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BASIC CONCEPTS

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High-dose chemotherapy (HDC) with autologous hematopoietic progenitor cell (HPC) transplant is an effective treatment modality for several hematologic malignancies and selected solid tumors. This chapter reviews its current role in the treatment of cancer and outlines promising future directions of progress.

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High-dose radiation and chemotherapy are limited by toxicity to normal tissues, particularly the bone marrow. The doses of certain chemotherapeutic agents and radiation can be substantially escalated, with the goal of exploiting their dose-response effect, when followed by autologous or allogeneic transplantation of HPCs to restore hematopoiesis. Pluripotent HPC progenitors present in the graft proliferate and differentiate into the mature blood and immune cells. Autologous transplantation involves collection, cryopreservation, and infusion of the patient’s own HPCs.

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GENERAL PROCEDURES FOR AUTOLOGOUS TRANSPLANTATION

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Preceding Conventional Dose Chemotherapy

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Standard chemotherapy is usually given to reduce the tumor burden prior to proceeding with HPC transplantation (Fig. 12-1). In general, the best outcomes are noted in patients with chemosensitive disease, in complete remission (CR), or with minimal tumor burden at time of transplantation.

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FIGURE 12-1

Autologous hematopoietic progenitor cell transplantation process.

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Stem Cell Collection

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Bone marrow is collected via multiple aspirations from the posterior-superior iliac crest in a sterile environment (usually a surgical operating room) while the patient is under anesthesia. Ideally, HPCs should be collected while the patient’s marrow is normocellular and uninvolved by the malignancy. Currently, bone marrow HPC collection is rarely, if ever, done for the purpose of autologous transplantation because HPCs can be collected from peripheral blood and engraft more rapidly when collected this way. Hematopoietic progenitor cells are normally infrequent in the blood but are mobilized into the blood during the recovery after chemotherapy and following treatment with granulocyte colony-stimulating factor (G-CSF). Peripheral blood progenitor cells (PBPCs) are collected using apheresis with continuous-flow cell separation. One to four daily apheresis sessions are usually required to achieve the minimal target CD34+ cell dose (at least 2 × 106/kg). The collected PBPCs are subsequently cryopreserved and stored.

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Multiple factors have been shown to predict poor success in mobilization and collection, including advanced age; amount of preceding chemotherapy; presence of marrow-infiltrating disease; history of pelvic radiation; prior exposure to certain drugs (melphalan, carmustine, bendamustine); low premobilization platelet counts; short intervals from last chemotherapy cycle to mobilization; inadequate chemotherapy-mobilizing regimens or low-dose G-CSF (1); and previous treatment with four or more cycles of lenalidomide (2). Peripheral blood CD34+ cells more than 10/μL are usually necessary for an adequate collection. Plerixafor has become available as a second PBPC-mobilizing agent, effective for “poor mobilizers,” acting synergistically with G-CSF (3).

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High-Dose Therapy

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Autologous transplants are most effective in ...

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