Conversion to full donor chimerism following donor lymphocyte infusion is associated with disease response in patients with multiple myeloma.

Donor lymphocyte infusions (DLIs) have been demonstrated to induce clinical responses in patients with relapsed multiple myeloma after allogeneic bone marrow transplantation, but the immunologic mechanisms involved have not been well characterized. In patients with chronic myelocytic leukemia (CML), remissions following DLI are invariably associated with conversion to complete donor hematopoiesis, suggesting that the target antigens of this response are expressed on both normal and CML-derived hematopoietic stem cells. In the present study, we examined hematopoietic chimerism and the complexity of the T-cell receptor (TCR) repertoire in 4 patients with relapsed multiple myeloma who received infusions of donor CD4+ lymphocytes.

Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host disease in patients with relapsed multiple myeloma after donor lymphocyte infusion.

Recent reports of clinical responses following donor lymphocyte infusions (DLI) in patients with relapsed multiple myeloma (MM) after allogeneic BMT have demonstrated the ability of allogeneic cells to mediate a graft-versus-myeloma (GVM) effect, but the mechanisms involved have not been determined. To identify changes in the T cell compartment associated with DLI, we performed a molecular analysis of the T cell receptor (TCR) repertoire in four patients with relapsed MM who received infusions of CD4+ lymphocytes from HLA-identical sibling donors. Three of the four patients demonstrated a clinical anti-myeloma response following DLI but also developed graft-versus-host disease (GVHD).

Reconstitution of T-cell receptor repertoire diversity following T-cell depleted allogeneic bone marrow transplantation is related to hematopoietic chimerism.

CDR3 spectratyping was used to analyze the complexity of the T-cell repertoire and to define the mechanisms and kinetics of the reconstitution of T-cell immunity after allogeneic bone marrow transplantation (BMT). This method, which is based on polymerase chain reaction amplification of all CDR3 regions using the T-cell receptor (TCR) Vbeta genes, was used to examine serial samples of peripheral blood lymphocytes from 11 adult patients with chronic myelogenous leukemia (CML) who underwent T-cell-depleted allogeneic BMT. In contrast to 10 normal donors who display highly diverse and polyclonal spectratypes, patient samples before and early after BMT revealed markedly skewed repertoires, consisting of absent, monoclonal, or oligoclonal profiles for the majority of Vbeta subfamilies.

The BCR/ABL oncogene alters the chemotactic response to stromal-derived factor-1alpha.

The chemokine stromal-derived factor-1alpha (SDF-1alpha) is a chemoattractant for CD34(+) progenitor cells, in vitro and in vivo. The receptor for SDF-1alpha, CXCR-4, is a 7 transmembrane domain receptor, which is also a coreceptor for human immunodeficiency virus (HIV). Here we show that transformation of hematopoietic cell lines by BCR/ABL significantly impairs their response to SDF-1alpha.

Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma.

We report the results of high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) in patients with relapsed indolent follicular lymphoma. Between March 1985 and May 1995, 153 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total body irradiation and bone marrow (BM) purging. All patients received multiple chemotherapy regimens before ABMT.

Outcome in patients with myelodysplastic syndrome after autologous bone marrow transplantation for non-Hodgkin's lymphoma.

Purpose: The absolute risk of myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for non-Hodgkin's lymphoma (NHL) exceeds 5% in several reported series. We report the outcome of a large cohort of patients who developed MDS after ABMT for NHL.

Patients And Methods: Between December 1982 and December 1997, 552 patients underwent ABMT for NHL, with a uniform ablative regimen of cyclophosphamide and total body irradiation followed by reinfusion of obtained marrow purged with monoclonal antibodies.

Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion.

Purpose: Donor lymphocyte infusion (DLI) can restore complete remission in patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell-depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of salvage treatment for patients with DLI after TCD allogeneic BMT prompted an evaluation of overall outcome after CD6+ -TCD allogeneic BMT for patients treated during the time when DLI has been available.

Patients And Methods: We performed a retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic BMT for stable-phase CML and compared these outcomes with those of 40 patients who underwent non-TCD allogeneic BMT.

Efficacy and costs of granulocyte colony-stimulating factor in allogeneic T-cell depleted bone marrow transplantation.

Hematopoietic growth factors have shown clinical benefits in patients undergoing chemotherapy and stem cell transplantation, but few studies have been performed to assess whether the benefits are worth the costs. We reviewed 196 patients undergoing T-cell depleted related donor bone marrow transplantation (BMT) between 1990 and 1996 to assess the effect of growth factor use on time to engraftment and costs of hospitalization. Beginning in 1994, based on encouraging results in autologous transplantation, patients (n = 81) were treated with granulocyte colony-stimulating factor (G-CSF) starting at day +1 after marrow infusion until engraftment.

CD6+ T cell-depleted allogeneic bone marrow transplantation for non-Hodgkin's lymphoma.

For patients with non-Hodgkin's lymphoma (NHL) undergoing blood or bone marrow transplantation (BMT), the use of autologous grafts has often been preferred to that of allogeneic stem cells because of a significantly lower incidence of non-relapse mortality. If complications associated with allo-BMT could be minimized without compromising efficacy, then it might become a preferred strategy for certain subsets of patients. In this report, we describe the toxicity and long-term efficacy of T cell-depleted allogeneic BMT using anti-CD6 monoclonal antibody and complement alone to reduce the risk of GVHD and its sequelae.

Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant.

Donor lymphocyte infusions (DLI) can induce remissions in patients who have relapsed after allogeneic bone marrow transplantation (BMT). However, DLI frequently also result in significant acute and/or chronic graft-versus-host disease (GVHD). Several clinical and experimental lines of evidence have suggested that CD8(+) T cells play a critical role in the pathogenesis of GVHD.

Guillain-Barré syndrome following allogeneic bone marrow transplantation.

We describe four patients who developed Guillain-Barré syndrome (GBS) following allogeneic bone marrow transplantation (BMT). All four patients had a febrile illness before developing GBS. Two patients had mild graft-versus-host disease but did not require immunosuppression.

Characterization of T cell repertoire in patients with graft-versus-leukemia after donor lymphocyte infusion.

The clinical efficacy of donor lymphocyte infusions (DLI) in patients with relapsed chronic myelocytic leukemia after allogeneic bone marrow transplantation has been demonstrated in several recent studies. Although it is presumed that allogeneic T cells mediate this graft-versus-leukemia (GVL) effect, the influence of DLI on the T cell compartment of recipients has not been determined. To characterize the immunologic effects of DLI and to identify T cell changes selectively associated with the GVL response, we analyzed the T cell receptor (TCR) repertoire in four patients with relapsed chronic myelocytic leukemia who achieved a complete remission after infusion of CD4+ lymphocytes from HLA-identical sibling donors.

CD6-depleted allogeneic bone marrow transplantation for acute leukemia in first complete remission.

The appropriate timing of bone marrow transplantation (BMT) for adults with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) is controversial. Although allogeneic transplantation results in a lower risk of disease recurrence than intensive chemotherapy alone, overall outcome following BMT may not be improved due to the higher incidence of therapy-related fatal complications, frequently as a result of the development of graft-versus-host disease (GVHD). Selective T-cell depletion of donor marrow can reduce the incidence of GVHD and thereby limit transplant-related toxicity.

CD6+ T cell depleted allogeneic bone marrow transplantation from genotypically HLA nonidentical related donors.

The widespread use of allogeneic bone marrow transplantation (BMT) is limited by the availability of suitable donors. Recent attempts to expand the donor pool by employing HLA matched unrelated marrow have been partially successful. However, severe graft-versus-host disease (GVHD) and graft failure remain obstacles and contribute to the substantial morbidity and mortality associated with matched unrelated BMT.

Distinct patterns of minimal residual disease associated with graft-versus-host disease after allogeneic bone marrow transplantation for chronic myelogenous leukemia.

Purpose: Allogeneic bone marrow transplantation (BMT) has been shown to provide effective therapy for chronic myelogenous leukemia (CML), but previous reports have also demonstrated the persistence of bcr-abl-positive cells for months to years after BMT in the majority of patients. To evaluate the biologic significance of persistent bcr-abl-positive cells, we examined the relationship between clinical parameters known to affect the risk of relapse and the ability to detect bcr-abl-positive cells post-BMT.

Patients And Methods: We analyzed 480 samples from 92 patients at two transplant centers for the presence of bcr-abl-positive cells by polymerase chain reaction (PCR).

Immunomodulatory effects of donor lymphocyte infusions following allogeneic bone marrow transplantation.

Recently, donor lymphocyte infusions have been successfully used to treat patients with CML who have relapsed following allogeneic bone marrow transplantation (BMT). Responses can be achieved in more than 60-70% of patients with stable phase CML without the need for the additional high dose cytotoxic chemotherapy that would accompany a second transplant procedure. The clinical and molecular remissions induced by this approach are a clear demonstration of graft-versus-leukemia (GVL) activity.

Persistence of myeloid progenitor cells expressing BCR-ABL mRNA after allogeneic bone marrow transplantation for chronic myelogenous leukemia.

Previous studies have shown that tumor-specific bcr-abl mRNA can often be detected by polymerase chain reaction. (PCR) for months to years after allogeneic bone marrow transplantation (BMT) for chronic myelocytic leukemia (CML). Nevertheless, the presence of bcr-abl mRNA by itself does not invariably predict for clinical relapse post-BMT.

Reperfusion-induced arrhythmias are not prevented by ibuprofen in isolated rat heart.

Free radicals have been implicated in the genesis of reperfusion-induced arrhythmias and the cyclooxygenase pathway has been suggested as a potential source. We have therefore assessed whether a cyclooxygenase inhibitor, ibuprofen, is able to reduce reperfusion-induced injury in the isolated perfused rat heart. A duration of 10 min of regional ischemia, which resulted in a high (83%) incidence of ventricular fibrillation, was selected and hearts (n = 12/group) were perfused with ibuprofen (2, 20, or 30 mg/L) throughout the experiment.

An aggressive approach to prostatic cancer.

During the last 47 years an aggressive approach to the treatment of prostatic malignancies has been maintained at the Duke University Medical Center. Radical prostatectomy, usually by the perineal route and, more recently, by the retropubic technique in conjunction with pelvic lymphadenectomy, has been vigorously applied in patients with diffuse stages A, B and even C diseases. A 5-year survival rate of 80 per cent has been documented.