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Biomedical subjects

E D Thomas

Publications and source records attributed to E D Thomas.

At least 73 records · Page 4Linked to original sources
PubMed1990

Use of recombinant human granulocyte-macrophage colony-stimulating factor in graft failure after bone marrow transplantation.

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was evaluated in 37 patients with marrow graft failure after allogeneic (n = 15), autologous (n = 21), or syngeneic (n = 1) bone marrow transplantation. rhGM-CSF was administered by 2-hour infusion at doses between 60 and 1,000 micrograms/m2/d for 14 or 21 days. At doses of less than 500 micrograms/m2, rhGM-CSF was well-tolerated and did not exacerbate graft-versus-host disease in allogeneic transplant recipients. No patient with myelogenous leukemia relapsed while receiving rhGM-CSF. Twenty-one patients reached an absolute neutrophil count (ANC) greater than or equal to 0.5 x 10(9)/L within 2 weeks of starting therapy while 16 did not. None of seven patients who received chemically purged autologous marrow grafts responded to rhGM-CSF. The survival rates of GM-CSF-treated patients were significantly better than those of a historical control group.

Adolescent↗
PubMed1990

Cytomegalovirus infection after autologous bone marrow transplantation: occurrence of cytomegalovirus disease and effect on engraftment.

Epidemiologic and clinical characteristics of cytomegalovirus (CMV) infection and disease were analyzed retrospectively in 159 autologous marrow transplant recipients. The probability of CMV infection by day 100 after transplant was 22.5% in patients seronegative to CMV before transplant versus 61.1% in seropositive patients (P less than .0001 by logrank test). Multivariate analysis identified positive pretransplant CMV serology as the only definable risk factor for CMV infection (relative risk 1.4, P less than .0001). CMV pneumonia developed in 11 patients at a median time of 100 days after transplant and was fatal in nine cases. CMV pneumonia was associated with significantly decreased probability of survival by day 100 after transplant (relative risk of death of 16.7, P less than .0001). In contrast to earlier reports, CMV infection had no significant effect on the rapidity of platelet or neutrophil recovery after transplant as assessed by time-dependent multivariate analysis. Because the incidence of severe CMV disease is not negligible after autologous marrow transplantation, preventive measures against CMV infection are warranted, as in allogeneic marrow transplantation.

Adult↗
PubMed1990

Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma.

We analyzed the relevance of HLA incompatibility to acute graft-versus-host disease, relapse, and survival in 281 patients with hematologic neoplasms who underwent bone marrow transplantation. Each patient received marrow from a family member who shared one HLA haplotype with the patient but differed to a variable degree for the HLA-A, -B, and -D antigens of the haplotype not shared; 29 were phenotypically identical, 119 were incompatible for one locus, 104 for two loci, and 29 for three loci. These 281 patients were compared with 967 patients who received marrow from siblings with identical HLA genotypes. All patients were treated with cyclophosphamide and total-body irradiation followed by the infusion of unmodified donor marrow cells. Occurrence of severe acute graft-versus-host disease was evaluated in patients who achieved sustained engraftment. In recipients of haploidentical grafts occurrence of severe acute graft-versus-host disease was associated with (1) graft-versus-host disease prophylaxis containing the combination of methotrexate plus cyclosporine versus standard methotrexate, relative risk = 0.35; 95% confidence interval, 0.21-0.57, p less than 0.0001; and (2) the degree of recipient HLA incompatibility, relative risk = 1.95 for each locus incompatible; 95% confidence interval, 1.52-2.50, p less than 0.0001; (3) patient age, relative risk = 1.23 per decade; 95% confidence interval, 1.05-1.44, p = 0.0094. Acute graft-versus-host disease was associated with lower leukemic relapse after transplant in patients with acute lymphocytic leukemia, and chronic graft-versus-host disease was associated with lower relapse after transplant for acute nonlymphocytic leukemia in relapse or chronic myelogenous leukemia in blast crisis. After transplantation for acute nonlymphocytic leukemia in remission, the rate of leukemic relapse was 22% in 61 recipients of "one-locus" (A, B, or D)-incompatible grafts compared to 37% in 561 recipients of HLA-identical sibling grafts. Survival was decreased as the degree of HLA disparity increased. Survival of "one-locus"-incompatible transplant recipients, however, was equivalent to that of HLA-identical sibling transplant recipients.

Bone Marrow Transplantation↗
PubMed1990

Secondary T-cell lymphoproliferation after marrow transplantation.

Secondary lymphoproliferative syndromes in immunosuppressed patients have been characterized as polyclonal or monoclonal B-lineage disorders nearly always associated with Epstein-Barr virus (EBV) infection. The authors now report three patients with a distinctly different lymphoproliferative syndrome. Two patients with common acute lymphoblastic leukemia antigen (CALLA) (CD10)-positive acute lymphoblastic leukemia and one patient with acute myelogenous leukemia, respectively, received high-dose chemoradiotherapy followed by marrow transplantation from either an HLA-identical sibling or HLA-mismatched parent. All three patients developed severe graft-versus-host disease (GVHD), requiring immunosuppressive treatment with corticosteroids. A secondary malignant T-cell lymphoproliferation occurred 2, 21, and 43 months, respectively, after marrow transplantation. In all three cases the lymphoid cells expressed T-cell surface antigens and were morphologically and immunophenotypically distinct from the malignant cells present before transplantation. One tumor was of host cell origin, one was probably of donor origin, and the tumor origin in the third case could not be determined. The authors were unable to find any evidence for EBV, human T-cell lymphotropic virus type I or II, human immunodeficiency virus, or human herpesvirus 6.

Adolescent↗
PubMed1990

Stem cell selection--clinical experience.

The ability to isolate large numbers of hematopoietic progenitors will facilitate an understanding of the growth and differentiation of bone marrow. Furthermore, isolating hematopoietic progenitors will have widespread clinical applications to autologous marrow transplantation, allogeneic marrow transplantation, gene therapy, and in vitro marrow expansion. With the development of avidin-biotin immunoadsorption, it is now feasible to isolate large numbers of these progenitor cells for clinical purposes. Successful hematopoietic reconstitution has been demonstrated in lethally irradiated baboons transplanted with CD34+ cells isolated by immunoadsorption with the anti-CD34 antibody 12-8. Recent studies have shown that CD34+ cells enriched from the marrow of patients with metastatic breast cancer can be used for autologous marrow transplantation.

Animals↗
PubMed1990

Canine models of bone marrow transplantation.

Progress in experimental bone marrow transplantation in dogs has provided for the direct transfer of research data to the clinical setting and the therapeutic application of marrow grafting to a variety of human diseases. Animal models of total body irradiation, engraftment and graft-versus-host disease are still needed to solve the existing clinical problems of marrow transplantation. Therefore, work in various canine model systems continues to be of interest. Pet dogs with spontaneously occurring lymphomas are used to study the clinical parameters necessary for applying the technique of transplanting their own marrow (autologous), in conjunction with high dose radiation and/or chemotherapy, to human patients with cancer. A major consideration in the successful transplantation of donor bone marrow (allogeneic) is overcoming histocompatibility barriers to assure engraftment and the prevention of graft-versus-host disease, a major limiting aspect of clinical marrow transplantation. Chemicals, radiation, radiotherapeutic techniques, antisera and monoclonal antibodies have been and continue to be developed in laboratory bred dogs. These approaches suppress the immune system either nonspecifically by ablation of immune reactive tissue, or specifically by affecting certain types of immune reactive cells. Parameters such as clinical effectiveness (engraftment or prevention of graft-versus-host disease), immune reconstitution and undesirable side affects in long-term survivors are all used to determine whether new technology can be transferred from preclinical canine studies to human bone marrow transplantation protocols.

Animals↗
PubMed1990

Positive selection of hematopoietic progenitors from marrow and peripheral blood for transplantation.

The ability to obtain large numbers of purified hematopoietic progenitors (HPC) will facilitate the understanding of elements that influence the growth and differentiation of bone marrow. Furthermore, HPC isolation will have direct application to autologous marrow transplantation (AMT) for malignancies as well as facilitate the transfer of genes in marrow cells for the correction of genetic disorders. The transplantation of HPC will help delineate the cells or factors responsible for graft rejection and graft-versus-host-disease. Or several techniques that have been utilized for the separation of HPC, only the avidin-biotin immunoadsorption (ABIA) method has been shown capable of separating the number of cells required for large animals and man. The application of this technique to AMT in man requires the identification of an antigen found predominantly on HPC in peripheral blood or marrow but not on malignant cells that could potentially contaminate bone marrow. Studies have demonstrated that the CD34 antigen is expressed by the majority of human marrow HPC measured in long-term marrow culture and is expressed on cells capable of autologous engraftment in lethally irradiated baboons. Although the CD34 antigen is not detectable by FACS analysis on peripheral blood cells, ABIA can enrich for such cells. The CD34 antigen is not detected on cells from patients with breast cancer or neuroblastoma thus allowing clinical studies to proceed. Preliminary results suggest that CD34(+)-enriched cells are depleted of tumor cells and are capable of autologous reconstitution in man.

Antigens, CD↗
PubMed1989

Analysis of the origin of marrow cells in bone marrow transplant recipients using a Y-chromosome-specific in situ hybridization assay.

A Y-chromosome-specific in situ hybridization assay was used to assess the frequency with which host bone marrow cells are retained after marrow grafting. The majority of patients (74%) showed the presence of both host and donor marrow cells when assayed 14 days after transplant. By 84 days posttransplant only 4% of the patients retained host marrow cells. Only 1 of 19 evaluable patients analyzed over 1 year posttransplant showed minimal retention of host cells. No statistical correlation was found between retention of host cells posttransplant and the development of relapse or acute or chronic graft-versus-host disease. Pretransplant conditioning regimen, HLA-matching, diagnosis, disease status at transplant, ABO-matching, and patient age also showed no correlation with the retention of host cells posttransplant.

Bone Marrow Cells↗
PubMed1989

Host metaphases after chemoradiotherapy and allogeneic bone marrow transplantation for acute nonlymphoblastic leukemia.

The post-transplant cytogenetic data were reviewed for 191 recipients of sex-mismatched marrow after conditioning with chemoradiotherapy as treatment for acute nonlymphoblastic leukemia. Host metaphases were detected transiently in unstimulated marrow from 12/184 patients and in PHA-stimulated peripheral blood from 18/140 patients during the first 100 days after transplantation. Of the 14 patients with HM who survived more than 150 days, five have relapsed, and nine are alive and in remission 509-1783 days after detection of HM. There was no significant correlation between transient detection of HM and pretransplant remission status, HLA matching, radiation regimen or graft-vs-host disease. We conclude that transient detection of HM by conventional cytogenetics is not related to any single peritransplant parameter and does not predict relapse.

Bone Marrow↗
PubMed1989

Acute renal failure following bone marrow transplantation: a retrospective study of 272 patients.

To assess the incidence, risk factors, and course of acute renal failure (ARF) following bone marrow transplantation (BMT), a retrospective analysis of 272 patients receiving transplants at the Fred Hutchinson Cancer Research Center during 1986 was undertaken. The patients were divided into three groups: group 1, hemodialysis requiring ARF; group 2, mild renal insufficiency (doubling of serum creatinine, Scr, but no dialysis); group 3, relatively normal post-BMT renal function (no doubling of Scr). Fifty-three percent of patients at least doubled their Scr (Groups 1 and 2), and 24% required dialysis. The degree of renal functional impairment had a dramatic impact on patient mortality rates (84%, 37%, and 17% in groups 1, 2, and 3, respectively). Jaundice (bilirubin greater than or equal to 2.0 mg/dL), weight gain (greater than or equal to 2.0 kg), amphotericin B use, and a pretransplant Scr greater than or equal to 0.7 mg/dL were independently associated with the subsequent development of dialysis-requiring ARF (P less than 0.001; relative risks, 3.0 to 7.7). Neither aminoglycoside/vancomycin/cyclosporine A use nor acute graft v host disease correlated with the development of ARF. A mismatched graft was a significant risk factor for ARF by univariate but not by multivariate analysis. Within 48 hours before doubling the Scr, 63% of group 1 patients had positive blood cultures and 39% developed hypotension. Of the 26 group 1 patients who had urine Na concentrations measured, 85% had values less than or equal to 40 mEq/L. Autopsy kidney specimens provided no clear explanation for ARF in the vast majority of patients in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗