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)

An escalating-dose trial of idarubicin, used weekly for 3 doses in combination with vincristine, prednisone, and L-asparaginase (VPLI), to reinduce remission of childhood ALL at first bone marrow relapse was conducted by the Childrens Cancer Study Group (CCSG). The maximum tolerated dose (MTD) of idarubicin, used in the manner, was determined to be 12.5 mg/m2/dose. Twelve of 16 (75%) evaluable patients in first marrow relapse of ALL treated at a dose of 10 or 12.5 mg/m2 entered a second complete remission, compared to 41 of 69 evaluable patients (59%) treated in a comparable way with daunorubicin (30 mg/m2) (VPLD). Prolonged myelosuppression was observed in both groups, but the frequency of documented bacterial sepsis and the duration of required hospitalization were greater among patients treated with idarubicin. No additional toxicity, specifically attributable to idarubicin, was observed at these doses.
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PMID:Determination of the maximum tolerated dose of idarubicin when used in a combination chemotherapy program of reinduction of childhood ALL at first marrow relapse and a preliminary assessment of toxicity compared to that of daunorubicin: a report from the Childrens Cancer Study Group. 173 17

A national childhood acute lymphoblastic leukemia (ALL) study was initiated in Israel in 1984 with the aim of improving results in difficult aspects of treatment including: high-risk groups, the problems of late relapses, and the effect of cranial irradiation for CNS prophylaxis in leading to late neuropsychiatric sequelae and secondary tumors. Induction of chemotherapy with a combination of 6 drugs (vincristine, cyclophosphamide, cytosine arabinoside, adriamycin, prednisone and L-asparaginase), followed by intensification with methotrexate and L-asparaginase, was introduced in both the usual and the high-risk groups. In a selected group with better prognostic factors, therapy was reduced. In an attempt to minimize the sequelae of CNS prophylactic therapy, cranial irradiation was omitted in half the patients and intrathecal (IT) triple therapy was given instead. Following 2 years of unsatisfactory preliminary results in a very high-risk group (VHR; non-T- and T-cell leukemia with WBC counts of greater than 100,000 and greater than 20,000, respectively), treatment was modified and intensified. Between Nov. 1984 and Feb. 1989, 143 patients were enrolled from 10 hospitals. During follow-up of a median of 2.5 years, there were 32 failures (2 failed remissions, 27 relapsed and 3 died of bleeding and sepsis). 107 patients are alive in first remission and an additional 8 in second and third remissions. By Kaplan-Meier life table analysis, the rates of leukemia-free interval (LFI) and event-free interval (EFI) for 4 years were 60% and 57%, respectively. Improved LFI results of 71% for 4 years were achieved in a group with non-T-cell ALL with WBC less than 100,000 (the largest group, 65% of the patients). In the small "good risk" group (10% of patients), and the T-cell group with WBC less than 100,000, LFI for 4 years were 56% and 54%, respectively. In the VHR group, modification seemed to have improved results: LFI of 41% for 3 years. CNS prophylaxis with IT triple therapy was as effective as cranial irradiation in the standard risk group. In 1 out of 33 children on this protocol a single CNS relapse occurred, as compared to 2 out of 35 matched controls with cranial irradiation. These results warrant extension of IT triple therapy to higher risk groups of childhood ALL. As for systemic treatment, increased up-front high-dose intensive therapy is recommended for all groups with ALL, but with reduction of cumulative dose to minimize late effects.
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PMID:[Israel national childhood acute lymphoblastic leukemia study]. 235 44

The presence of early-onset sepsis significantly affects the prognosis of childhood acute lymphoblastic leukemia (ALL). We retrospectively analyzed all the septic episodes that occurred within 30 days of diagnosis of ALL from January 1978 to June 1994. Within the study period, 51 early septic episodes occurred in 45 patients. This accounted for 36.2% of the total number of septic episodes (141) that occurred during this period. The rate of early-onset sepsis in childhood ALL was 11.3% (45/397). The patients ages ranged from 11 months to 14.7 years. Fortyeight episodes of sepsis were caused by single organisms and three were polymicrobic. Pseudomanas aeruginosa was the most common isolate, followed closely by Staphylococcus aureus, Escherichia coli, Streptococcus spp and Salmonella spp. The case fatality rate of early-onset sepsis was 35.6% (16/45). The average time between diagnosis and death was 5.2 days (median, 1 d). Sepsis caused by P. aeruginosa had the highest mortality, with a case fatality rate of 72.7% (8/11), followed by polymicrobial infections (66.7%, 2/3) and candidemia (66.7%, 2/3). In the adolescent age group, initial white blood cell count < 2.0 x 10(9)/L, and depressed immunoglobulin level (especially IgA) were risk factors for a fatal outcome. During the study period, which covered 16.5 years, the incidence of Gram-positive cocci, especially Streptococcus spp, increased significantly and the overall outcome associated with early-onset sepsis improved.
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PMID:Early-onset sepsis in children with acute lymphoblastic leukemia. 896 71

The relapse rate in childhood acute lymphoblastic leukemia (ALL) is approximately 30% but few reinduction regimens have investigated the intensive use of polyethylene glycol Escherichia coli asparaginase (PEG-Asp). Therefore, we assessed the pharmocokinetics and efficacy of PEG-Asp in this setting. Children with B-precursor ALL, in first marrow and/or extramedullary relapse were eligible. Reinduction included doxorubicin on day 1, prednisone for 28 days, vincristine weekly for 4 weeks, and PEG-Asp either weekly or biweekly by randomization. Asparaginase levels and antibody to both E coli asparaginase and PEG-asp were measured weekly just before each PEG-asp dose. Overall, 129 of 144 patients (pts) (90%) achieved a complete remission (CR). There was a highly significant difference in CR rates between weekly (69 of 71; 97%) and biweekly (60 of 73; 82%) PEG-Asp dosing (P =.003). Grade 3 or 4 infectious toxicity was common (50%), but only 4 pts died of sepsis during induction. Other toxicities were infrequent and hypersensitivity was rare (6 of 144; 4%). Low asparaginase levels were associated with high antibody titers to either native (P =.024) or PEG asp (P =.0013). The CR rate was significantly associated with higher levels of asparaginase (P =. 012). Patients with ALL in first relapse receiving weekly PEG-Asp had a higher rate of second remission compared with biweekly dosing. Low levels of asparaginase were associated with high antibody titers. Increased asparaginase levels may correlate with an improved CR rate. The use of intensive PEG-Asp should be explored further in the treatment of ALL. (Blood. 2000;96:1709-1715)
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PMID:Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a Pediatric Oncology Group Study. 1096 68

The severe endothelial dysfunction in children with acute lymphoblastic leukemia (ALL) can result from the disease itself, from treatment, or from other conditions (e.g. sepsis). The aim of this study was to determine the levels of markers of endothelial activation in children with ALL and to assess their potential prognostic value. Fifty-two children with ALL, 19 children with ALL 1-10 years after the completion of therapy, and 28 healthy children were studied. In children with ALL, there was a significant increase in thrombomodulin (TM) and von Willebrand factor (vWF) levels during the acute phase of the disease and during treatment. Children with an unfavorable outcome had higher levels of TM. In conclusion, severe endothelial dysfunction is present during the acute phase of ALL and during treatment and appears to result from the disease itself. Serum TM and vWF levels might represent additional, but not independent, prognostic markers in childhood ALL.
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PMID:Thrombomodulin and von Willebrand factor: relation to endothelial dysfunction and disease outcome in children with acute lymphoblastic leukemia. 2115 Jan 80

This systematic review and meta-analysis compared the efficacy and toxicity of dexamethasone (DEX) versus prednisone (PRED) for induction therapy in childhood acute lymphoblastic leukemia (ALL). We searched biomedical literature databases and conference proceedings for randomized controlled trials comparing DEX and PRED during induction therapy for childhood ALL. A total of eight studies were eligible for inclusion in this meta-analysis. DEX, in comparison with PRED, reduced events (that is, death from any cause, refractory or relapsed leukemia, or second malignancy; risk ratio (RR) 0.80; 95% confidence interval (CI), 0.68-0.94) and central nervous system relapse (RR 0.53; 95% CI, 0.44-0.65), but did not alter bone marrow relapse (RR 0.90; 95% CI, 0.69-1.18) or overall mortality (RR 0.91; 95% CI, 0.76-1.09). Patients receiving DEX had a higher risk of mortality during induction (RR 2.31; 95% CI, 1.46-3.66), neuro-psychiatric adverse events (RR 4.55; 95% CI, 2.45-8.46) and myopathy (RR 7.05; 95% CI, 3.00-16.58). There was no statistically significant difference in the risk of osteonecrosis, sepsis, fungal infection, diabetes or pancreatitis. DEX in induction therapy for children with ALL is more efficacious than PRED. However, DEX is also associated with more toxicity, and currently it remains unclear whether short-term superiority of DEX will also result in better overall survival.
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PMID:Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis. 2152 34

In childhood acute lymphoblastic leukemia, high treatment-related mortality, especially in the induction phase of treatment, is a major challenge for developing countries. The reasons are multifactorial, including a late presentation with higher disease burden, malnourishment, and limited support services. These factors may aggravate the toxic effects of upfront multiagent chemotherapy in terms of severe neutropenic sepsis and tumor lysis. Therefore, instead of upfront chemotherapy, we offered prednisolone prophase for 1 week with the objective of balancing the antileukemic versus the toxic effect of treatment. The data of 538 patients who received induction with this approach (cohort B) are compared for induction mortality with previous records of 438 patients (cohort A) treated with upfront chemotherapy. In the presence of similar clinical characteristics including age, sex, risk group, and phenotype in both cohorts, a significant difference was found in overall induction mortality of 9% in cohort B versus 14% in cohort A (P<0.05). This difference was also significant in the high-risk and T-cell phenotype, which strengthens our hypothesis that patients with higher burden of disease may experience more fatal toxic effects with upfront intensive chemotherapy. Therefore, we suggest that the prednisolone prophase approach is beneficial to control the disease with less severe toxic effects in our settings.
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PMID:Prednisolone Prophase for a Week Versus Upfront Multiagent Chemotherapy in Childhood Acute Lymphoblastic Leukemia: An Analysis With Reference to Induction Mortality in a Developing Country. 3168 27