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Biomedical subjects

Robert Dean

Publications and source records attributed to Robert Dean.

6 recordsLinked to original sources
PubMed2004

Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer.

PURPOSE: Allogeneic T lymphocytes can induce regression of metastatic breast cancer through an immune-mediated graft-versus-tumor (GVT) effect in murine models. To determine if a clinical GVT effect exists against metastatic breast cancer, allogeneic lymphocytes were used as adoptive cellular therapy after a reduced-intensity chemotherapy conditioning regimen and allogeneic hematopoietic stem-cell transplantation (HSCT) from human leukocyte antigen-matched siblings. PATIENTS AND METHODS: Sixteen patients with metastatic breast cancer that had progressed after treatment with anthracyclines, taxanes, hormonal agents, and trastuzumab, received allogeneic HSCT. The reduced-intensity transplant conditioning regimen consisted of cyclophosphamide and fludarabine. To distinguish an immunological GVT effect from any antitumor effect of cytotoxic chemotherapy in the transplant-conditioning regimen, allogeneic T lymphocytes were removed from the stem-cell graft and were subsequently administered late postallogeneic HSCT. Allogeneic lymphocytes containing 1 x 10(6), 5 x 10(6), and 10 x 10(6) CD3(+) cells/kg were infused on days +42, +70, and +98 post-allogeneic HSCT, respectively. RESULTS: Objective tumor regressions occurred after day +28 post-allogeneic HSCT in six patients and were attributed to allogeneic lymphocyte infusions. Two of these responding patients had disease progression post-allogeneic HSCT before subsequent tumor regression. Tumor regressions occurred concomitantly with the establishment of complete donor T-lymphoid engraftment, were associated with the development of graft-versus-host disease (GVHD), and were abrogated by subsequent systemic immunosuppression for GVHD. CONCLUSION: Allogeneic lymphocytes can induce regression of advanced metastatic breast cancer. These results indicate that an immunological GVT effect from allogeneic lymphocytes exists against metastatic breast cancer and provide rationale for further development of allogeneic cellular therapy for this largely incurable disease.

Adoptive Transfer↗
PubMed2004

Targeted pretransplant host lymphocyte depletion prior to T-cell depleted reduced-intensity allogeneic stem cell transplantation.

Mixed chimaerism and graft rejection are higher after reduced-intensity allogeneic stem cell transplantation (RIST) with T-cell depleted (TCD) allografts. As host immune status before RIST affects engraftment, we hypothesized that targeted depletion of host lymphocytes prior to RIST would abrogate graft rejection and promote donor chimaerism. Lymphocyte-depleting chemotherapy was administered at conventional doses to subjects prior to RIST with the intent of decreasing CD4(+) counts to <0.05 x 10(9)cells/l. Subjects (n = 18) then received reduced-intensity conditioning followed by ex vivo TCD human leucocyte antigen-matched sibling allografts. All evaluable patients (n = 17) were engrafted; there were no late graft failures. At day +28 post-RIST, 12 patients showed complete donor chimaerism. Mixed chimaerism in the remaining five patients was associated with higher numbers of circulating host CD3(+) cells (P = 0.0032) after lymphocyte-depleting chemotherapy and was preferentially observed in T lymphoid rather than myeloid cells. Full donor chimaerism was achieved in all patients after planned donor lymphocyte infusions. These data reflect the importance of host immune status prior to RIST and suggest that targeted host lymphocyte depletion facilitates the engraftment of TCD allografts. Targeted lymphocyte depletion may permit an individualized approach to conditioning based on host immune status prior to RIST.

Adult↗
PubMed2003

New learning.

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Humans↗
PubMed2002

Management of the clinically negative (N0) neck.

The clinically negative (N0) neck is defined by its absence of palpable or radiographically suspicious lymph nodes. Management of patients staged N0 is controversial. Clinical studies have lacked sufficient power and follow-up time to show a survival benefit for any particular option. Current options include observation, elective neck irradiation, and elective neck dissection. Treatment plans are based on treatment of the primary tumor and surgeon preference.

Clinical Trials as Topic↗
PubMedDate not supplied

The magnetic resonance imaging profile of occult intracranial violations as a result of sinus surgery.

INTRODUCTION: Intracranial injury is a well-described complication of sinus surgery. Although such complications are typically associated with catastrophic morbidity, the neurological sequelae may be subtle and even unrecognized during the postoperative period. Magnetic resonance imaging (MRI), which can distinguish intracranial hemorrhage and injury, may provide a means for the accurate assessment of atypical presentations of occult intracranial complications. OBJECTIVE: To describe the MRI profile of occult intracranial complications that result from unrecognized skull base violation during sinus surgery. METHOD: Retrospective chart review. RESULTS: Two patients, who had endoscopic sinus surgery performed elsewhere, underwent postoperative MR for further evaluation of headache. The available medical records, as well as the patient's personal reports, suggested that no intraoperative cranial base compromise had occurred. Both MRIs showed abnormal signal intensity in the brain parenchyma adjacent to the floor of the anterior cranial fossa; these findings are consistent with traumatic injury presumably from the surgical procedure. Neither patient developed postoperative cerebrospinal fluid rhinorrhea, and neither patient experienced focal neurological deficits. CONCLUSION: New-onset and/or atypical headache after sinus surgery may be associated with occult intracranial injury. MRI may serve as the diagnostic means for this occult intracranial violation. Significant incongruity may exist between patient symptoms and the objective MR evidence that can suggest serious intracranial injury. MRI signal patterns can provide both temporal and anatomical cues about the specific injury.

Adult↗