Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because the use of cisplatin-based chemotherapy for ovarian carcinoma has not significantly improved 5-year survival rates compared with either whole-abdominal radiation (WAR) or single-agent chemotherapy, a pilot study was begun to assess the feasibility of concomitant radiation and chemotherapy. Eleven previously untreated patients with Stages III and IV ovarian carcinoma were treated concomitantly with 2000 cGy of WAR and intraperitoneal (IP) cisplatin followed by additional IP cisplatin after debulking surgery. Toxicity was moderate to severe. Sixty-four percent of patients had Grades 3 to 4 hematologic toxicity, and 36% required hospitalization for sepsis during WAR/IP cisplatin. Hematologic toxicity was less pronounced during IP cisplatin alone. All patients experienced moderate gastrointestinal toxicity. The average percentage of total body weight lost was 13.5%. Fifty-five percent of all patients demonstrated a complete clinical response to therapy, and patients with minimal postoperative residual disease fared better. One patient with persistent disease had acute nonlymphocytic leukemia (ANLL) 24 months after initial diagnosis. No patients with residual disease greater than 20 mm survived, while 50% of patients with less than 20 mm are clinically free of disease. Toxicity appears to be additive with the combination of WAR and IP cisplatin. Therapeutic efficacy was comparable with standard chemotherapy regimens, but no therapeutic or survival advantages were demonstrated with the use of this treatment protocol.
 ...
PMID:Concomitant whole-abdominal radiation and intraperitoneal chemotherapy in advanced ovarian carcinoma. A pilot study. 202 52

DNA-fingerprint (DNA-F) analysis of leukemic cells can reveal new restriction fragments in some patients with acute leukemia. These genomic alterations can be used as molecular markers of residual disease. In this study, the sensitivity and clinical use of DNA-F analysis was evaluated. The detection limit for minority DNA was studied in six cell dilution series. An increasing ratio (1-20%) of cells was mixed with cells from another individual; intense extra bands could be identified in the DNA extracted from cell mixtures containing 5% of minority cells. In clinical samples from five of 19 ALL and six of 18 AML cases, the DNA-F of blast cells had new bands which could be followed during remission; in two cases the extra bands were intense enough to be detected at less than 5%. Studies of 37 patients with leukemia demonstrated that DNA-F analysis provides an additional tool for the detection of residual disease in acute leukemia.
 ...
PMID:DNA fingerprinting in the detection of residual disease in acute leukemia. 203 65

The possibilities for studying minimal residual disease (MRD) in human acute myelocytic leukemia (AML) are limited. Animal models are, therefore, indispensable for gaining insight into the characteristics of leukemia growth during the MRD phase. Studies were done to compare AML to acute myelocytic leukemia in the Brown Norway rat (BNML). The BNML model exhibited a high degree of similarity to human AML with regard to its general growth characteristics, its cell kinetic parameters, its biophysical parameters and its response to chemotherapy. This implied that studies of the BNML model have predictive value for clinical application. In the BNML model a number of independent methods are available to quantify the number of leukemic cells, i.e., indirectly by means of various bioassays or directly by using monoclonal antibody labeling and flow cytometry. Studies of the BNML model in relation to the understanding of various aspects of MRD in leukemia are discussed in this concise review. Insight has been obtained with regard to the kinetics of MRD; the efficacy of certain treatment modalities, e.g., cytostatic drug treatment with or without total body irradiation to eradicate MRD; the efficacy of various methods for eliminating residual leukemic cells from autologous marrow grafts; the emergence of drug resistance during MRD; and the progression of residual disease during the remission phase ultimately leading to a relapse and the implications of these observations for staging leukemia patients during the phase of MRD.
 ...
PMID:Minimal residual disease in leukemia: studies in an animal model for acute myelocytic leukemia (BNML). 240 82

DNA-fingerprint (DNA-F) analysis, based on the polymorphism of the tandem repeats of minisatellite areas in human genome, has a capacity to reveal minor changes in dispersed areas of human genome. In this study we have applied DNA-F analysis to the detection of differences between leukemic phase and remission in acute myeloid leukemia (AML). In order to identify normal and leukemic cell populations we used two molecular probes: Jeffreys' minisatellite probes 33.6 + 33.15 and M13 wild-type phage probe. Comparison of varying minisatellite fragments between remission and diagnosis/relapse was performed by Southern blot hybridization in 21 patients with AML. The results demonstrate that Southern hybridization with minisatellite probes can detect differences in DNA-fingerprints between leukemic phase and remission in 44% of AML patients. Thus differences in DNA-fingerprinting provides a new molecular marker, which can be useful in the detection of residual disease as well as in the study of the pathogenesis of AML.
 ...
PMID:New molecular marker in AML: DNA-fingerprint differences between leukemic phase and remission in acute myeloid leukemia. 257 52

The effect of lymphokine-activated killer (LAK) cells on the in vitro clonogenic capacity of acute myeloid leukemia (AML) blasts was investigated in a semisolid medium assay. The leukemic clonogenic capacity of 11 AML cases, selected on the basis of their ability to grow in vitro, was highly reduced following overnight preincubation with LAK effectors. The degree of colony inhibition, which ranged between 66% and 98% (mean 83.8% +/- 11.4 SD), was quantitatively greater than by 51Cr release, which gave rise to lytic values between 5% and 65% (mean 43.2% +/- 19.2 SD). The demonstration that the clonogenic inhibition was still induced following a shorter pre-incubation period (4 hours) suggests that the effect is unlikely to be due only to the generation of cytotoxic activity during the incubation time. The possibility that LAK cells may be employed in the management of residual disease is strengthened by the evidence that the clonogenic potential of samples containing as few as 20% and 14.3% leukemic cells could be almost completely abolished by LAK effectors. These findings further point the possible role of adoptive immunotherapy with interleukin 2/LAK cells in the treatment of patients with acute leukemia.
 ...
PMID:Lymphokine-activated killer (LAK) cells inhibit the clonogenic growth of human leukemic stem cells. 278 77

A predictable increase in the proliferative rate of malignant cells remaining after initial cytoreduction in vivo forms the rationale for timed sequential therapy (TST) with 1-B-D-arabinofuranosylcytosine (ara-C) for adult acute myelogenous leukemia (AML). The relationship between in vivo leukemic cell growth, intracellular ara-C metabolism, and clinical response to ara-C-containing TST was evaluated by comparing AML marrow cell growth kinetic and biochemical pharmacologic determinants obtained before therapy (day 0) and at the predicted peak of in vivo postdrug residual tumor proliferation (day 8). Serial measurements of DNA synthesis and net intracellular ara-C metabolism demonstrated marked increases in both determinants in day 8 residual tumor when compared with the pretreatment cells for newly diagnosed adults achieving complete remission but not for TST-refractory patients. The interrelationship of AML cell proliferation and biochemical pharmacology together quantitate cytotoxicity measured by both achievement and duration of remission and serve to predict eventual clinical outcome in response to TST with ara-C where both growth and favorable pharmacokinetics are intrinsic to the success of the drug schedule.
 ...
PMID:In vivo cell growth and pharmacologic determinants of clinical response in acute myelogenous leukemia. 291 Mar 62

In the present study, we demonstrate that resting and rIL-2-activated NK cells had no inhibitory effects on peripheral blood-derived hematopoietic progenitor (HP) cells. Peripheral blood HP cells were similar to bone marrow progenitors in phenotype and clonogenic colony formation capabilities. Peripheral blood HP cells could be cocultured in vitro with rIL-2-activated autologous NK cells for 3 d without adverse effects on the HP cells. Acute myelogenous leukemia patients in stable remission were shown to have normal percentages of NK cells and elevated percentages of peripheral blood HP cells. NK cells from most of these patients could be activated with rIL-2 to lyse fresh uncultured tumor cells as well as autologous leukemia cells without effecting the peripheral blood HP cells. These results suggest that rIL-2-activated NK cells may be used to purge peripheral blood HP cell preparations of residual tumor cells before hematopoietic reconstitution.
 ...
PMID:The effects of recombinant interleukin 2-activated natural killer cells on autologous peripheral blood hematopoietic progenitors. 326 Sep 39

Childhood nonlymphocytic leukemia comprises a minority (25%) of pediatric leukemia cases, yet contributes a significant proportion of overall leukemia mortality. Improvements in supportive care (antibiotics, antifungals, nutrition, and blood products) along with aggressive induction therapies have significantly improved remission induction rates over the past two decades. Ideal treatment to completely eliminate residual disease following remission is not yet known. In most series, only one out of three patients are long-term survivors of this disease. Recent advances in allogeneic bone marrow transplantation and improved techniques for autologous engraftment leave promise for significant improvements in postinduction disease control. Biologic studies of surface immunophenotype have contributed to our understanding of the heterogeneity of this family of disorders and allowed identification and characterization of leukemias of mixed myeloid/lymphoid lineage. Karyotype studies have identified important subsets of ANLL with distinctive clinical and biologic properties, for which tailored therapies someday may be developed. In addition, studies of oncogenes provide insight into regulation of leukemic hematopoiesis with potential of identifying future methods to regulate proliferation of the leukemic clone.
 ...
PMID:Biology and therapy of childhood acute nonlymphocytic leukemia. 328 Nov 4

Two patients with acute nonlymphocytic leukemia (ANLL) (FAB-M4) and t(6;9)(p23;q34) are described. Immunological marker analysis revealed a phenotype of HLA-DR+/partly terminal deoxynucleotidyl transferase (TdT)+/CD13+ in both cases and CD33 positivity in one. The expression of CD13 and CD33 by TdT-positive cells was demonstrated by double immunofluorescence staining. Although it has been postulated that TdT plays a role in gene rearrangement, Southern blot analysis performed in one leukemia revealed that both the T cell receptor beta chain genes and the immunoglobulin heavy chain genes were in germ line configuration. Since we could not detect CD13+/TdT+ cells and CD33+/TdT+ cells in control bone marrow samples, double marker analysis was used to detect low numbers of residual leukemic cells during follow-up of one patient. A gradually increasing percentage of CD33+/TdT+ cells was detected in the bone marrow in a period of 6 months before hematological relapse. Although the t(6;9) may not be correlated to a specific French-American-British subtype, it may be associated with TdT-positive ANLL. Since TdT-positive ANLL seems to have a poor outcome, detection of TdT expression in ANLL patients is particularly important for diagnostic purposes. In addition, our results indicate that double immunological marker analysis for a myeloid marker and TdT allows detection of residual disease during follow-up.
 ...
PMID:Translocation (6;9) may be associated with a specific TdT-positive immunological phenotype in ANLL. 334 92

Twenty-two patients with relapsed or refractory acute leukemia received 31 treatment courses of mitoxantrone (10 to 12 mg/m2/d) as a one-hour infusion for five days. Seven of the 13 patients who had greater than or equal to 95% reduction in the leukemia cell mass, calculated using the bone marrow examination on day 6, achieved a complete remission (CR). These remissions lasted up to 14 months without additional therapy. There were no CRs among the 18 patients who had less than 95% cytoreduction by day 6. The sequential addition of 5-azacytidine (200 mg/m2/d) for three days in those patients with residual disease on day 6 provided little additional benefit. Nonhematological toxicity from mitoxantrone was mild, although fever and infection were common. A new high-performance liquid chromatography (HPLC) assay was used to describe the clinical pharmacokinetics of mitoxantrone. Neither clinical response nor toxicity was strongly correlated with the peak plasma mitoxantrone concentration on the first day (mean +/- SD, 510 +/- 206 ng/mL), nor the area under the concentration-time curve (484 +/- 229 ng X h/mL), nor the systemic clearance (405 +/- 124 mL/min/m2). Mitoxantrone causes rapid cytoreduction in acute nonlymphocytic leukemia (ANLL), but the optimal dose and schedule remain to be determined.
 ...
PMID:A clinical and pharmacokinetic study of mitoxantrone in acute nonlymphocytic leukemia. 354 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>