Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We administered recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) (120 micrograms/m2/d by continuous intravenous [IV] infusion) to 12 patients with newly diagnosed acute myeloid leukemia (AML) at relatively high risk of early death during remission induction. GM-CSF began 3 days after completion of induction chemotherapy (ara-C 1.5 g/m2 d x 4 days by continuous IV infusion after a 3 g/m2 bolus). Rates of fatal infection (42%), pneumonia and/or sepsis (83%), and CR (50%) did not differ significantly (P less than .05) from those observed after administration of the identical chemotherapy without GM-CSF to 53 historical controls with newly diagnosed AML at similarly high risk of early death. There were no significant differences between the GM-CSF-treated and the historical groups in the time required to reach neutrophil counts of 500 or 1,000/microL after administration of chemotherapy. Four patients died of infection before they could have benefited from the earliest recovery of neutrophil count observed in patients who entered CR. Growth of leukemia after GM-CSF administration was observed in only 1 of the 8 patients who survived long enough for response to induction therapy to be fully evaluated. This observation suggests that it might be safe to undertake larger, randomized studies, perhaps using earlier administration of GM-CSF, to definitively determine the role of GM-CSF added to chemotherapy in patients with newly diagnosed AML.
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PMID:Treatment of poor-prognosis, newly diagnosed acute myeloid leukemia with ara-C and recombinant human granulocyte-macrophage colony-stimulating factor. 218 1

Based on in vitro evidence of time-dependent synergistic kill of HL-60 leukemia cells exposed to Ara-C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21-75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara-C plus daunorubicin. Each dose of Ara-C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44-68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progressive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug-induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate-dose Ara-C and mitoxantrone is an active and well-tolerated antileukemic regimen.
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PMID:Sequential intermediate-dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia. 220 4

The application of autologous bone marrow transplantation (ABMT) in treating acute leukemias in children has been limited by the presence of residual occult viable leukemic cells in the marrow cell suspension. One approach to this problem is the ex vivo treatment ("purging") of the autograft to eradicate these tumor cells yet spare the normal lymphohematopoietic stem cells. Initial studies of acute myeloid leukemia (AML) in a rodent model demonstrated that incubation with 4-hydroperoxycyclophosphamide (4HC), a congener of cyclophosphamide and an active alkylating agent in aqueous solution, could effectively eliminate viable AML cells from marrow cell suspensions without apparent toxicity to normal stem cells. We have conducted clinical trials of ABMT with 4HC-treated marrow in children with acute leukemia in remission; marrow was collected, treated ex vivo with 4HC (100 micrograms/ml), and cryopreserved in liquid nitrogen until reinfusion. Children received pre-ABMT conditioning with either high-dose cyclophosphamide and total body irradiation (CY-TBI) for acute lymphocytic leukemia (ALL) or high-dose busulfan and cyclophosphamide (BU-CY) for AML. Of nine children who underwent ABMT with 4HC-treated marrow for ALL in second complete remission (CR2), all relapsed (eight in the marrow, one in the central nervous system) at a median of 5 months (range, 2-17) after ABMT and all have died with relapsed ALL or as a consequence of its treatment. Twenty-nine children with AML (five in CR1, 24 in CR2) received autografts with chemopurged marrow at a median remission duration of 3 months (range, 2-15). Three patients died from sepsis during aplasia; 10 children (one in CR1 and nine in CR2) relapsed with AML at a median of 7 months (range, 2-23) after ABMT, for an actuarial relapse rate of 47%. Sixteen patients with AML (four in CR1, 12 in CR2) are in unmaintained remission at a median of 16 months (range, 6-102) after ABMT, for an actuarial disease-free survival of 49%. Although ABMT with 4HC-treated marrow appears to have a limited role in the treatment of children with ALL who lack a suitable related donor, the results in AML are encouraging and compare favorably with both syngeneic and allogeneic BMT in similar groups of patients.
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PMID:Ex vivo chemopurging of autologous bone marrow with 4-hydroperoxycyclophosphamide to eliminate occult leukemic cells. Laboratory and clinical observations. 224 Apr 70

We previously administered ara-C at a dose rate of 250 mg/m2/hr for 36-72 hr to patients with leukemia. Gastrointestinal toxicity was dose-limiting. This regimen was modified to an every other day schedule, administering 24-hr periods of high dose continuous infusion ara-C, each followed by a 24-hr rest period. Sixteen patients with relapsed/refractory acute myeloid leukemia (AML) (N = 4), secondary AML (N = 2), relapsed/refractory acute lymphoblastic leukemia (N = 7), or CML in blast crisis (N = 3) received this regimen of three 24-hr infusions with two intercurrent 24-hr rest periods. Grade 3 gastrointestinal toxicity was encountered in 57% of the courses, and hypoplasia was achieved in all patients. Three of the patients died while hypoplastic, two with septicemia and another with intracranial hemorrhage. There were five responding patients (2 CRs, 3 PRs). Median steady-state plasma ara-C levels were 24 microM, 22 microM, and 20 microM during the first, second, and third 24-hr infusions, respectively. Ara-C levels ranged from 4-118 microM during the infusions and were always below 4.5 microM during the rest periods. A significant level of ara-C incorporation into DNA was detected in each of the five patients studied, thus demonstrating that (ara-C)DNA formation is detectable in blasts from patients receiving high dose continuous infusion ara-C therapy. These findings suggest that alternate day continuous infusion ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.
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PMID:A phase I study of intermittent continuous infusion high dose cytosine arabinoside for acute leukemia. 224 7

A case of disseminated infection with Trichosporon capitatum is reported in a 23-year-old patient with acute myeloid leukemia undergoing HLA-mismatched bone marrow transplantation. He was receiving immunosuppressive therapy with cyclosporine and corticosteroids for acute graft-versus-host disease and he was severely neutropenic. While being treated with fluconazole for 28 days for an oropharyngeal candidiasis the patient developed a T. capitatum septicemia. He died despite receiving amphotericin B therapy. Autopsy revealed widespread infection with T. capitatum. The portal of entry was probably the digestive tract in this patient as T. capitatum had been first isolated in the stools.
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PMID:Disseminated Trichosporon capitatum infection in a patient with acute leukemia undergoing bone marrow transplantation. 225 63

The efficacy and safety of a combination regimen using cefmetazole (CMZ) and netilmicin (NTL) were evaluated in the treatment of infections complicated with hematological disorders. Primary diseases in 31 patients included in the evaluation were acute myelocytic leukemia (3 cases), acute lymphocytic leukemia (2 cases), malignant lymphoma (14 cases), chronic myelocytic leukemia (2 cases), chronic myelocytic leukemia blast crisis (4 cases), myelodysplastic syndrome (2 cases), aplastic anemia (3 cases), and malignant histiocytosis (1 case). Complicated infections included 29 cases of suspected septicemia, 1 case of septicemia and 1 case of pneumonia. Clinical responses were excellent in 6 (19.4%), good in 12 (38.7%), fair in 1 (3.2%) and poor in 12 (38.7%). The total clinical efficacy rate was 58.1%. No significant effect of initial neutrophil counts was observed on response rates. Patients who showed increasing neutrophil counts during therapy had higher response rates than those in whom the neutrophil count decreased or remained unchanged at levels less than 500/mm3 in after neutrophil counts. No side effects were observed in any of the 31 patients. In conclusion, this combination therapy of CMZ and NTL thus appears to be useful and safe in therapies for infections complicated with hematological disorders.
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PMID:[Therapeutic effects of a combination treatment with cefmetazole and netilmicin against infections complicated with hematological disorders]. 228 53

Since 1984, 47 patients with untreated acute myeloid leukemia (AML) were hospitalized in a special hematology unit for aggressive chemotherapy. Complete remission was obtained in 68%, 15% died of complications of treatment (infections and bleeding) and 15% had refractory leukemia. The actuarial survival after 3 years for patients in remission was 43%. No patients with refractory leukemia lived more than 1 year. The actuarial remission at 3 years of 21 patients who received additional courses of aggressive chemotherapy (consolidation treatment) was 42%, as opposed to 11% in 11 patients who received maintenance treatment. The 47 patients received 108 courses of aggressive chemotherapy including 47 for induction of remission. During 86 courses (80%) the patients developed fever and in 33 blood cultures were positive; during 16 courses a fungal infection developed. The most common bacterial infection was by E. coli. During the first induction treatment 5 patients died of sepsis and 1 of cerebral hemorrhage. None died during consolidation therapy. During the year preceding the opening of the unit, 12 AML patients were treated on regular medical wards, and five (42%) achieved a complete remission, while 6 died of complications during the first course of induction chemotherapy. Our findings are in line with those of similar units, which indicates the importance of special nursing units for the treatment of acute leukemia.
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PMID:[Treatment of acute myeloid leukemia in a special hematology unit]. 231 3

Autologous bone marrow transplantation, using unpurged cryopreserved autologous marrow, was performed on ten adult patients with acute myeloid leukaemia in remission. Seven patients were in first chemotherapy-induced remission of their disease, while three were in later remission. Patients ages ranged from 24 to 52 years, with a median of 38.5 years. Conditioning therapy consisted of oral busulphan 16 mg/kg over four days and intravenous cyclophosphamide 60 mg/kg on two days. Bone marrow cells were thawed and infused two days later. All patients showed signs of marrow engraftment, however this was delayed in comparison with patients receiving allogeneic transplants. All patients developed fever requiring antibiotic therapy and one patient died of overwhelming sepsis. Another patient died of hepatic veno-occlusive disease two months after transplant. Serious, but non-fatal, hepatic complications occurred in two other patients. One patient, transplanted in third remission, relapsed 16 months post-autograft. No other relapses have been seen, with one second remission patient remaining leukaemia-free at 24 months, and six first remission patients in continuing remission 11 to 23 (median 20) months post transplant. These encouraging results require confirmation in a randomised clinical trial comparing autologous marrow transplantation versus standard chemotherapy.
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PMID:Autologous bone marrow transplantation for acute myeloid leukaemia in remission: a preliminary report. 232 97

Twenty-one acute myelogenous leukemia (AML) patients were submitted in second remission (II CR) to BAVC conditioning regimen followed by unpurged ABMT. Transplant was done after a median of 2 months from II CR (range, 1 to 13). Median first remission (I CR) duration was 16 months (range, 1-35). Conditioning regimen was well tolerated, with no major extra-medullary toxicity. One patient died during aplasia from fungal sepsis. Of the 20 evaluable patients, nine relapsed after a median time of 6 months (range, 2 to 18). Eleven patients are in continuous complete remission (CCR) after a median follow-up of 40 months (range, 24 to 63). The duration of II CR has exceeded the duration of I CR in all patients in CCR. Projected probability of disease-free survival is 52% at 63 months.
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PMID:BAVC regimen and autologous bone marrow transplantation in patients with acute myelogenous leukemia in second remission. 235 May 75

A 73-year-old male was admitted to our hospital in October 1987 because of severe anemia, anorexia, and loss of weight. The hemoglobin level was 5.7 g/dl, the white blood cell count 2,500/microliters with 5% myeloblasts positive for peroxidase, and the platelet count 8.6 x 10(4)/microliters. The LDH was 656 mU/ml, the total protein in the serum 7.4 g/dl, IgG 419 mg/dl, IgA 104 mg/dl, IgM 10 mg/dl, and urine Bence Jones (BJ) protein 8.8 g/day. The X-ray survey of the bones showed multiple osteolytic lesions. A bone marrow aspirate was hypercellular with 91.4% plasma cells, and was cultured a whole day for chromosome study. It revealed an abnormal karyotype of 46, XY, -15, t(6; 14) (p21.1; q32.3), +der(15)t(1; 15) (q23; q24). Immunoelectrophoresis demonstrated lambda type BJ protein. He was treated with melphalan and prednisolone. Proteinuria and marrow plasma cells decreased in amount. In December a white cell count was 6,030/microliters with 80% myeloblasts. A bone marrow aspirate revealed an increase of 82.6% myeloblasts or promyelocytes. The patient was refractory to chemotherapy and died of sepsis in April 1988. An unrelated abnormal karyotype; 48, XY, +8, +13 appeared concomitant with an increase of the leukemic cells, but no cells showed the t(6; 14). We cytogenetically discussed the simultaneous presence of multiple myeloma with acute myelogenous leukemia.
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PMID:[Acute myelogenous leukemia (M2) simultaneously associated with multiple myeloma with special reference to chromosome abnormality of t(6; 14) (p21.1; q32.3)]. 236 41


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