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http://projects.csail.mit.edu/courseware/?term=psychology-reflection-essay psychology reflection essay Most patients diagnosed with cancer are elderly. Therefore, myeloablative hsct could not be offered to a substantial portion of cancer patients. The concept of donor immune response having a graftversus-tumor effect gave rise to the theory that a strongly immunosuppressive, but not myeloablative, preparative regimen (ie, a nonmyeloablative transplant may result in a state of chimerism in which the recipient and donor are coexisting). The toxicity and efficacy of nonmyeloablative transplants are being evaluated table 98–2  commonly used preparative regimens for hscta type of hsct preparative regimen dose and schedule for adults allogeneic13 myeloablative cy-tbi allogeneic, autologous14 myeloablative bu-cy   autologous15         myeloablative beam (carmustine/ etoposide/-cytarabine/ melphalan)       nonmyeloablative bu-flu cy 60 mg/kg/day iv on 2 consecutive days before tbi 1000–1575 rads (10–15. 75 gy) fractionated over 1–7 days bu 1 mg/kg per dose po or 0. 8 mg/kg per dose iv every 6 hours × 16 doses cy 60 mg/kg/day iv daily × 2 days after bu allogeneic16 carmustine 300 mg/m2 iv etoposide 400–800 mg/m2 iv given over 4 days cytarabine 400–1600 mg/m2 iv given over 4 days melphalan 140 mg/m2 iv fludarabine 30 mg/m2/day iv on day –10 to day –5 followed by busulfan 1 mg/kg/dose po every 6 hours × 8 doses on days –6 and –5 dose and schedule for pediatric patients cy 60 mg/kg/day iv on 2 consecutive days before tbi 1000–1575 rads (10–15. 75 gy) fractionated over 1–7 days bu 1 mg/kg per dose po or 0. 8 mg/kg per dose iv every 6 hours × 16 doses cy 120–200 mg/kg iv given over 2–4 days after bu   carmustine 300 mg/m2 iv etoposide 400–800 mg/m2 iv given over 4 days cytarabine 400–1600 mg/m2 iv given over 4 days melphalan 140 mg/m2 iv fludarabine 30 mg/m2/day iv on day –10 to day –5 followed by busulfan 1 mg/kg/dose po every 6 hours × 8 doses on days –6 and –5 beam, carmustine, etoposide, cytarabine, and melphalan. Bu-cy, busulfan and cyclophosphamide. Bu-flu, busulfan and fludarabine. Cy-tbi, cyclophosphamide–total-body irradiation. Iv, intravenous. Po, oral. Tbi, total-body irradiation. A 1450  section 16  |  oncologic disorders in patients with malignant and nonmalignant conditions who are not eligible for a myeloablative hsct. A nonmyeloablative preparative regimen allows for development of mixed chimerism (defined as 5%–95% peripheral donor t cells) between the host and recipient to allow for a graftversus-tumor effect as the primary form of therapy (figure 98–1). Chimerism is assessed within peripheral blood t cells and granulocytes and bone marrow using conventional (eg, using sex chromosomes for opposite-sex donors) and molecular (eg, variable number of tandem repeats) methods for same-sex donors. The nonmyeloablative preparative regimen does not completely eliminate host normal and malignant cells. Donor cells eradicate residual host hematopoiesis, and the graft-versus-tumor effects generally occur after the development of full donor t-cell chimerism. After engraftment, mixed chimerism should be present and is shown by the presence of both donor- and recipientderived cells. Autologous recovery should occur promptly if the graft is rejected. The intensity of immunosuppression required for engraftment depends on the immunocompetence of the recipient and the histocompatibility and composition of the hsct. 18 more intensive conditioning regimens that are required for engraftment in the setting of unrelated-donor- or hlamismatched-related hsct have been termed reduced-intensity myeloablative transplants. After chimerism develops, donorlymphocyte infusion can be administered safely in patients without gvhd to eradicate malignant cells. Nonmyeloablative preparative regimens typically consist of a purine analog (eg, fludarabine) in combination with an alkylating agent or low-dose tbi. Adverse effects in the early posttransplant period are decreased because of the lower intensity preparative regimen, thus making hsct available to patients preparative regimen d d who in the past were not healthy or young enough to receive a myeloablative preparative regimen. The risk of gvhd remains with nonmyeloablative transplant.

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