Biomedical subjects

Lawrence S Lamb

Publications and source records attributed to Lawrence S Lamb.

6 recordsLinked to original sources

PubMed2005

Characterization of the gammadelta T cell response to acute leukemia.

BACKGROUND: Previous work from our center has suggested a correlation between increased donor-derived Vdelta1+ gammadelta T cells and long-term relapse-free survival following bone marrow transplantation for leukemia. Questions remain, however, as to whether this observation can be explained by a gammadelta T cell-based immune response against primary leukemia. METHODS: We examined gammadelta T cell receptor (TCR) phenotype, cell proliferation, and cytolytic activity following culture with irradiated primary leukemia blasts from a haploidentical first-degree relative. Subsequently, we also studied the gammadelta TCR phenotype and complimentarity determining region 3 (CDR3) cDNA sequences from 17 newly diagnosed leukemia patients. RESULTS: In 17/28 (61%) of in vitro cultures, gammadelta T cells proliferated in culture with primary blasts. Vdelta1+ T cells were proportionally increased in all cultures and were the predominant cell population in 6/17. In the 7 cultures where cytotoxicity could be assessed, 6 (86%) showed some degree of cytotoxicity to the primary leukemia. Vdelta1+ T cells were also the predominant gammadelta T cell subtype in pre-treatment leukemia patients principally due to loss of Vdelta2+ T cells rather than expansion of Vdelta1+ cells. The Vdelta1 CDR3-region cDNA sequence from these patients revealed exclusive use of the Jdelta1 constant region and sequence conservation in 4/11 patients. CONCLUSIONS: gammadelta T cells exhibit an in vitro response to primary leukemia blasts that is manifested by proliferation, an increased proportion of Vdelta1+ T cells, and cytotoxicity to the primary leukemia blasts. The Vdelta1+ T cell population is also predominant in newly diagnosed leukemia patients likely due to a loss of circulating Vdelta2+ T cells. A small proportion of newly diagnosed patients showed Vdelta1 CDR3 region similarity. These findings suggest a role for gammadelta T cells in the immune response to leukemia.

Base Sequence↗

PubMed2005

T-cell lymphoblastic leukemia/lymphoma syndrome with eosinophilia and acute myeloid leukemia.

This case represents an example of an unusual T-cell lymphoblastic leukemia/lymphoma syndrome associated with eosinophilia and myeloid malignancy in a young boy. This case is one of only five reported "leukemic" variants of the disease and demonstrates the importance of considering this poor prognostic diagnosis in pediatric acute lymphoblastic leukemia. This case also illustrates the importance of an interactive multidisciplinary approach to the laboratory evaluation of a leukemia patient.

Antigens, Surface↗

PubMed2005

Hematologic aspects of myeloablative therapy and bone marrow transplantation.

The transplantation of bone marrow cells or isolated hematopoietic stem cells from the bone marrow or peripheral blood is a widely utilized form of therapy for patients with incurable diseases of the hematopoietic and immune systems. Successful engraftment of the transplanted stem cells in an adequately prepared recipient normally leads to bone marrow reconstitution over a period of several weeks, accompanied by more gradual reconstitution of the immune system. Since the recipient is profoundly ill during the initial treatment period, laboratory data is critical for monitoring engraftment, detecting residual/recurrent disease, and identifying problems that may delay bone marrow reconstitution or lead to other medical complications. Accurate blood cell counts are imperative, and most bone marrow transplantation patients undergo periodic monitoring with bone marrow aspirates and biopsies with cytogenetic, molecular, and multiparametric flow cytometric studies. The potential complications of bone marrow transplantation include engraftment failure and delayed engraftment, infection, residual bone marrow disease, acute and chronic graft versus host disease, myelofibrosis, therapy-related acute leukemia, post-transplant lympho-proliferative disorders, and toxic myelopathy.

Bone Marrow Transplantation↗

PubMed2005

gammadelta T cells: a new frontier for immunotherapy?

The use of cytolytic effector cells as therapy for malignant disease has been a central focus of basic and clinical research for nearly 2 decades. Since the original descriptions of in vitro lymphocyte-mediated cytotoxicity against human tumor cells, there have been numerous attempts to exploit such observations for therapeutic use, with decidedly mixed results. Most studies have focused on the role of either natural killer cells or cytotoxic CD8 + alphabeta T cells as the primary mediators of antitumor cytotoxicity, and until recently little attention has been paid to the role of gammadelta T cells in this capacity. This is partially due to a lack of understanding of the mechanisms of gammadelta T-cell immune responses to tumors, as well as the practical problem of obtaining a sufficient number of gammadelta T cells for clinical-scale administration. In this article, we discuss the biological and clinical rationale for developing gammadelta T cell-based immunotherapies for the treatment of a variety of malignant conditions. It is our view that infusing supraphysiological numbers of tumor-reactive gammadelta T cells-either in the autologous or allogeneic setting-might be used to restore or augment innate immune responses against malignancies. Accordingly, we will also discuss how we and others are working to overcome some of the practical limitations that have so far limited the direct clinical delivery of highly purified human gammadelta T cells for the treatment of both hematologic and solid tumors.

Hematopoietic Stem Cell Transplantation↗

PubMed2003

Efficacy of therapeutic group by telephone for women with breast cancer.

A pilot study was conducted to test the efficacy of a therapeutic group by telephone conference call for women with breast cancer. Sixty-six women with stage I or stage II breast cancer consented to participate in the study. Participants were randomly assigned to a usual psychosocial care or intervention group, using a permuted block method. Only 2 of 68 patients dropped out of the study, which included 27% African Americans. Assessments at 3 time periods (pretest, immediately after the intervention, and 3 months after the group ended) included evaluation of quality of life (QOL), mood, and immune function. ttests were performed to determine if differences on important variables existed at pretest. The intervention group had worse QOL and mood scores than did the control group on the pretests. A mixed-model repeated-measures procedure controlling for pretest differences was used to analyze data. A significant Group by Time interaction was found for spiritual well-being and mood. These differences were not in the expected direction. The intervention group showed improvement in QOL and mood during the intervention, but showed decompensation following the intervention. Conversely, the control group demonstrated stable or declining scores. This intervention is feasible and practical for women with breast cancer, especially African American participants. The puzzling results suggest several areas for future research, including a better conceptual fit with outcome measures, increasing dosage, and exploration of the value of emotional expression.

Affect↗

PubMed2002

Hematopoietic cellular therapy: implications for the flow cytometry laboratory.

Advances in hematopoietic stem cell transplantation, gene therapy, and immunotherapy have necessitated a host of novel monitoring procedures. Cell sorting is also coming of age as a clinical procedure designed to organize hematopoietic grafts for specificity of cellular components designed for individual patients or diseases. This article has focused on these novel developments in their historical context. The next generation of transplantation flow cytometry promises to be an exciting one.

Animals↗