Browsing by Subject "Bone Marrow Transplant"

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    Assessment on the Precision of Total Marrow Irradiation: From Clinical to Preclinical Implementation
    (2021-06) Zuro, Darren
    Total Body irradiation (TBI) has been used for many years as the preconditioning regime before bone marrow transplant. Dose escalation of TBI produced decreased relapse rates in patients with leukemia; however, treatment-related deaths increased because of organ toxicity from TBI negating any potential therapeutic gain. In 2005 a new technique called Total Marrow radiation (TMI) was founded as an alternative to TBI. TMI is a highly conformal treatment of the human skeleton structure requiring a high degree of precision and accuracy for treatment delivery. However, there are several challenges to establish and advance TMI treatment; specifically, 1) the existence of differences in treatment setup between centers which may cause differences in dose delivery and treatment accuracy. 2) the lack of a preclinical model to better understand the biological differences between TMI and TBI. Lack of preclinical TMI model, limits us for in depth understanding of how TMI dose escalation and bone marrow microenvironment plays role in leukemia relapse and whether new therapeutics (e.g. TMI and immune modulation) could be developed to improve treatment outcomes. In this thesis, I assessed the state of current clinical TMI pre-treatment setup and its effect on dose delivery. Patient setup techniques differed between centers, creating variations in dose delivery. Image fusion accuracy varied by anatomical regions and by imaging technique. This effort allowed us to standardize treatment setup which can be used as reference for all centers. After creating a multi-center reference for TMI dose distribution, we developed and validated image guided preclinical TMI treatment technique in mice. Dose reduction in preclinical TMI mirrored that in clinical TMI.TMI treated mice showed full long-term donor engraftment after primary bone marrow transplant (BMT) and second serial BMT. Engraftment was similar to TBI. TBI-treated mice showed acute gut damage, which was minimized in mice treated with TMI. MVCT imaging and whole-body patient immobilization was essential for assessing treatment setup, allowing for the complete analysis of 3D dose distribution in the PTV and lungs. The development of a new 3D targeted preclinical system paves the way for new exploratory studies in the field of bone marrow transplant and radiobiology.
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    Effects of Hope-Based Music Therapy on Hope and Pain in Hospitalized Patients on Blood and Marrow Transplant Unit: A Convergent Parallel Mixed-Methods Pilot Study
    (2016-09) Verstegen, Amanda
    Background: Among continuous improvements in treating cancer as a physical malady, there has been an increased focus on the psychological health of cancer patients. Patients undergoing Blood and Marrow Transplantation (BMT) are particularly susceptible to the deterioration of psychological health due to the demanding nature of BMT procedures. Hope is a multidimensional construct that can impact a patient’s psychological well-being. Extant research on hope with cancer patients has promoted psychological interventions to foster and maintain hope, but has been conducted almost exclusively within the field of oncology nursing. Although researchers have identified that music therapy can be effective in the treatment and psychological care of BMT patients, to date there has been no music therapy literature with a specific focus on hope in the psychological care and support of cancer patients. Objective: The purpose of this convergent parallel mixed-methods pilot study was to target hope by adapting an existing hope intervention to music therapy treatment with patients on a BMT unit. Methods: Patients (N = 10) were randomly assigned to experimental or wait-list control conditions and all patients completed the Herth Hope Index supplemented with an 11-point Likert-Type Pain Scale at pre- and posttest. Experimental participants engaged in a two-session individualized music therapy treatment consisting of patient-preferred live music chosen from a hope-based song menu coupled with therapeutic dialogue that was adapted from the Hope Intervention Program. Experimental participants also participated in an individual semi-structured interview in an attempt to understand their experiences and perceptions of how music therapy may affect hope. The six steps of thematic analysis, as identified by Braun and Clarke (2006), were used to analyze qualitative data. Results: There was no significant between-group difference at pretest. Posttest analyses utilizing Mann-Whitney U tests revealed significant between-group differences in measures of hope with patients in experimental condition demonstrating higher hope. Although not statistically significant, there was a slight tendency for a decrease in pre- to posttest pain for the experimental condition but not for the control condition. Qualitative analyses resulted in three emerging themes: 1. Hope-based music therapy provides opportunities for positive experiences including comfort and interpersonal connection; 2. Hope-based music therapy facilitates personal depth though self-awareness and self-identity; and 3. Hope-based music therapy provides a platform to discuss and confront hope including motivations for and obstacles to hope. Conclusion: Although generalization is limited by a small sample, quantitative results supported hope-based music therapy as an effective intervention with BMT patients in this pilot study. Qualitative data reinforced and provided depth to quantitative results, revealing that hope-based music therapy elicited positive experiences, comfort, and interpersonal connection; acted as a platform to discuss hope; and supported self-awareness and self-identity. Study limitations, implications for clinical practice, and suggestions for future research are provided.
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    Indoleamine 2,3-dioxygenase: a potent regulator of graft versus host disease with potential therapeutic applications.
    (2009-06) Jasperson, Lisa Kristine
    Hematopoietic stem cell transplant is the only curative therapy for a variety of malignant and non-malignant hematologic disorders and has the potential to treat a variety of other difficult diseases. Unfortunately, the procedure carries a high risk of graft versus host disease (GVHD), limiting its efficacy and wider application. GVHD occurs when antigen disparity between donor and host leads donor T cells to become activated and proliferate. They then migrate to the liver, skin, lung, and gut and mediate tissue damage. By uncovering the positive and negative regulatory pathways in GVHD biology, new therapeutic targets can be identified. Data presented here establishes indoleamine 2,3-dioxygenase (IDO), an immunosuppressive enzyme in the tryptophan metabolism pathway, as a major regulator of GVHD. IDO-deficient recipients of bone marrow transplant suffered accelerated GVHD lethality, with pathology concentrated in the colon. IFN-γ produced by donor T cells highly upregulated colon IDO; in its absence, donor T cells underwent more proliferation and less apoptosis, leading to increased disease severity and lethality. Tryptophan depletion was not central to these effects, as T cells lacking the sensor for tryptophan were suppressed by IDO. Accordingly, treatment of transplant recipients with kynurenines, the downstream metabolites of tryptophan breakdown, ameliorated disease. IDO expressed by antigen presenting cells (APCs) was responsible for its T cell suppressive effects. By targeting APCs using a TLR agonist, IDO could be upregulated in the colon before transplantation, and this upregulation was sufficient to diminish GVHD. This work identifies IDO as a potent modulator of GVHD. This finding is then used to develop two clinically relevant therapeutic strategies for GVHD treatment and prevention.