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)

Soluble receptors have been identified for most members of the TNF-receptor/NGF receptor superfamily. CD95 (Fas/Apo-1) is of particular importance, since its triggering may induce apoptosis in sensitive cells. Recently, a soluble form of the CD95 molecule was described which interacts with the CD95-CD95 ligand death pathway. Increased concentrations of soluble CD95 (sCD95) were previously detected in some patients with T and B cell leukemias and lymphomas. In the present study we investigated sCD95 in the serum of patients with myeloid leukemias, myeloproliferative and myelodysplastic syndromes. A total of 72 patients was studied (29 AML, 17 MDS, 20 CML and six other myeloproliferative disorders). In AML with active disease, the levels of sCD95 tended to be elevated, but did not correlate with defined clinical or laboratory parameters. In the other disorders, the levels of sCD95 were not generally increased, although some patients had elevated levels. These data strongly suggest that sCD95 in AML patients is not derived from leukemic cells, but is possibly secreted or shed from reactive or stromal cells. This hypothesis is also supported by a group of eight patients with septicemia but not leukemia who had elevated sCD95 (P < 0.05). Furthermore, all three patients with elevated sCD95 who had undergone chemotherapy for AML had major infections. Taken together, this study shows that measuring soluble Fas-receptor in myeloid leukemia is not diagnostically useful, but increased sCD95 may be associated with clinical complications like septicemias.
Leukemia 1996 Sep
PMID:Soluble FAS (CD95) is not elevated in the serum of patients with myeloid leukemias, myeloproliferative and myelodysplastic syndromes. 875 76

The study was designed to determine whether administration of granulocyte colony-stimulating factor (G-CSF) following fludarabine would reduce the incidences of myelosuppression and infections. Twenty-five previously treated patients with Rai stage III-IV chronic lymphocytic leukemia (CLL) received fludarabine 30 mg/m2 daily for 5 days each month. G-CSF was given at 5 microg/kg subcutaneously starting 1 day after chemotherapy (day 6) and continued until the next course unless the granulocyte count was > or =10000/microl. The incidences of myelosuppression and infection were compared with those seen in an historical control population of 145 previously treated patients with Rai stage III-IV CLL who were given the same schedule of fludarabine without growth factor. There was a significant decrease in myelosuppression; patients receiving G-CSF developed neutropenia at a neutrophil count <1000/microl or 500/microl in 45% and 15% of courses vs 79% (P=0.002) and 63% (P < 0.001) of historical controls. Twenty percent of G-CSF-treated patients had therapy delayed by >35 days per course, vs 50% of historical controls (P=0.005). The incidence of pneumonia was 8% with G-CSF and 37% without in historical controls. Other infection rates (sepsis, fever of undetermined origin, minor infections) were similar. This decrease in pneumonia was noted even in high-risk groups such as patients older than 60 years and patients with hypogammaglobulinemia. The use of G-CSF following fludarabine in high-risk patients with CLL resulted in a significant decrease in myelosuppression and pneumonia. Larger trials to verify these results and to compare costs are indicated.
Leukemia 1997 Oct
PMID:Fludarabine and granulocyte colony-stimulating factor (G-CSF) in patients with chronic lymphocytic leukemia. 932 81

Mitoxantrone (M) is a synthetic aminoanthraquinone with anti-leukemic activity in patients with daunorubicin (D) resistant acute leukemia. The Cancer and Leukemia Group B (CALGB) has undertaken a limited access pilot study in which M, 12 mg/m2, over 30 min, daily for 3 days, and cytosine arabinoside (Ara-C), 100 mg/m2/day by constant infusion for 7 days were used for the induction of newly diagnosed patients with AML. Responding patients were consolidated with daunorubicin, 45 mg/m2/day for 3 days, and 7 days of Ara-C. After a second consolidation identical to induction, no further therapy was given. Twenty-nine patients with a median age of 50 years (range 18-72) were entered in the study; 18 were males and 11 females. Twenty-four (83%) patients achieved CR, 1 patient achieved a PR, and 4 died in induction from leukemia-related causes. Two patients died in CR from consolidation-related neutropenic sepsis and two additional patients died in CR. Of 24 patients, 7 remain disease-free at a median follow-up interval of 8 years. The regimen is active and well tolerated. The duration of disease-free survival in responding patients is consistent with that seen in similar regimens using intensification chemotherapy without prolonged maintenance.
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PMID:Sequential mitoxantrone, daunorubicin, and cytosine arabinoside for patients with newly diagnosed acute myelocytic leukemia. 939 81

Acute myeloid leukemia following organ transplantation (PT-AML) is a rare event with only a few published cases in the literature. We present three patients who developed AML (FAB M1, M5, M4) after renal, double lung or liver transplantation. Molecular analysis detected a t(9;11) in one patient and documented the recipient origin of AML in a second patient. All patients were treated with chemotherapy. Immunosuppression was reduced to cyclosporin A (CsA) and prednisone in two patients and to prednisone alone in one patient. Two patients achieved a complete remission (CR), with a remission duration of 4.6 months in one patient, the other patient died from septicemia after 15.2 months in CR. One patient was refractory to chemotherapy and died from septicemia. This report together with the documented cases in the literature suggests that PT-AML (1) develops after a median interval of 5 years after transplantation with variable latency (range, <1-17 years); (2) is heterogeneous with respect to FAB classification; (3) shows chromosomal and molecular changes typical of therapy-related AML (t-AML: -7, +8, 11q23, inv16, t(15;17)); (4) standard chemotherapy is feasible after reduction of immunosuppression and produces a CR rate of 56% with a median remission duration of 4.6 months and an overall survival of 2.6 months; (5) the major complications are early death (25%), gram-negative septicemia, progressive disease or relapse. This review provides diagnostic and therapeutic experiences and guidelines for the management of this increasing group of post-transplant patients.
Leukemia 1999 Mar
PMID:Post-transplant acute myeloid leukemia (PT-AML). 1008 21

The aim of the study was to determine the effectiveness of 2-chlorodeoxyadenosine (2-CdA) administered in 2-h i.v. infusions in the treatment of B cell chronic lymphocytic leukemia (B-CLL) in patients 55 years old and younger. One hundred and thirteen patients received three to 10 courses of 2-CdA administered at a dose of 0.12 mg/kg daily for 5 consecutive days. Sixty-seven patients were previously treated with chlorambucil and prednisone, COP and some of them also with CHOP, and 46 were untreated. Complete remission (CR) was achieved in 21 (18.6%) (19 in untreated and two in previously treated) patients and partial response (PR) in 38 (33.6%) (23 and 15, respectively) giving an overall response rate in 52.2%. The differences in CR and overall response rate between previously treated and untreated patients were statistically significant (P = 0.001). Surface immunophenotyping by flow cytometry using dual-color staining on the peripheral blood and/or bone marrow was performed in 38 patients who responded to 2-CdA therapy. Residual disease had been demonstrated in five out of 17 (29.4%) patients who were in CR and in all 21 investigated PR patients. 2-CdA-induced thrombocytopenia occurred in 24 (35.8%) of previously treated and in 13 (28.3%) previously untreated patients (P = NS). Neutropenia was observed in eight (11.9%) and in five (10.9%) patients, respectively (P = NS). Severe infections, including pneumonia and sepsis, occurred more often in previously treated (44.8%) than untreated patients (26.1%) (P < 0.05). Twenty-seven (23.9%) patients died, 11 because of infections, five because of drug-related thrombocytopenia and hemorrhage, one because of second malignancy and eight because of disease progression. In conclusion, our results indicate that 2-CdA is an effective agent in younger patients with B-CLL, especially used as a first line therapy.
Leukemia 1999 Apr
PMID:2-Chlorodeoxyadenosine (Cladribine) in the treatment of patients with chronic lymphocytic leukemia 55 years old and younger. 1021 56

Oral mucositis is common, painful, dose-limiting toxicity of drug and radiation therapy for cancer. In granulocytopenic patients, the ulcerations which accompany mucositis are frequent portals of entry for indigenous oral bacteria often leading to bacteremias or sepsis. The complexity of mucositis as a biological process has only recently been appreciated. The condition appears to represent a sequential interaction of the oral mucosal cells and tissues, pro-inflammatory cytokines, and local environmental factors in the mouth such as microorganisms and saliva. The recognition that the pathophysiology of mucositis is a multifactorial process has presented opportunities for intervention based on biological attenuation. Interleukin-11, a pleotropic cytokine, has a range of activities which is potentially relevant to mucositis. Consequently, it has been used successfully to modify the development, severity and course of mucositis in an animal model which closely mimics the equivalent human condition.
Leukemia 1999 Jun
PMID:The biological basis for the attenuation of mucositis: the example of interleukin-11. 1036 Mar 68

To compare the antileukemic efficacy of idarubicin and mitoxantrone in elderly patients with acute myeloid leukemia (AML) and to evaluate the feasibility of autologous transplantation using PBSC after consolidation in those with a good performance status, 160 patients (median age 69 years), with AML at diagnosis, 118 of them with de novo AML and 42 with AML secondary to myelodysplastic syndrome or toxic exposure (sAML), received induction treatment with idarubicin, 8 mg/m2/day or mitoxantrone, 7 mg/m2/day, on days 1, 3, and 5, both combined with VP-16, 100 mg/m2/day on days 1 to 3 and cytarabine (araC), 100 mg/m2/day, on days 1 to 7. G-CSF, 5 microg/kg/day, was administered after chemotherapy in patients aged more than 70 years. Patients in complete remission (CR) received one course of consolidation using the same schedule as for induction except the araC administration was shortened to 5 days. Some patients younger than 70 years were then scheduled for autologous stem cell harvest on days 5 to 7 of G-CSF, 5 microg/kg/day, initiated after hematopoietic recovery from consolidation. Autologous transplantation was performed following an additional chemotherapy conditioning. Ninety-five patients (59%) achieved CR, without significant difference between the idarubicin (56% CR) and mitoxantrone (63% CR) group. There was also no significant difference in CR rate between de novo AML (63%) and secondary AML (55%) (P = 0.12). Patients aged < 70 years had 67% CR, while patients aged > or = 70 years had 49% (P = 0.02). There was no significant difference in the duration of aplasia between the two arms. Median time to neutrophil recovery was 22 days in patients who received G-CSF following induction and 27 days in patients who did not (P = 0.006). Severe extrahematologic toxicities of induction did not differ between the two arms and included sepsis (39%), diarrhea (13%), hyperbilirubinemia (8%), hemorrhage (6%) and vomiting (6%). Overall, 14 patients (9%), died from toxicity of induction. First consolidation was administered in 74 patients of whom seven (9%) died from toxicity. Nineteen patients have received transplantation. Median time to recovery of neutrophils > 0.5 x 10(9)/l was 13 days and of platelets > 50 x 10(9)/l 43 days following consolidation. There were two toxic deaths. Median disease-free survival and survival from time of achieving CR of non transplanted patients are 6 and 7 months respectively without difference between the two arms. Fourteen transplanted patients relapsed at a median of 5 months post-transplant. We conclude that this regimen is well tolerated and has a good efficacy to induce CR, without a significant difference in efficacy and toxicity between idarubicin and mitoxantrone. Intensive postinduction, including transplantation, is feasible; however, this procedure did not seem to prevent early relapse in the majority of patients. Neither the high rate of CR nor consolidation nor transplant procedure in a selected group of patients did translate into improved DFS and/or survival.
Leukemia 1999 Jun
PMID:Multicenter randomized phase II trial of idarubicin vs mitoxantrone, combined with VP-16 and cytarabine for induction/consolidation therapy, followed by a feasibility study of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia. 1036 Mar 70

The EMA86 study showed efficacy of intensive sequential chemotherapy with mitoxantrone, 12 mg/m2 day on days 1-3, etoposide, 200 mg/m2/day as a continuous infusion on days 8-10 and cytarabine (araC), 500 mg/m2/day as continuous infusion on days 1-3 and 8-10 (EMA regimen) in previously treated patients with AML. The goal of the EMA91 study was to determine whether administration of GM-CSF between the two sequences of EMA chemotherapy and during the second sequence could increase therapeutic efficacy by potentially increasing leukemic cell recruitment into the S phase of cell cycle before the second sequence. One hundred and ninety-two patients aged less than 65 years with previously treated AML received GM-CSF, 5 microg/kg/day or placebo from day 4 to day 8 of EMA chemotherapy. One hundred and twenty were refractory and 72 were in first relapse after a complete remission (CR) of more than 6 months duration. CR rates after one course of chemotherapy were 65% in the GM-CSF group (refractory: 51%; first relapse: 89%), not significantly different from the 59% CR rate (refractory: 46%; first relapse: 81%) in the placebo group. Median time to recovery of neutrophils was 38 and 37 days and median time to last platelet transfusion 32 and 32 days respectively in the GM-CSF and placebo groups. WHO grade > or = 3 non-hematologic toxicities were mainly sepsis (45% and 51%, respectively) and mucositis (34% and 31%) and did not differ between the two groups. Toxic death rate was 5% and 8%, respectively, in the GM-CSF and placebo groups. Patients achieving CR were scheduled to receive six courses of maintenance with reduced-dose EMA. Time to progression tended to be longer in the GM-CSF group (median 154 vs 115 days, progression-free rate at 18 months 33% vs 19%, P = 0.08), particularly in refractory patients (P = 0.06). However, at the current follow-up, this did not translate into a significantly longer disease-free survival and survival. Cell cycle studies showed increased recruitment of cells in the S phase between day 4 and day 8 in the GM-CSF group compared to placebo (P = 0.006). However, this did not significantly relate to prognosis in this cohort of patients. GM-CSF might marginally increase efficacy of sequential chemotherapy without increasing its toxicity in the absence of any detected relationship between this effect and observed leukemic cell recruitment into the cell cycle.
Leukemia 1999 Aug
PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF) to increase efficacy of intensive sequential chemotherapy with etoposide, mitoxantrone and cytarabine (EMA) in previously treated acute myeloid leukemia: a multicenter randomized placebo-controlled trial (EMA91 Trial). 1045 Jul 49

Cytogenetic abnormalities are used to define prognostic subgroups of acute myelogenous leukemia (AML) with respect to achieving complete remission (CR) and remaining disease free. These prognostic groups for obtaining CR were based on an induction regimen mainly using standard dose cytosine arabinoside (Ara-C) + daunorubicin (DNR). We have reviewed our experience with 122 adult patients with de novo non-M3 AML who were treated with high-dose (HD) Ara-C 3 g/m2 given over 3 h every 12 h for a total of eight doses followed by DNR 60 mg/m2 daily for 2 days. CR was obtained in 80% while 16% had refractory disease and 4% died of sepsis during hypoplasia. CR rate for favorable, intermediate and unfavorable cytogenetic groups were 87%, 79% and 62%, respectively (P = 0.32). High white blood cell count, age, FAB subtype and LDH levels did not adversely affect CR rate. Eighty-five percent of patients achieved CR with one course of treatment and 87% of complete responders were able to receive post remission therapy. High-dose Ara-C/DNR appears to offer an excellent chance of achieving remission for patients with AML including those with poor risk cytogenetics, without an increase in early toxic deaths.
Leukemia 2000 Jul
PMID:High-dose cytosine arabinoside and daunorubicin induction therapy for adult patients with de novo non M3 acute myelogenous leukemia: impact of cytogenetics on achieving a complete remission. 1091 41

Twenty-nine consecutive patients with high-risk hematological malignancy aged from 3 to 58 years underwent an unmanipulated graft from an HLA-identical sibling after an irradiation-free preparative regimen consisting of idarubicin (IDA), 21 mg/m2/day administered by continuous infusion on days -12 and -11, followed by busulphan (BU), 4 mg/kg/day orally from day -7 to -4, and cyclophosphamide (CY), 60 mg/kg/day intravenously on days -3 and -2 (IDA-BUCY2). Most clinically relevant extra-hematological regimen-related toxicities consisted of stomatitis observed in all subjects and hemorrhagic cystitis occurred in five cases (17%) within 100 days after transplant. Six patients (21%) developed a grade 2 acute graft-versus-host disease (GVHD) and three (10%) a grade 3 or 4; extensive chronic GVHD was assessed in nine of 22 (41%) evaluable patients. So far, 12 patients have died and 17 are alive, 16 of whom disease-free, 5-41 months after transplant (median, 15 months). The causes of death were related to GVHD in three patients, to sepsis in one and to disease recurrence in the remaining eight. At present, only one of nine relapsed patients is alive. For all patients the actuarial probability of survival (OS) at 1 and 2 years +/- standard error (s.e.) was 63 +/- 9% and 52 +/- 10%, respectively. The actuarial probabilities of disease-free survival (DFS), relapse and transplant-related mortality (TRM) at both 1 and 2 years +/- s.e. were 53 +/- 9%, 35 +/- 9% and 16 +/- 7%, respectively. These results are encouraging but not substantially different from those obtained in 28 patients with malignancy in advanced phase transplanted after the standard BUCY2 regimen, who had an actuarial probability of OS, DFS, relapse and TRM projected at 10 years +/- s.e. of 54 +/- 10%, 57 +/- 9%, 36 +/- 9% and 11 +/- 6%, respectively. Although the retrospective comparison between the two groups does not seem to show any advantage in the use of the IDA intensified regimen, only a prospective randomized trial could answer this question.
Leukemia 2000 Dec
PMID:Idarubicin intensified BUCY2 regimen in allogeneic unmanipulated transplant for high-risk hematological malignancies. 1118 92


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