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Hematopoietic stem cell transplantation is a valuable treatment for a variety of hematologic malignancies and a few nonhematologic cancers and nonmalignant conditions. In many cases, stem cell transplantation offers the only curative option and can be a life-saving procedure. Immune effector cell (eg, T-cell, NK-cell) transplantation is an emerging approach in hematologic and solid malignancies that utilizes immune cells genetically engineered to recognize cancer-specific epitopes and incite an immune response against cancer. Autologous-derived T-cell therapies targeting CD19 are FDA approved for the treatment of aggressive lymphomas.
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AUTOLOGOUS STEM CELL TRANSPLANTATION
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The dose-limiting toxicity of almost all cancer chemotherapy has been myelosuppression from damage to the bone marrow. For cancers for which there is a dose-response relationship, that is, a relationship between the dose of chemotherapy administered and the number of cancer cells killed, the limits placed on the allowable dose of chemotherapy can make the difference between failure and cure. In autologous stem cell transplantation, the limit placed on the allowable dose of chemotherapy by the risks of permanent bone marrow damage is eliminated and much higher doses of chemotherapy can be given, since reinfusion of hematopoietic stem cells collected from the patient can completely restore the bone marrow.
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Hematopoietic stem cells were once collected from the bone marrow but are now more commonly collected from the peripheral blood after administration of stimulants such as filgrastim (G-CSF) or the CXCR4 antagonist plerixafor with or without chemotherapy. Then, during a leukapheresis, the patient's blood is centrifuged into layers of different densities and the hematopoietic stem cells are collected from the appropriate layer while the remainder of the blood elements are returned unchanged to the patient. After collection, these autologous hematopoietic stem cells are frozen and cryopreserved for later use. Autologous stem cell transplantation involves administration of high-dose chemotherapy (the "preparative regimen") followed, after clearance of the chemotherapy out of the patient's system, by intravenous reinfusion of the thawed autologous hematopoietic stem cells. The hematopoietic stem cells home to the bone marrow and form all blood components and immune cells.
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During the autologous stem cell transplantation, there is a period of severe pancytopenia between the myelosuppression caused by the chemotherapy and the recovery produced by the new bone marrow derived from the infused stem cells. This period of pancytopenia typically lasts 7–10 days and requires support with red blood cell and platelet transfusions as well as antibiotics. The morbidity of such a treatment varies according to the type of chemotherapy used, and the chance of fatal treatment-related complications is between 1% and 4%.
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Autologous stem cell transplantation is the treatment of choice for some cancers that have recurred after initial treatment but are still responsive to chemotherapy, such as lymphomas (recurrent diffuse large B-cell lymphomas and relapsed Hodgkin lymphomas) and recurrent testicular germ cell cancers. Based on the aggressive clinical course of peripheral T-cell lymphomas, autologous stem cell transplantation is often used ...