Biomedical subjects

S Creech

Publications and source records attributed to S Creech.

7 recordsLinked to original sources

PubMed2005

Impact of tumor volume-directed involved field radiation therapy integrated in the management of recurrent ovarian cancer.

OBJECTIVES: Assess the role of involved field radiation therapy (IFRT) in recurrent ovarian cancer. METHODS: Thirty-five patients with a diagnosis of epithelial ovarian cancer received radiation therapy at LUMC between 1991 and 2001. Of these, 20 received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation following debulking surgery or as attempted salvage if unresectable) and form the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Eleven patients had optimal debulking of their recurrences prior to radiation. IFRT was primarily with external beam (median dose 50.4 Gy). Appropriate statistical analyses evaluated association among disease-free (DFS), overall survival (OS), local recurrence-free (LRFS), and various prognostic factors. LRFS was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. RESULTS: Of 20 patients, 17 had a complete response after RT. The actuarial LRFS, OS, and DFS at 5 years from date of radiation were 66%, 34%, and 34%, respectively. The LRFS at 3 years was 89% for those with optimal resection vs. 42% for those with gross residual/unresectable tumor, which was significantly better (P = 0.04). The corresponding 3-year DFS was 72% vs. 22% and 5-year OS was 50% vs. 19%, respectively. Acute complication of RT was mild, half had Grade 1-2 gastrointestinal (GI) toxicity, three patients had Grade 3-4 late GI effects. CONCLUSION: IFRT is effective in controlling localized recurrences of ovarian cancer, especially after they are optimally debulked (89% local control and 50% 5-year overall survival in this subgroup), and is relatively well tolerated in these heavily pretreated patients.

Adult↗

PubMed2004

Analysis of remobilization success in patients undergoing autologous stem cell transplants who fail an initial mobilization: risk factors, cytokine use and cost.

Inadequate stem cell mobilization is seen in approximately 25% of patients undergoing autotransplantation for hematologic malignancies. Remobilization strategies include chemotherapy/cytokine combinations or high-dose cytokines alone or in combination. From 1/1997 to 7/2002, we remobilized 86 patients who failed an initial mobilization (median total CD34=0.72 x 10(6)/kg) in sequential cohorts using high-dose G-CSF (32 microg/kg/day) or G-CSF(10 microg/kg/day)+GM-CSF (5 microg/kg/day). No difference in CD34/kg yields were seen (G-CSF alone: 2.2 x 10(6) and G-CSF+GM-CSF 1.6 x 10(6)) in the median 3 aphereses performed (P=0.333). Of the 86, 23 (27%) failed the second mobilization; 14 were remobilized again (yield=1.5 x 10(6) CD34/kg; three aphereses). Of the 86, 93% went to transplant: three progressed, and three had inadequate stem cells. Significant risk factors for a failed remobilization were: number of stem-cell-damaging regimens (P=0.015), time between last chemotherapy and first mobilization (P=0.028), and higher WBC at initiation of first mobilization (P=0.04). High-dose G-CSF (32 microg/kg/day) was more costly @ USD $9,016, vs $5,907 for the G-CSF+GM-CSF combination (P<0.001). Most patients failing an initial mobilization benefit from a cytokine only remobilization. Lower cost G-CSF+GM-CSF is as effective as high-dose G-CSF.

Adult↗

PubMed2001

Alterations in IRF1/IRF2 expression in acute myelogenous leukemia.

The interferon response genes 1 and 2 have been shown to be involved in the regulation of differentiation and proliferation of cells of the myeloid series, with the former functioning as an anti-oncogene and the latter as an oncogene. In the study described here, the levels of expression of these two genes and the ratio of their expression were compared in AML and normal marrow. The ratio of gene expression was significantly less in AML marrow cells as compared to normal marrow cells [med ratio = 1.33 vs. 2.97, P = 0.003]. While the expression ratio was unaffected by the presence or absence of either ras or fms mutations, p53 mutations were associated with higher IRF1:IRF2 expression ratios that wt p53 genes [med = 1.701 vs. 1.135, P = 0.014]. Given the functional characteristics and the competitive nature of these two genes, it is possible that leukemic transformation is associated with a fall in IRF1:IRF2 ratios. Finally, the administration of IL4 can result in the normalization of the IRF1:IRF2 ratio in the marrow cells of some patients with AML.

Adult↗

PubMed2001

Poor prognosis acute myelogenous leukemia: 3--biological and molecular biological changes during remission induction therapy.

This is the third paper in a series which describes a new remission induction regimen for patients with 'poor prognosis' acute myelogenous leukemia (AML). Twenty-four patients were treated with two one day pulses of chemotherapy separated by 96 h. Each pulse consisted of two doses of cytarabine and a single dose of mitoxantrone. Amifostine was administered three times a week after the second pulse of chemotherapy until treatment outcome became known. The first paper described the outcome of treatment while the second described the relationship of treatment outcome to the pretherapy characteristics of the leukemia. This paper describes the changes in the leukemia cells which occur during remission induction therapy. While only a limited number of specimens were available for each post treatment study, the studies demonstrated a profound fall in blood counts, BM cellularity, and telomerase activity in leukemia cells after pulse #1 of treatment. This fall was usually accompanied by a coordinate rise in IL6, TNFalpha, and IL1beta transcripts within the AML cells which survived chemotherapy. High levels of telomerase activity in the day 5 marrow was correlated with high levels of IL1beta transcripts which in turn were associated with treatment failure ascribable to resistant disease.

Antineoplastic Agents↗

PubMed2001

P15INK4B gene methylation and expression in normal, myelodysplastic, and acute myelogenous leukemia cells and in the marrow cells of cured lymphoma patients.

P15INK4B methylation and expression was studied in bone marrow cells obtained from normal individuals, from patients who had been cured of lymphoma, and from patients with either MDS or AML. The level of p15 methylation was very low in normal BM cells and in CD34+ and CD34- subpopulations (0-6.5%; med, = 2.5%). P15INK4B transcripts were present in each of these cell populations. In contrast, methylation was the usual situation in MDS and AML marrows. The presence of methylation of the p15INK4B gene did not always indicate an absence of expression nor was expression always present if methylation was absent. P15INK4B methylation was studied in the marrows of nine patients (one studied twice) who had been cured of lymphoma and in whom hemopoiesis was believed to be normal. Increased methylaton was present in all 10 marrows. These data indicate that p15INK4B methylation is likely to be a very early event in the development of the secondary hematologic disorders.

Adult↗

PubMed2000

Poor prognosis acute myelogenous leukemia: 1 - response to treatment with high dose cytarabine/mitoxantrone/ethyol @ (Amifostine).

Twenty patients with poor prognosis AML and four patients in the blastic phase of a myeloproliferative disorder were treated with two 'pulses' of therapy each consisting of two doses of high dose araC (separated by 12 h) followed by a single dose of mitoxantrone. The pulses were separated by 96 h. Amifostine was then administered tiw. The median age of the population was 68 years with 88% of patients having had either a prior MDS, MPD or toxic exposure. The acute leukemia of 58% of patients either entered a CR or reverted to preleukemic state. For patients under 70 years of age, treatment produced 62% CRs with a leukemia free decision marrow in 77%. For patients over 70 years the CR rate was 27% with 36% of patients having a leukemia free decision marrow.

Adult↗

PubMed1990

Kate's comeback.

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Adult↗