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Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Autologous Bone Marrow Transplantation (ABMT) provides a way to rescue the hematopoietic system in patients receiving high dose chemotherapy. Solid tumors like lung and breast cancer are the targets for new therapies that involve high dose chemotherapy with AMBT due to their growth and pathologic characteristics. Reinfusion of bone marrow with metastatic neoplastic cells could also seed viable tumor cells, and thus be a reason for treatment failure, restricting high-dose chemotherapy with bone marrow support to patients whose marrow is morphologically free of tumor cells. The use magnetic beads for physical separation of tumor from normal cells and the use of a toxin delivered by a monoclonal antibody are examined as two purging methods for treatment. The use of magnetic beads conjugated with specific antibodies (SM1, LAM2 and LS1) against tumor antigens to purge 2-3 logs of Small Cell Lung Cancer (SCLC) contamination from bone marrow is demonstrated. Optimal performance calls for short double exposure to anti-tumor cell-antigen monoclonal antibodies, followed by exposure to magnetic beads coated with antibodies specific for the monoclonal anti-SCLC antibodies, maintaining a bead-to-cell ratio of 10:1 to 100:1. Specific toxin delivery to three breast cancer cell lines (ZR-75, BT20 and MCF7) expressing the DF3 antigen was demonstrated by the use of DF3 immunotoxin (DF3-IT). The optimal concentration of the DF3-IT immunotoxin for highest tumor kill was shown to be 1x1Q-9 M, but this caused a loss of bone marrow progenitor cell colonies of about 30%. Both methods are limited chiefly by the level of antigen expression in the target tumor cells. The purging efficiency could be improved by targeting a wider range of antigens or by inducing higher levels of antigen expression. From the clinical perspective, the advantages and need for purging involved bone marrow to bring about substantially improved curative strategies remains a question still unanswered. / 2031-01-01

Class of 2004 Abstract / Objective: To develop and populate a decision-analytic model comparing the cost and efficacy of imatinib versus allogenic bone marrow transplantation (BMT) with a matched unrelated donor in the treatment of newly-diagnosed, Philadelphia positive (Ph (+)), chronic phase, chronic myelogenous leukemia (CML). Design: Markov cohort analysis and Monte Carlo microsimulation. Measurements and Main Results: Direct medical costs were measured from the perspective of a third-party payer. Efficacy data and probabilities were obtained from survivability findings emanating primarily from randomized controlled trials (RCTs). A two-year time horizon was employed with three month treatment cycles. BMT was established as the baseline comparator and the base case was defined as a 35 year old, Ph(+) male patient with newly-diagnosed CML. Results from the Monte Carlo trial found that the incremental cost-efficacy ratio was −$5,000 for imatinib (95th % Confidence Interval: −$70,000, $84,000). Analysis of the cost-efficacy plane indicated that imatinib dominated BMT in 84.69 percent of cases, while BMT was dominant in 0.76 percent of cases. Sensitivity analyses of costs and discount rates found results to be robust. Conclusion: Imatinib was observed in a majority of cases to be both less costly and more efficacious relative to BMT in the treatment of CML, suggesting that this pharmaceutical agent is a dominant therapeutic strategy. When available, the incorporation of long-term clinical data are required to assess cost-efficacy beyond the two-year time horizon of this study.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Bone marrow transplants (BMT, also hematopoietic stem cell transplants or HSCT/SCT) are one of the greatest medical achievements of the 20th century. They offer a treatment for a host of malignant and nonmalignant hematopoietic disorders, genetic diseases and solid tumors that could otherwise be fatal. Studies have found that 60% of patients undergoing BMT develop pulmonary complications (PC), and 1/3 of those require intensive care after transplantation. Despite the potential pneumotoxicity of induction agents, to date there have been no longitudinal studies following pulmonary function in this high‐risk patient population. This study reviewed patient who underwent autogeneic bone marrow transplant for multiple myeloma at Banner University Medical Center – Tucson (formerly University of Arizona Health Network) from January 1, 2003 through December 31, 2013. Pretransplant evaluatin and pulmonary function testing data were obtained and stratified between high dose (standard) Melphalan (200 mg/ms2) and reduced dose (140 mg/ms2). Statistically significant differences were present between the 2 groups at baseline for DLCO but disappeared at 6 and 12‐month followup, while a statistically significant difference for FEV1/FVC ratio was seen at baseline and 6 months but disappeared at 12‐month follow‐up. There were no statistically significant differences seen with FEV1 between the two groups. Given there is no difference in mortality and relapse outcomes between the groups, the standard of care dosing for Melphalan is not associated with an increase in pulmonary morbidity.