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Biomedical subjects

C Dunbar

Publications and source records attributed to C Dunbar.

At least 37 records · Page 2Linked to original sources
PubMed1996

CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies.

After autologous or allogeneic transplants of peripheral blood stem cells (PBSC), an adequate dose of CD34+ cells is necessary to ensure early and sustained hematopoietic engraftment and favorable clinical outcome. There are no comparable data on the relationship between CD34+ cell dose and recovery after allogeneic bone marrow transplants (BMT). Twenty-eight patients with hematologic malignancies received a BMT from an HLA-identical sibling, using T-cell depletion and cyclosporin for graft-versus-host disease prophylaxis and delayed donor lymphocyte transfusions in an attempt to prevent leukemia relapse. The treatment-related mortality (TRM), primarily due to infections and cytopenias, was significantly higher for 13 patients receiving less than 1 x 10(6) CD34+ cells/kg (64.9% +/- 12.8% v 6.9% +/- 6.4%, P = .003). Survival at a median follow-up of 1 year was also lower in the group receiving less than 1 x 10(6) CD34+ cells/kg (30.8% +/- 12.8 v 74.3% +/- 13.7%, P = .005). The CD34+ cell dose was the only variable significantly associated with TRM. The dose of CD34+ cells also correlated with speed of hematopoistic recovery. Patients receiving more than 2 x 10(6) CD34+ cells/kg showed significantly earlier recovery of monocytes and a trend for earlier recovery of lymphocytes. They achieved platelet and red blood cell transfusion independence earlier, required less granulocyte colony-stimulating factor support during ganciclovir treatment, and spent fewer days in the hospital after transplantation. These results suggest that, for allogeneic T-cell-depleted BMT, the higher CD34+ cell doses may improve outcome in engrafting patients.

Adult↗
PubMed1996

Retroviral mediated transfer of the cDNA for human glucocerebrosidase into hematopoietic stem cells of patients with Gaucher disease. A phase I study.

Patients with Gaucher disease suffer from a lack of functional glucocerebrosidase enzyme (Gc). Disease symptoms are a result of macrophage engorgement secondary to this enzyme deficiency. This study is designed to determine if cDNA encoding normal Gc can be introduced into macrophage precursors using a retroviral vector. CD34+ cells obtained from G-CSF mobilized peripheral blood stem cells or from bone marrow will be transduced ex vivo using one of the following three methods of transduction: 1) GlGc retroviral supernatant in the presence of autologous stroma over a period of 72 hours, 2) GlGc retroviral supernatant in the presence of interleukin-3, interleukin-6, stem cell factor and autologous stroma over a 72 hour period, 3) G1Gc retroviral supernatant in the presence of interleukin-3, interleukin-6, and stem cell factor over a 72 hour period. These transduced cells will be reinfused into the patient and the patient monitored for toxicities as well as evidence of successful gene transfer and expression. A total of twenty-four patients will be enrolled on the protocol. Patients will be assigned in equal numbers to each of six groups. The two sites participating are the National Institutes of Health and Childrens Hospital of Los Angeles.

Clinical Protocols↗
PubMed1996

Early reactivation of cytomegalovirus and high risk of interstitial pneumonitis following T-depleted BMT for adults with hematological malignancies.

Reactivation of cytomegalovirus (CMV) is a major cause of morbidity and mortality following allogeneic bone marrow transplantation (BMT) and early reactivation with increased risk of interstitial pneumonia (IP) has been reported in T cell-depleted BMT. In 21 patients at risk for CMV reactivation following T cell-depleted BMT for hematological malignancies, CMV reactivation was the main cause of transplant-related mortality: 19 (90.5%) reactivated CMV and five (26% actuarial) developed fatal IP. Median reactivation time post-BMT was 22 days for IP and 39.5 days for non-IP patients (P = 0.04). Patients developing IP showed no increase in lymphocyte count following CMV reactivation. There was a trend for higher pp65 antigen load at reactivation in patients who relapsed with CMV or progressed to IP. Donor lymphocyte transfusions (DLT) were given to pre-empt leukemic relapse and viral infection (15 patients) or to treat IP in two. Nine of 19 patients reactivated CMV before receiving DLT on day 30 post-BMT and DLT were ineffective in established IP. However DLT from seropositive donors did not cause IP. These results confirm the relationship of donor T cell function with CMV reactivation following BMT. They suggest that patients receiving T cell-depleted BMT should be protected from CMV disease with prophylactic rather than pre-emptive treatments.

Adolescent↗
PubMed1995

Growth factors and stromal support generate very efficient retroviral transduction of peripheral blood CD34+ cells from Gaucher patients.

We have achieved high-efficiency gene transfer into nonmobilized peripheral blood (PB) CD34+ cells from patients with Gaucher's disease using a clinically acceptable retroviral supernatant transduction protocol. In our studies, bone marrow (BM) and PB CD34+ cells were transduced using a high titer (10(8) particles/mL) retroviral supernatant once a day for 4 consecutive days in the presence of interleukin-3 (IL-3), IL-6, and stem cell factor (SCF), with or without an irradiated allogeneic BM stromal layer. The growth factors alone resulted in 29% +/- 10% gene transfer of PB CD34+ clonogenic cells in contrast with 71% +/- 17% gene transfer efficiency using stroma with the growth factors; a 2.5-fold increase. The increase in gene transfer efficiency was less prominent when BM CD34+ cells were used (40% +/- 16% without and 57% +/- 8% with stroma, a 1.5-fold increase). The overall transduction efficiency of both PB and BM CD34+ cells was lower when the cells were transduced over a stromal cell layer without added growth factors. The combination of IL-3, IL-6, and SCF with stroma transduced 75% of primitive long-term culture initiating cells (PB LTC-ICs) in comparison with 34% of LTC-ICs when IL-3, IL-6, and SCF were used without stromal support. Using this clinically acceptable supernatant/cytokines/stroma transduction protocol, correction of the glucocerebrosidase (GC) deficiency in the progeny cells of PBLTC-ICs from Gaucher's-disease patients has been accomplished. Efficient transduction of the PB CD34+ cells using this transduction protocol may allow repeated delivery of "GC-corrected" hematopoietic stem and progenitor cells to Gaucher's-disease patients.

Antigens, CD↗
PubMed1995

Bill Gates eyes healthcare market.

The entrepreneurial spirit is still top in Bill Gates' mind as he look toward healthcare and other growth industries. Microsoft's CEO has not intention of going the way of other large technology companies that became obsolete before they could compete today.

Commerce↗
PubMed1995

Positive selection of CD34+ hematopoietic cells using an immunoaffinity column results in T cell-depletion equivalent to elutriation.

Acute graft-vs.-host disease (GVHD) continues to present a barrier to successful allogeneic marrow transplantation. T cell-depletion may prevent severe GVHD but carries an increased risk of graft rejection and relapse posttransplant. Clinical trials have defined the number of lymphocytes associated with sustained engraftment but low risk of significant GVHD (greater than grade I or II skin only) as < or = 10(5)/kg. We examined T cell-depletion resulting from positive selection of CD34+ hematopoietic cells with a biotinylated monoclonal anti-CD34 antibody and an immunoaffinity column. Eleven patients (six myeloma and five breast cancer) underwent both peripheral blood stem cell (PBSC) collection and marrow harvest prior to autologous transplantation. One PBSC collection and one-third of each marrow underwent column separation. PBSCs were enriched for CD34+ cells from an initial mean of 1.5 to 53.3%, while marrow went from an initial mean of 2.8 to 65.4%. PBSC were depleted of CD3+ cells from an initial mean of 9.6 x 10(9) to 8.6 x 10(6). Marrow CD3+ lymphocyte content was reduced from an initial mean of 5.6 x 10(9) to 8 x 10(5). Since the column permits quantification and salvage of depleted T cells, its use should allow re-addition of T cell-aliquots associated with minimal risk for GVHD and rejection. In addition, since PBSCs were as readily depleted as marrow, allogeneic PBSC transplant may be feasible using this method.

Antigens, CD↗
PubMed1994

Los Alamos rolls out technology transfer project for radiology.

Los Alamos National Laboratory in New Mexico has targeted the healthcare sector for defense technology conversion for peace-time use. As part of that transfer, a new teleradiology repository and network may soon give pulmonary specialists a powerful new information weapon to fight tuberculosis and other lung diseases.

Colorado↗
PubMed1994

It's not the goal ... it's the journey.

His first real odyssey began 18 years ago in Alaska. The goal was Ecuador. He got as far as the Panama Canal. Traveling man John Glaser, now vice president of Information Systems at Boston's Brigham and Women's Hospital, learned long ago that the actual goal sometimes matters less than what happens along the way.

Boston↗
PubMed1993

Treatment of severe combined immunodeficiency disease (SCID) due to adenosine deaminase deficiency with CD34+ selected autologous peripheral blood cells transduced with a human ADA gene. Amendment to clinical research project, Project 90-C-195, January 10, 1992.

Significant increases in lymphocyte adenosine deaminase activity, T cell numbers and immune function have been achieved in the two children with SCID thus far treated with autologous T cells genetically-corrected by retroviral-mediated insertion of a normal ADA gene. Although the data obtained to date demonstrate that the use of ADA gene corrected peripheral T cells appears to be an effective treatment for ADA(-)SCID, it is theoretically preferable to try to develop a treatment for these children that will result in stem cell gene correction. The genetic correction of T cell progenitors with long-term immune reconstituting ability would be more desirable because repeated infusions of genetically altered cells should not be necessary and the generation of a more complete repertoire of T cell specificities might also be possible. Furthermore, the present treatment protocol involves indefinite continuation of enzyme replacement treatment with PEG-ADA. The demonstration of ADA gene expression in the progeny of transduced stem cells may simplify the decision concerning cessation of this very costly enzyme treatment (approximately $250,000/yr./patient). Recent evidence suggests that a small fraction of bone marrow or peripheral blood mononuclear cells bearing the CD34 antigen contains hematopoietic stem cells with both lymphoid and myeloid reconstituting ability. We propose in this amendment to supplement the infusion of human ADA gene-transduced autologous T cells in children with ADA(-)SCID with autologous peripheral blood CD34+ cells transduced with a second, readily distinguishable ADA vector.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗
PubMed1993

Survey shows continued strong interest in UNIX applications for healthcare.

As part of the general computer industry movement toward open systems, many are predicting UNIX will become the dominant host operating system of the late 1990s. To better understand this prediction within the healthcare setting, Computers in Healthcare surveyed our readership about their opinions of UNIX, its current use and its relative importance as an information services strategy. The upshot? CIH readers definitely want more systems on UNIX, more healthcare applications written for UNIX and more trained resource people to help them with faster installation and more useful applications.

Attitude to Computers↗
PubMed1993

Industry watch. Survey results.

The results of two recent surveys show that enthusiasm and support for reengineering information systems is slow to catch on among information professionals and top healthcare management. Caution--and even outright pessimism--remain over the speed with which a truly computer-based patient record will be implemented. Interest in open-systems solutions, however, is up sharply.

Attitude to Computers↗