/41 patients (73%) had AMB i.v. either for prophylaxis or therapy of fungal infections. Rapid initial dose escalation of AMB and the infusion over 1 h only were well tolerated by the children. Serum level monitoring allowed AMB long-term treatment safely to be administered in children suffering from transplantation-related complications (veno-occlusive disease of the liver, graft-versus-host disease of the liver). An h.p.l.c. method was used for monitoring AMB serum trough levels to avoid levels exceeding 2 mg/l. One lethal fungal infection was observed in 41 pediatric BMT recipients (2.4%). Rapidly increasing doses of AMB at start of therapy and drug monitoring by h.p.l.c. might help to reduce fungal mortality and renal toxicity by a dose sparing effect in BMT recipients.
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PMID:Amphotericin B serum levels in pediatric bone marrow transplant recipients. 204 64

Following bone marrow transplantation, patients are profoundly immunodeficient and susceptible to a variety of opportunistic infections. The types of infections vary during different intervals after transplantation. Before engraftment, neutropenia and damaged mucosal surfaces are the predominant deficits in host defenses against infection, and bacterial and fungal infections are the most common infections encountered. During the early post-engraftment period, acute graft-versus-host disease and its treatment result in a severe deficiency of cellular immunity. Cytomegalovirus infection is frequent and can result in life-threatening pneumonia. Fungal infections are also common. After the first three months, infection is much less common. However, reactivation of varicella-zoster virus (VZV) and infections with certain pathogens such as Pneumocystis carinii, can occur due to still-impaired cellular immunity.
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PMID:Management of infectious complications of bone marrow transplantation. 214 70

In a retrospective study of over 1,500 patients who underwent bone marrow transplantation between 1980 and 1987, the incidence of invasive candidal or mold infection was 11% and 4.5%, respectively. Candidemia alone occurred in 46, candidemia and tissue infection in 56, and tissue infection alone in 69 of 1,510 patients analyzed. Aspergillus infection alone occurred in 69, other mold infections occurred in four, and Aspergillus plus other mold infections in two of 1,658 patients analyzed. Median time to onset of candidal infection was 2 weeks and of mold infections 6 weeks after transplantation. Overall mortality for patients with candidal infection was 73% and for those with Aspergillus or other mold infections, 84%. Death occurred in 39% of patients with candidemia alone, 90% of patients with candidal tissue infection with or without candidemia, and 100% of those with mixed infection. The death rate was 75% for patients infected with Aspergillus alone, 83% for those infected with other molds with or without Aspergillus, and 100% when there was coinfection with Candida or cytomegalovirus. The probability of occurrence of Aspergillus infection was influenced by patient age, donor match, type of conditioning regimen, and occurrence of acute graft-versus-host disease (GVHD), while the occurrence of candidal infection was influenced by additional factors including underlying disease and GVHD prophylactic regimen. In contrast to some published reports, the risk of Aspergillus infection was not significantly altered by infection prevention methods, including provision of a protective environment. These data confirm both the high incidence and severity of fungal infection after bone marrow transplantation and underscore the urgent need for more effective prophylaxis and treatment.
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PMID:Fungal infections in bone marrow transplant patients. 235 4


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