Kessinger, A. (Anne)
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- Oligonucleotides complementary to c-myb messenger RNA inhibit growth and induce apoptosis in human Burkitt lymphoma cells(Spandidos Publications, 1996) Bishop, M.R. (Michael R.); Iversen, P. L. (Patrick L.); Graham-Sharp, J. (J.); Martin-Algarra, S. (Salvador); Kessinger, A. (Anne); Verbik, D.J. (David J.); Jackson, J.D. (John D.); Wu, AI.G. (AI G.); Joshi, S.S. (Shantaram S.); Pirruccello, S.J. (Samuel J.)A 24-mer (antisense) phosphorothioate oligonucleotide (ODN) corresponding to the codons 2-9 of the c-myb gene was evaluated for its effects on the growth of a human Burkitt lymphoma cell line (Raji) in vitro. Raji cells incubated with different concentrations of c-myb antisense ODN (5-15 M-g/ml) for 24-72 h showed a significant dosedependent decrease in growth. The same concentrations of control (sense) or scrambled c-myb phosphorothioate ODNs did not inhibit Raji cell growth. The c-myb antisense ODN, but not the control ODNs, significantly decreased c-myb mRNA levels in treated cells as determined by RT-PCR. Additionally, the c-myb antisense ODN induced apoptosis of Raji cells as demonstrated by i) flow cytometry to enumerate the A0 (apoptotic cell population) population of propidium iodide stained cells; ii) electron microscopy to evaluate the cell morphology; and iii) DNA fragmentation pattern. Thus, an antisense c-myb ODN causes significant growth inhibition of Burkitt lymphoma cells, and one mechanism of growth inhibition is the induction of apoptosis of the lymphoma cells. In addition, antisense c-myb ODN did not reduce CFUGM or BFU-e colony-forming ability of normal hematopoietic stem/progenitor cells. Because the inhibition is sequence-specific and Burkitt lymphoma cell selective, evaluation of the therapeutic effects of c-myb antisense ODN against Burkitt lymphoma is warranted.
- Hematopoietic growth factors after HLA-identical allogeneic bone marrow transplantation in patients treated with methotrexate-containing graft-vs.-host disease prophylaxis(e, 1995) Bishop, M.R. (Michael R.); Tarantolo, S. (Stefano); Martin-Algarra, S. (Salvador); Kessinger, A. (Anne); Anderson, J.R. (James R.); Armitage, J.O. (James O.); Vose, J. (Julie); Bierman, P.J. (Philip J.); Cowles, M.K. (Mary K.); Reed, E.C. (Elizabeth C.)The use of hematopoietic growth factors (HGFs) in the allogeneic transplant setting has sometimes been avoided for fear of stimulating leukemic cell growth and intensifying graft-vs.- host disease (GVHD). However, neither an increase in relapse rate nor an aggravation of GVHD has been routinely described when HGFs are used after allogeneic bone marrow transplantation (allo-BMT). Early outcomes after HLAmatched allo-BMT in 26 patients with hematologic malignancies treated with recombinant human granulocyte colonystimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGMCSF) from the day of transplantation were analyzed. Results were compared to those from a series of 38 patients treated earlier with an identical approach, but not scheduled to receive HGFs after transplantation. All patients received a preparative regimen consisting of etoposide, cyclophosphamide, and total-body irradiation and GVHD prophylaxis with cyclosporine and a short course of methotrexate (MTX). The analysis has shown that the duration of neutropenia was significantly decreased in the group of patients treated routinely with HGFs (median 17 vs. 20 days; p < 0.001). These patients also required fewer days of intravenous antibiotic therapy (median 20 vs. 34 days; p < 0.001), had fewer positive blood and tissue cultures (median 2 vs. 12 and 13 vs. 28; p = 0.02 and p = 0.05, respectively), needed fewer packed red blood cell transfusions (median 7 vs. 11; p < 0.03), and were discharged earlier from the hospital (median 33.5 vs. 39 days; p < 0.001). The use of HGFs was not associated with an increase in acute GVHD or early leukemic relapse. No side effects were attributable to the simultaneous administration of MTX and HGF during the neutropenic period. A trend toward better 100-day actuarial survival for patients treated with rhG-CSF or rhGM-CSF did not reach statistical significance. A decrease in the number of early deaths from fungal or bacterial infections was found in the cytokine-treated group (p = 0.05). These data suggest that the early use of rhGCSF or rhGM-CSF after HLA-matched allo-BMT in hematologic malignancies accelerates engraftment, reduces hospitalization time, and improves outcome, without increasing acute GVHD or early relapse. Because MTX-based prophylaxis regimens are associated with prolonged neutropenia, the routine use of HGFs after transplantation may be particularly useful in regimens including MTX.
- Hematopoietic Recovery After Allogeneic Blood Stem-Cell Transplantation Compared With Bone Marrow Transplantation in Patients With Hematologic Malignancies(American Society of Clinical Oncology, 1997) Gross, T.G. (Thomas G.); Bishop, M.R. (Michael R.); Tarantolo, S. (Stefano); Martin-Algarra, S. (Salvador); Kessinger, A. (Anne); Jackson, J.D. (John D.); Nasrati, K. (Khalliq); Armitage, J.O. (James O.); Bierman, P.J. (Philip J.); Reed, E.C. (Elizabeth C.); Kollath, J. (Jeff); Pavletic, Z.S. (Z. Steven); Vase, J.M. (Julie M.)Purpose To compare hematopoietic recovery, duration of hospitalization, and 100-day survival in patients who received allogeneic-blood stem cells (BSC) or conventional allogeneic bone marrow transplantation (BMT). Patients and Methods From December 1994 to August 1995, 21 patients participated in a phase II study of allogeneic BSC transplantation. Cells mobilized with granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg/ d) were collected from human leukocyte antigen (HLA)-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. G-CSF (10 micrograms/kg/d) was administered posttransplant. The outcomes were compared with 22 identically treated historical patients who received allogeneic BMT. Results The median infused CD34+ cell and granulocyte-macrophage colony-forming unit (CFU-GM) content were 7.73 x 10(4)/kg and 41.6 x 10(4)/kg, respectively. The median time to a neutrophil count greater than 500/ microL was 11 days after BSC and 16.5 days after BMT (P = .0003). A trend toward faster platelet and RBC recovery after BSC was observed. BSC patients received fewer platelet transfusions: 10 versus 19 (P = .015). The median length of hospitalization was shorter after BSC transplantation: 25 versus 31.5 days (P = .0243). The 100-day survival rates were similar: 83% after BSC and 75% after BMT (P = .3585). The incidence of acute GVHD grade II to IV was 57% and 45% for BSC and BMT, respectively (P = .4654). Conclusion In comparison to BMT, allogeneic BSC transplantation may result in faster hematopoietic recovery, shorter hospital stay, and similar early survival. Whether allogeneic BSC are superior to bone marrow needs to be determined in randomized trials.