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Biomedical subjects

E Agura

Publications and source records attributed to E Agura.

8 recordsLinked to original sources
PubMed2005

Hematopoietic cell transplantation from HLA-identical sibling donors after low-dose radiation-based conditioning for treatment of CML.

A total of 24 patients (median age 58; range, 27-71 years) with chronic myeloid leukemia (CML) in first chronic (CP1) (n=14), second chronic (n=4), or accelerated phase (n=6) who were not candidates for conventional hematopoietic cell transplantation (HCT), received nonmyeloablative HCT from HLA-matched siblings a median of 28.5 (range, 11-271) months after diagnosis. They were conditioned with 2 Gy total body irradiation (TBI) alone (n=8) or combined with fludarabine, 90 mg/m(2) (n=16). Postgrafting immunosuppression included cyclosporine and mycophenolate mofetil. All patients initially engrafted. However, 4 of 8 patients not given fludarabine experienced nonfatal rejection while all others had sustained engraftment. With a median follow-up of 36 (range, 4-49) months, 13 of 24 patients (54%) were alive and in complete remission. There were five (21%) deaths from nonrelapse mortality, one (4%) during the first 100 days after transplant. The proportions of grade II, III, and IV acute GVHD were 38, 4, and 8%, respectively. The 2-year estimate of chronic GVHD was 32%. The 2-year survival estimates for patients in CP1 (n=14) and beyond CP1 (n=10) were 70 and 56%, respectively. This study shows encouraging remission rates for patients with CML not eligible for conventional allografting.

Adult↗
PubMed2001

Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is followed by profound immunodeficiency. Thymic function is necessary for de novo generation of T cells after HSCT. Circulating CD45RA(+) naive T-cell levels are predictive of antigen-specific T-cell responses in the absence of graft-versus-host disease (GVHD). These T cells may not represent recent thymic emigrants, since naive T cells may maintain this phenotype if not antigen-activated. To accurately measure thymic output after HSCT and determine the factors that influence thymic function, T-cell receptor excision circles (TRECs) were examined in CD4(+) and CD8(+) cells from a cross-section of patients following HSCT. TREC levels rose weeks after HSCT and could be detected in patients 6 years after HSCT. TREC levels correlated with the frequency of phenotypically naive T cells, indicating that such cells were not expanded progeny of naive T cells present in the donor graft. Chronic GVHD was the most important factor that predicted low TREC levels even years after HSCT. Patients with a history of resolved GVHD had decreased numbers of TREC, compared with those with no GVHD. Because few adults had no history of GVHD, it was not possible to determine whether age alone inversely correlated with TREC levels. Recipients of cord blood grafts had no evidence of decreased TREC induced by immunosuppressive prophylaxis drugs. Compared with unrelated donor grafts, recipients of matched sibling grafts had higher TREC levels. Collectively, these data suggest that thymopoiesis is inhibited by GVHD. Larger studies will be needed to determine the independent contributions of age and preparative regimen to post-transplant thymopoietic capacity.

Adolescent↗
PubMed1999

Randomized, double-blind, placebo-controlled trial to evaluate the hematopoietic growth factor PIXY321 after moderate-dose fluorouracil, doxorubicin, and cyclophosphamide in stage II and III breast cancer.

PURPOSE: To measure the effect of PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 S. cerevisiae fusion protein) on the incidence, duration, and complications of neutropenia and thrombocytopenia after moderate-dose fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 750 mg/m(2) (FAC) chemotherapy in patients with stage II and III breast cancer. PATIENTS AND METHODS: In this multicenter, randomized, double-blind placebo-controlled trial, 71 women were to receive four 21-day cycles of treatment with moderate-dose FAC chemotherapy by short intravenous infusion on day 1, followed by either placebo or PIXY321 (375 microg/m(2) subcutaneously twice a day) on days 3 to 15. All patients were to receive prophylactic oral ciprofloxacin when the absolute neutrophil count was less than 1,000/microL. RESULTS: PIXY321 significantly reduced the incidence and duration of grade 3 and grade 4 neutropenia in cycles 1 and 2 and the duration of grade 3 neutropenia in cycles 1 through 4. In cycles 3 and 4, grade 3 thrombocytopenia was significantly more common with PIXY321 (P <.05). Two patients, both in the PIXY321 group, required platelet transfusions. Fever and hospitalization for intravenous antibiotics were significantly more common in the PIXY321 group during cycle 1 only. More patients in the PIXY321 group achieved hematologic recovery by day 22 in cycles 1 through 3, and time to recovery was significantly shorter with PIXY321 in all cycles. FAC dose intensity was roughly 2% higher in the PIXY321 group (P = NS). Nonhematologic events of any intensity occurring with significantly greater overall frequency in the PIXY321 group included injection-site reactions, fever, chills, abdominal pain, and arthralgia. No patient died on study or within 30 days of her last dose of study drug. CONCLUSION: PIXY321 decreased the incidence and duration of FAC-induced grade 3 and 4 neutropenia in cycles 1 and 2 and significantly shortened the time to hematologic recovery in all cycles. However, it produced more systemic toxicity as well as thrombocytopenia in cycles 3 and 4.

Adenocarcinoma↗
PubMed1996

Allogeneic blood cell transplantation without posttransplant colony-stimulating factors in patients with hematopoietic neoplasm: a phase II study.

PURPOSE: There is limited experience with allogeneic blood cell transplantation (BCT). In an earlier pilot study, the combination of bone marrow and blood did not produce severe acute graft-versus-host disease (GVHD). We now report the results of a phase II study using blood stem cells alone in 19 patients. PATIENTS AND METHODS: The median age was 40 years. All patients had hematopoietic malignancies and received transplants from HLA-identical sibling donors. GVHD prophylaxis consisted of cyclosporine plus prednisone. Posttransplant colony-stimulating factors were not administered. Donors were mobilized with subcutaneous granulocyte colony-stimulating factor (G-CSF; 16 microg/kg/d) for 5 days. Apheresis was performed on 2 consecutive days. RESULTS: The median cell content of the two apheresis was 11.9 x 10(8) WBC/kg, 3.2 x 10(8) CD3/kg, and 8.3 x 10(6) CD34/kg. The median time to achieve an absolute neutrophil count (ANC) > or = 500/microL was 13 days, and 14 days to a platelet count > or = 50,000/microL. All patients engrafted. Platelet recovery was faster in marrow historic control groups. Blood cells in all tested cases contained more than 95% donor cells on day 30. The actuarial incidence of acute GVHD was 37%, and 13% for grade II-IV GVHD. Limited, corticosteroid responsive, chronic GVHD developed in 33% of assessable patients. At a median follow-up of 192 days, actuarial survival was 75%. CONCLUSION: Transplantation of a high number of stem cells may lead to rapid engraftment without the use of posttransplant colony-stimulating factors. GVHD does not appear to be more severe than in similarly treated patients undergoing bone marrow transplantation. For allogeneic transplantation, mobilized blood cell collections are an alternative to bone marrow collections.

Adult↗
PubMed1993

Cyclophosphamide cardiac injury mimicking acute myocardial infarction.

We report a patient in whom cyclophosphamide (CY) caused damage to the heart that was manifested by ST segment elevation and marked elevation of serum cardiac isoenzymes and mimicked myocardial infarction. Post-mortem examination did not reveal any local vascular event (e.g. thrombus or spasm) and suggested diffuse myocardial injury secondary to CY.

Adult↗
PubMed1989

Rare occurrence of N-ras point mutations in Philadelphia chromosome positive chronic myeloid leukemia.

Point mutations of the N-ras oncogene are relatively common in acute myelogenous leukemia (AML) cells, occurring in some 25% to 50% of patient samples. We used a technique involving the direct nucleotide sequencing of in vitro amplified N-ras genomic fragments to determine the frequency of N-ras point mutations in chronic myeloid leukemia (CML) cells at various stages of the disease. This approach will detect N-ras point mutations in a mixed population of cells if the mutation is present in 25% or more of the cells. We could not demonstrate any point mutation at N-ras codons 12,13 or 59-63 in any of the 44 CML cases analyzed, which included 21 blast crisis samples. In contrast with AML N-ras point mutations are exceedingly rare in CML.

Gene Rearrangement↗
PubMed1988

Endotoxin-associated protein: a potent stimulus for human granulocytopoietic activity which may be accessory cell independent.

Proteins coextracted with endotoxin, termed endotoxin-associated protein (EAP), have been shown to exert interleukin 1-like activities. The present studies demonstrate that EAP also exerts potent granulopoietic colony-stimulating activity (CSA) on human peripheral blood and bone marrow progenitor cells, comparable to that seen with various types of conditioned media. The CSA observed with EAP appeared to be heat (100 degrees C, 30 min) and trypsin resistant and partially pronase resistant. Similar resistance was observed with the porin proteins of the outer membrane of gram-negative bacteria, and similar CSA activity was observed with a purified porin preparation of Neisseria gonorrhoeae. The CSA of EAP could be demonstrated in human peripheral blood and bone marrow leukocytes rigorously depleted of monocytes, T lymphocytes, and B lymphocytes by treatment with specific monoclonal antibodies and complement.

Antigen-Presenting Cells↗