RESUMEN
Successful adoptive T cell therapy (ACT) requires the ability to activate tumor-specific T cells with the ability to traffic to the tumor site and effectively kill their target as well as persist over time. We hypothesized that ACT using marrow-infiltrating lymphocytes (MILs) in multiple myeloma (MM) could impart greater antitumor immunity in that they were obtained from the tumor microenvironment. We describe the results from the first clinical trial using MILs in MM. Twenty-five patients with either newly diagnosed or relapsed disease had their MILs harvested, activated and expanded, and subsequently infused on the third day after myeloablative therapy. Cells were obtained and adequately expanded in all patients with anti-CD3/CD28 beads plus interleukin-2, and a median of 9.5 × 10(8) MILs were infused. Factors indicative of response to MIL ACT included (i) the presence of measurable myeloma-specific activity of the ex vivo expanded product, (ii) low endogenous bone marrow T cell interferon-γ production at baseline, (iii) a CD8(+) central memory phenotype at baseline, and (iv) the generation and persistence of myeloma-specific immunity in the bone marrow at 1 year after ACT. Achieving at least a 90% reduction in disease burden significantly increased the progression-free survival (25.1 months versus 11.8 months; P = 0.01). This study demonstrates the feasibility and efficacy of MILs as a form of ACT with applicability across many hematologic malignancies and possibly solid tumors infiltrating the bone marrow.
Asunto(s)
Médula Ósea/inmunología , Inmunoterapia Adoptiva/métodos , Activación de Linfocitos , Linfocitos Infiltrantes de Tumor/trasplante , Mieloma Múltiple/terapia , Linfocitos T/trasplante , Adulto , Anciano , Baltimore , Separación Celular/métodos , Células Cultivadas , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/mortalidad , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/inmunología , Mieloma Múltiple/mortalidad , Agonistas Mieloablativos/uso terapéutico , Inducción de Remisión , Linfocitos T/inmunología , Factores de Tiempo , Resultado del Tratamiento , Microambiente TumoralRESUMEN
PURPOSE: To show that the immunomodulatory drug lenalidomide can be used in patients with relapsed multiple myeloma to augment vaccine responses. EXPERIMENTAL DESIGN: Early phase clinical trial of patients with multiple myeloma who received at least one prior therapy. Patients were treated with single-agent lenalidomide and randomized to receive two vaccinations with pneumococcal 7-valent conjugate vaccine (PCV) on different schedules. Cohort A received the first PCV vaccination prior to the initiation of lenalidomide and the second vaccination while on lenalidomide. Cohort B received both vaccinations while on lenalidomide. RESULTS: PCV-specific humoral and cellular responses were greater in cohort B than A and were more pronounced in the bone marrow than the blood, suggesting that maximal vaccine efficacy was achieved when both vaccines were administered concomitantly with lenalidomide. Patients with a clinical myeloma response showed evidence of a tumor-specific immune response with increases in myeloma-specific IFN-γ(+) T cells and reductions in Th-17 cells. CONCLUSIONS: This is the first clinical evidence showing that lenalidomide augments vaccine responses and endogenous antitumor immunity in patients and as such may serve as an adjuvant for cancer and possibly infectious vaccines.
Asunto(s)
Antineoplásicos/uso terapéutico , Inmunomodulación/efectos de los fármacos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/inmunología , Talidomida/análogos & derivados , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Vacunas contra el Cáncer/inmunología , Estudios de Cohortes , Femenino , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Vacunas Neumococicas/inmunología , Linfocitos T/inmunología , Talidomida/farmacología , Talidomida/uso terapéutico , Vacunas Conjugadas/inmunologíaRESUMEN
PURPOSE/OBJECTIVES: To describe spiritual issues addressed by users of a pancreatic cancer informational Web site. DESIGN: Qualitative, descriptive. SETTING: The patient and family chat room of Johns Hopkins Hospital's pancreatic cancer Web site. SAMPLE: 600 postings on the pancreatic cancer Web site. METHODS: Identification of categories and themes in Web postings using the constant comparison method of content analysis. MAIN RESEARCH VARIABLES: Spirituality, relationship of the person posting a message (poster) to the person with cancer. FINDINGS: Relationship of the poster to the person with pancreatic cancer was explicit in 68% (n = 410) of the 600 postings, and 83% of those 410 postings indicated that the poster was a family member. Issues of spirituality appeared in 19% (n = 114) of the 600 postings and addressed four themes: spiritual convergence, reframing suffering, hope, and acceptance of the power of God and eternal life. Six percent of postings were by family members reporting on the death of their loved ones, suggesting that the site also served a bereavement function. CONCLUSIONS: Family members of patients with pancreatic cancer sought and received spiritual comfort in a variety of forms in an Internet-based cancer chat room. IMPLICATIONS FOR NURSING: Nurse developers of cancer information Web sites should periodically assess how the sites are being used and apply the information to the refinement of the sites to better meet user needs. Further study is needed to develop and evaluate cancer Web sites as an evolving medium for providing spiritual support to family members of patients with life-threatening forms of cancer.
Asunto(s)
Familia/psicología , Internet , Neoplasias Pancreáticas/psicología , Grupos de Autoayuda , Espiritualidad , Actitud Frente a la Muerte , Costo de Enfermedad , Curación por la Fe , Femenino , Humanos , Masculino , Neoplasias Pancreáticas/complicaciones , Investigación Cualitativa , Estrés Psicológico/etiología , Estrés Psicológico/psicologíaRESUMEN
The Internet provides access to health information and a supportive community with similar illness concerns. Securing accurate information about treatment and prognosis is important to those with pancreatic cancer given its high mortality and short survival. The purpose of this descriptive-comparative study was to determine the effect of a Frequently Asked Questions (FAQ) module on postings in the chat room of a pancreatic cancer Web site. Six hundred postings were analyzed. Three themes were isolated: information seeking, giving, or both; support seeking, giving, or both; and reporting status or death. Information included treatments, nutrition, prognosis, end-of-life care, cost of care, symptoms, and support (social, emotional, spiritual, or physical). A greater proportion of postings sought information after the FAQ module was added, although questions about medical treatment decreased, whereas questions about prognosis and end-of-life care nearly doubled. There was no difference in the proportion of postings addressing support. Medical treatment was the most common treatment reported and pain was the most common symptom reported. This study supported the addition of a FAQ module to a pancreatic cancer Web site and revealed the need for information regarding pain management and care giving at the end of life.