Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe our experience of setting up an allogeneic BMT program at the Christian Medical College Hospital, Vellore over a period of 13 years, from October 1986 to December 1999. Two hundred and twenty-one transplants were performed during this period in 214 patients, with seven patients undergoing second transplants. Indication for BMT were thalassemia major - 106 (48%), CML - 30, AML - 35, ALL - 10, SAA - 22, MDS - six and six for other miscellaneous disorders. The mean age of this patient cohort was 15.6 years (range 2-52). Graft-versus-host disease of grades III and IV was seen in 36 patients (17%) and this was the primary cause of death in 20 patients (9.2%). All patients and donors were CMV IgG positive. Sepsis was the primary cause of death in 16 patients (7.4%), 10 bacterial, four fungal and two viral. One hundred and ten of this series of patients are alive and disease free (50%) with a median follow-up of 24 months (range 2-116). These results are comparable to those achieved for patients with similar disease status in transplant units in the Western world and cost a mean of US$15 000.
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PMID:Allogeneic bone marrow transplantation in the developing world: experience from a center in India. 1147 34

All-trans retinoic acid (ATRA) is a known inducer of differentiation in acute promyelocytic leukemia. To improve the outcome of children with acute promyelocytic leukemia, ATRA has been applied since 1994 as an additional induction element inthe AML-BFM 93 study. In a retrospective study, we compared 22 children treated with ATRA (median age: 9.3 years; range: 1.8-16.3) with 22 patients receiving conventional therapy (median age: 12.3 years; range: 3.2-16.7). Twenty-one of the children achieved complete remission. Only one patient died early from bleeding complications after 3 days administration of ATRA. In the control group, seven early deaths occurred (Fisher exact test; p<0.04). Two children died from intracerebral hemorrhages. Two patients suffered from sepsis during aplasia after induction therapy, and one child did not respond to treatment. The 5-year overall survival (OS) and event-free survival (EFS) of the children who received ATRA followed by chemotherapy were significantly bettercom-pared with conventionally treated children [OS: 0.87 +/- 0.9 vs 0.45 +/- 0.11, p (log rank) <0.003; EFS: 0.76 +/- 0.11 vs 0.43 +/- 0.11 p (log rank) <0.02]; the median observation time was 2.8 years (19-76 months). However, nearly all children suffered from common side effects such as headache, fever, joint, muscle and bone pain, weight gain, or dermatitis. In three patients, a retinoic acid syndrome was observed. Interruption of ATRA treatment and application of dexamethasone, necessary in 12 children, controlled theadverse effects. ATRA treatment could be resumed in 18 patients. In conclusion, ATRA treatment during induction could avoid early deaths in children with acute promyelocytic leukemia with considerable but manageable toxic side effects.
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PMID:Treatment with all-trans retinoic acid in acute promyelocytic leukemia reduces early deaths in children. 1152 68

Severe regimen-related toxicity often complicates second transplant procedures performed in patients with hematological malignancies that have relapsed after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melphalan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients received allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative. Diagnoses included AML (n = 9), ALL (n = 1), or Hodgkin's disease (n = 1). Only one patient was in complete remission at the time of second transplant. The median interval between first transplant and relapse was 163 days (range 58-1885). Recipients of HLA-mismatched transplants received antithymocyte globulin in addition to fludarabine and melphalan as part of the conditioning regimen. All 11 patients received acute GVHD prophylaxis consisting of tacrolimus and methotrexate. Ten of 11 patients achieved hematopoietic engraftment with a median time to absolute neutrophil count >0.5 x 10(9)/l and to platelet count of >20 x 10(9)/l of 14 and 19 days, respectively. All engrafting patients achieved 100% donor chimerism on initial analysis, except for one with persistent leukemia at day +19. Two patients experienced grade 3 regimen-related toxicity, manifesting as acute renal failure. Acute GVHD grades 2-4 occurred in two recipients and chronic GVHD in four. The 100-day mortality from all causes was 36%. Ten of 11 patients (91%) died a median of 140 days (range 9-996) after the second transplant. The causes of death included relapse (n = 5), sepsis (n = 4), and idiopathic pneumonia syndrome (n = 1). One patient with AML survives in remission at 880 days post-transplant. We conclude that fludarabine- and melphalan-based conditioning promotes full donor chimerism, even following HLA-mismatched transplants. However, the regimen may be more beneficial when applied to patients undergoing allogeneic HSC transplantation earlier in their disease course.
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PMID:Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant. 1160 68

23 patients with ALL (n=9) and AML (n=14) underwent nonmyeloablative stem cell transplantation (NST) from an HLA-identical donor after conditioning with fludarabine (180 mg/m(2)), busulfan (8 mg/kg) and anti-T-lymphocyte globulin (40 mg/kg). After NST, 20/23 patients engrafted. Ten out of 14 patients with uncontrolled disease reached complete remission. A multiplex-PCR using short tandem repeats was used for chimerism analysis and detected mixed chimerism (MC) in 14/22 evaluable patients (64%) after NST. Prophylactic donor lymphocyte infusions (DLI) were given to 11/14 patients with MC; MC converted to complete donor chimerism (CC) in 6/11 patients within 2-6 weeks. All patients with persistent MC with or without DLI relapsed during further follow-up. MC predicted impending relapse 4-52 weeks before clinical diagnosis. Ten of 23 patients (43%) are alive 2-34 months after stem cell transplantation. 12 of 23 patients (52%), have died from leukaemia after NST. One out of 23 patients has died from severe sepsis. In conclusion, NST leads to stable engraftment and complete remission in patients with advanced acute leukaemias. NST can cure a substantial proportion of these patients, but the relapse rate is still high. Repeated chimerism analysis is a useful tool to detect recipient cells, especially in patients without molecular markers of disease and can be used to monitor immunomodulatory therapies. MC is unstable in these patients and predicts impending relapse. Prophylactic DLI can convert MC to CC, which seemed to lower relapse risk.
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PMID:Reduced intensity conditioning and prophylactic DLI can cure patients with high-risk acute leukaemias if complete donor chimerism can be achieved. 1263 24

Five patients with confirmed Fanconi's anemia (FA) and myelodysplasia and/or leukemia underwent stem cell transplantation (SCT) from related donors at KFSHRC. The median age at SCT was 12.6 year (range, 6.2-15 years). Conditioning regimen consisted of cyclophosphamide (CY) 5 mg/kg/day i.v. for 4 days, total body irradiation (TBI) 450 cGy in a single dose. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine and antithymocyte globulins (ATG). The median time to engraftment (defined as ANC>/=0.5 x 10(9)/l) was 16 days (range, 12-26 days). The median time to a self-sustaining platelet count of >/=20 x 10(9)/l was 27 days (range, 12-40 days). All patients engrafted. Two patients developed acute GVHD; one of the gut (grade 3) and the other of the skin (grade 1), and one patient developed chronic GVHD of the liver. Four are alive and well with no evidence of the disease; one patient died of bacterial sepsis after controlling her GVHD and clearing her pulmonary aspergillosis and CMV infection. We conclude that the use of low-dose CY plus TBI in patients with FA and MDS/AML undergoing SCT is adequate; the regimen is well tolerated and may be curative for such patients.
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PMID:Allogeneic stem cell transplantation in patients with Fanconi's anemia and myelodysplasia or leukemia utilizing low-dose cyclophosphamide and total body irradiation. 1457 32

In addition to the ability of G-CSF to stimulate the maturation and function of granulocytes, experimental and clinical evidence suggests that induction of leukemia cell differentiation may also be possible. This critical effect has received little attention with respect to its potential therapeutic application in myeloid malignancies. We describe the clinical course of a 62-year-old patient with atypical AML1/ETO-positive AML-M2 who repeatedly displayed a marked, dose-dependent response to G-CSF. He was originally investigated for neutropenia, but declined chemotherapy at diagnosis of AML (40% bone marrow blasts) and commenced G-CSF therapy when a life-threatening chest infection occurred. The bone marrow infiltration regressed and his blood counts normalized after 20 days. A slow relapse occurred over the next 3 months but a second hematological remission was achieved upon reintroduction of G-CSF. He remained well and free of transfusions for 2.5 years, receiving only maintenance G-CSF. Despite the presence of the AML1/ETO transcript, his leukemic blasts always failed to demonstrate the typical morphological, immunological and cytogenetic characteristics of AML1/ETO-AML of M2 subtype. He eventually developed resistance to G-CSF and died from sepsis after cytotoxic therapy. In selected AML cases differentiation therapy with growth factors may emerge as a useful antileukemic strategy, either alone or as an adjunct to established treatment modalities.
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PMID:Dose dependent long-term in vivo remission of AML1/ETO positive acute myeloid leukemia with G-CSF. 1520 65

Triapine, an iron chelator and a potent inhibitor of ribonucleotide reductase, has significant anti-leukemia activity. A phase I study of Triapine in combination with ara-C was conducted in 32 patients with refractory acute leukemia and high-risk MDS. Triapine (105 mg/m2/day 6-h infusion) was followed immediately by ara-C [100 (n=4), 200 (n=6), 400 (n=7), or 800 (n=8)mg/m2/day] as an 18-h infusion for 5 consecutive days. Dose-limiting toxicities (DLTs) were observed at the 800 mg/m2 ara-C dose level (one patient each with grade 4 mucositis; grade 4 neutropenic colitis, sepsis; grade 4 neuropathy; and grade 4 hyperbilirubinemia). Therefore, the study was amended to include an ara-C dose level of 600 mg/m2/day, no DLTs occurred in seven patients treated at this dose level. Mean Triapine C(max) and AUC were 1.13 microg/mL and 251.5 minmicrog/mL. Of 31 evaluable patients, 4 (13%) (3 AML, 1 Ph+ALL) achieved a CR (1 at a dose of 800 mg/m2; 2 at 600 mg/m2; 1 at 200mg/m2). The recommended phase II regimen is Triapine 105 mg/m2/day followed by ara-C 600 mg/m2/day for 5 consecutive days every 3-6 weeks.
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PMID:Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. 1647 31

In patients with severe congenital neutropenia (SCN), sepsis mortality is reduced by treatment with granulocyte colony-stimulating factor (G-CSF), but myelodsyplastic syndrome and acute myeloid leukemia (MDS/AML) have been reported. We studied 374 patients with SCN and 29 patients with Shwachman-Diamond syndrome (SDS) on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. In SCN, sepsis mortality was stable at 0.9% per year. The hazard of MDS/AML increased significantly over time, from 2.9% per year after 6 years to 8.0% per year after 12 years on G-CSF. After 10 years, the cumulative incidence was 8% for sepsis mortality and 21% for MDS/AML. A subgroup of SCN patients (29%) received more than the median dose of G-CSF (> or = 8 microg/kg/d), but achieved less than the median absolute neutrophil count (ANC) response (ANC < 2.188 x 10(9)/L [2188/microL] at 6-18 months). In these less-responsive patients, the cumulative incidence of adverse events was highest: after 10 years, 40% developed MDS/AML and 14% died of sepsis, compared with 11% and 4%, respectively, of more responsive patients whose ANC was above the median on doses of G-CSF below the median. Risk of MDS/AML may be similar in SDS and SCN. In less-responsive SCN patients, early hematopoietic stem cell transplantation may be a rational option.
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PMID:The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. 1649 69

Infections with S. aureus with heterogeneous intermediate resistance to vancomycin (hVISA) are occurring more frequently. The detection of these infections, their prevalence, clinical characteristics, and significance are controversial. During 2003 and 2004, all blood culture isolates of methicillin-resistant Staphylococcus aureus (264 patients) at the Sheba Medical Center, Tel Hashomer, Israel, were assessed for hVISA by using the Etest macromethod. A total of 16 patients (6%) were positive for hVISA. Resistance to teicoplanin alone and to vancomycin alone using the Etest macromethod was found in 14 and 10 patients, respectively. Standard MICs to vancomycin were between 1 to 4 mg/ml. Most of these isolates (12 of 16 [75%]) would have been missed without specific testing. The median number of bacteremic days was 4. Seven patients had positive blood cultures for more than 5 days. Twelve patients died, and for eight of these the deaths were directly related to hVISA sepsis. We found that hVISA bacteremia was prevalent in our institution, and we suggest seeking hVISA in patients with persistent S. aureus bacteremia.
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PMID:Prevalence and characteristics of heteroresistant vancomycin-intermediate Staphylococcus aureus bacteremia in a tertiary care center. 1734 63

The objective of this study was to evaluate etiology and consequences of neutropenic fever in AML patients. Two hundred and ninety neutropenic periods following chemotherapy in 84 AML patients were retrospectively evaluated. Neutropenic fever was found in 280 periods (97%). Severe sepsis developed in 35 occasions (13%) and 9 patients (11%) died due to severe sepsis. In 165 episodes with neutropenic fever (59%), the potential causative organism was found in blood cultures. Gram-negative bacteria were more commonly found in patients who developed severe sepsis (40% vs. 23%, p = 0.03). CRP after 2 - 3 days from start with fever was higher in patients with severe sepsis (190 mg/L vs. 96 mg/L, p < 0.001) but the rise in CRP rather coincided than preceded with the development of severe sepsis. Severe sepsis is associated with significant mortality in AML patients. Earlier methods than CRP are needed to predict development of severe sepsis.
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PMID:Neutropenic fever and severe sepsis in adult acute myeloid leukemia (AML) patients receiving intensive chemotherapy: Causes and consequences. 1829 12


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