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

Seven hundred fifty-eight unselected children entered into the United Kingdom Medical Research Council acute lymphoblastic leukaemia UKALL VIII Study and Trial were studied for differences in early treatment-related toxicity according to the type of intramuscular L-asparaginase received. Two hundred seventy-five received a product obtained from Escherichia coli and 483 the enzyme from Erwinia chrysanthemi. The E. coli patients had a significantly higher incidence of neurotoxicity, pancreatitis, and life-threatening sepsis (4%, 2%, and 20%, respectively) when compared with the Erwinia group (2%, 0%, and 18%). Severe hypersensitivity was seen in one patient from both groups and the incidence of glucose intolerance was not significantly different. These findings indicate that E. coli asparaginase may be more toxic. With a minimum follow up of 4 1/2 years there is no evidence that either product has made a significantly different contribution to disease-free survival.
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PMID:Non-randomised study comparing toxicity of Escherichia coli and Erwinia asparaginase in children with leukaemia. 223 23

A 46-year-old woman was admitted to our hospital because of leukocytosis. A diagnosis of acute lymphoblastic leukemia (FAB: L2 type) was made by reviewing peripheral blood smear and bone marrow aspirate. Chromosome analysis showed the presence of Philadelphia chromosome. A combination chemotherapy with L-asparaginase, doxorubicin, vincristine, and prednisolone was started, but complete remission was not achieved. During a neutropenic period after combination chemotherapy with doxorubicin, vincristine, vinblastine, and VP-16, high fever and tender swelling of the right cheek were noticed. A diagnosis of maxillary sinusitis was made with tomography and CT scan of the maxillary sinus. Since culture of the aspirate from the maxillary sinus grew aspergillus, a diagnosis of aspergillosis of the maxillary sinus was made. Immediately after the intravenous administration of amphotericin B and the lavage of the sinus with amphotericin B was started, high fever subsided and clinical improvement was observed. Several regimens of chemotherapy failed to obtain hematological remission, she died of sepsis of Enterobactor cloacae without evidence or relapse of dissemination of aspergillosis after initial successful treatment. While a few cases with aspergillus maxillary sinusitis were reported in leukemic patients, the possible occurrence of this complication must be kept in mind in a severe neutropenic period after intensive chemotherapy. The combination of intravenous administration and local lavage of amphotericin B appeared to be an effective treatment in the Aspergillus maxillary sinusitis.
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PMID:[Aspergillosis of the maxillary sinus in a patient with Ph1 positive acute lymphoblastic leukemia: a case report]. 224 25

A polyethylene glycol conjugate of L-asparaginase (PEGLA) was administered to 21 patients with refractory non-Hodgkin's lymphoma. The dose given was 2,000 mu/m2 intramuscularly every 2 weeks. Eligibility required at least one prior trial of chemotherapy and ambulatory performance status. At entry, all patients had measurable lesions and documented disease progression. The median age of the patients was 61 years; 18 (86%) were ambulatory with minimal symptoms, 12 patients (57%) had 3 or more prior regimens, and 13 (62%) had stage IV disease. Histologic subtype was low grade in 11 patients (52%), intermediate in 7 (33%), high grade in 2 (10%) and unclassifiable in one (5%). There were two partial responses (11%) noted (95% confidence interval of response of 1-30%). Eleven patients (52%) were removed from study due to disease progression. Nine patients (43%), required removal for toxicity (7 for protracted nausea and vomiting and 2 for confusion). One patient died of sepsis while on study but this was not considered drug related. Almost one third of patients complained of fatigue or loss of appetite. Nausea and vomiting occurred in approximately half the patients and was moderate to severe in 9. Diarrhea and abdominal pain were also noted in one-third of those treated. Changes in the partial thromboplastin time and fibrinogen were noted in most patients but resulted in no bleeding complications. In this trial, PEGLA displayed modest activity in a heterogenous group of patients with progressive non-Hodgkin's lymphoma.
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PMID:A phase II trial of PEG-L-asparaginase in the treatment of non-Hodgkins lymphoma. 234 67

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 activity of complement-mediated opsonin was measured by the whole blood chemiluminescence method in 17 children with hematologic malignancy (including 6 with ALL, 7 with ANLL and 4 with non-Hodgkin's lymphoma) during remission induction therapy. The activity of opsonin, which was at the normal level before chemotherapy, decreased in all of the children during the therapy. This phenomenon was especially marked in the children treated with L-asparaginase. Although no clear relationship was found between the decrease in opsonin activity and the susceptibility to infection, it was confirmed that in 4 children having an episode of sepsis or septic fever, the infection started when the granulocyte decreased to the nadir, and simultaneously the activity of opsonin decreased. Therefore, it may be reasonable to suspect the decrease in opsonin activity when treating children with such infections.
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PMID:Impairment of opsonic function in children with hematologic malignancy during remission induction therapy. 399 81

Analysis of the remission induction phase in three Medical Research Council trials of treatment of acute lymphoblastic leukaemia has provided evidence of the adverse effect of the combination of colaspase (L-asparaginase) with vincristine and prednisolone. Significant myelosuppression, particularly of the granulocytic series, resulted in an increase in Gram-negative sepsis and death during the neutropenic phase induced by colaspase. The rate of blast-cell regression was increased by colaspase. It is suggested that the introduction of colaspase should be delayed until there is evidence of bone marrow regeneration in order to procure this benefit without the attendant toxicity.
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PMID:Myelosuppressive effect of colaspase (L-asparaginase) in initial treatment of acute lymphoblastic leukaemia. 460 4

Twelve dogs with lymphosarcoma and hypercalcemia were treated over a period of 36 months. Signs and laboratory findings were referable to hypercalcemia and azotemia. All dogs were staged, classified histologically, and given cytoreductive chemotherapy, using 5 drugs (vincristine sulfate, cytosine arabinoside, cyclophosphamide, L-asparaginase and prednisone). For azotemia, symptomatic therapy (0.9% NaCl solution and furosemide) was given. Seven dogs responded completely, with marked reduction of lymphadenopathy and return of serum calcium concentration to normal. Median duration of remission in this group was 48 days (range, 14 to 93), and median survival time was 112 days (range, 85 to 153). Five nonresponding dogs had less than 50% reduction in measurable tumor mass, although serum calcium concentration returned to normal. The median survival time for this group was 34 days (range, 23 to 68). Two of the nonresponders died from sepsis and another from disseminated intravascular coagulation. Response to therapy did not appear to be influenced by age, breed, sex, initial calcium concentration, degree of azotemia, or histologic classification.
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PMID:Chemotherapeutic responses in dogs with lymphosarcoma and hypercalcemia. 689 39

A nine-year old girl with T cell acute lymphoblastic leukemia (ALL) had acute severe neurologic complications at the end of the remission-induction chemotherapy course. Thirty-six hours following triple intrathecal (IT) therapy and intravenous (IV) administration of L-asparaginase (L-asp), tetraplegia developed and she became unconscious. She had bouts of hypertension and persistent tachycardia unresponsive to digitalis therapy. Magnetic resonance imaging (MRI) showed multiple brain white matter hyperintensities and filling defects in the saggital sinus, suggesting thrombosis. Over the 40 days, in addition to her neurologic compromise she also had transient diabetes mellitus, severe hyperlipidemia, hypoproteinemia and edema, liver and heart failure and staphylococcus aureus sepsis with prolonged bone marrow depression. Despite, coexistence of all these chemotherapy related complications, her neurologic functions and multiple organ failure improved gradually. After a 70 days' period of interruption, chemotherapy was resumed and continued without any further complications. Although, the etiology of her extensive sensitivity to some drugs remains unclear, we believe that it is important to document these unusual events in this child.
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PMID:Coexistence of life threatening chemotherapy related leukoencephalopathy, saggital sinus thrombosis and multiple organ failure in a child with acute lymphoblastic leukemia: an unusual case with clinical recovery. 932 1

Diabetic ketoacidosis (DKA) and pancreatic pseudocysts are rare complications following treatment of hematological malignancies with L-asparaginase (L-asp). Persistent hyperglycemia with recurrent DKA presenting as a long-term complication of L-asp-induced pancreatitis is even rarer. A 21-year-old man with pre-B-type acute lymphoblastic leukemia (ALL) developed pancreatic pseudocysts, DKA and persistent hyperglycemia after L-asp therapy. The patient was treated with oral hypoglycemic agents (OHA) for sugar control thereafter. Ten months later, another episode of DKA developed during relapsed ALL without having obvious precipitating factors. Insulin was then instituted for control of his blood sugar until death. The leukemic process may play some role in glucose homeostasis and may be considered as a precipitating factor for DKA. The patient finally died of disease progression of ALL and sepsis 2 years after the initial diagnosis of ALL.
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PMID:Diabetic ketoacidosis and persistent hyperglycemia as long-term complications of L-asparaginase-induced pancreatitis. 1243 31


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