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KEY CONCEPTS

KEY CONCEPTS

  • imageHematopoietic stem cell transplantation (HSCT) is a process that involves intravenous infusion of hematopoietic stem cells from a donor into a recipient, after the administration of chemotherapy with or without radiation. The rationale is to increase tumor cell kill by increasing the dose of myelotoxic therapies and using donor hematopoietic stem cells to “rescue” the recipient from the hematologic toxicity. Immune-mediated effects also contribute to the tumor cell kill observed after allogeneic HSCT.

  • imageHematopoietic stem cells used for transplantation can come from the recipient (autologous) or from a related or unrelated donor (allogeneic). If the related donor is a twin, the transplant is referred to as a syngeneic transplant.

  • imageHuman leukocyte antigen (HLA) mismatching of allogeneic donor-recipient pairs at either class I or class II loci increases the risk of graft failure, graft-versus-host disease (GVHD), and worsens survival. The ideal donor is one that is matched at HLA-A, B, C, and DRB1.

  • imageHematopoietic stem cells are found in the bone marrow, peripheral blood, and umbilical cord blood. Because of the rarity and similarity to other cells, hematopoietic stem cells are difficult to isolate and measure. These stem cells express the CD34 antigen, and measurement of the number of CD34+ cells is a clinically useful measure of the number of hematopoietic stem cells.

  • imageBecause of clinical and economic advantages, peripheral blood has replaced bone marrow as the source of hematopoietic stem cells in the autologous and adult allogeneic HSCT setting.

  • imageThe purpose of the preparative (or conditioning) regimen in traditional myeloablative transplants is twofold: (a) maximal tumor cell kill and (b) immunosuppression of the recipient to reduce the risk of graft rejection (allogeneic HSCT only).

  • imageReduced-intensity conditioning regimens (including those that are nonmyeloablative) have been developed in order to reduce early posttransplant morbidity and mortality while maximizing the graft-versus-malignancy (GVM) effect. The advantage of this approach is that patients who would otherwise not be eligible for allogeneic HSCT can be offered a potentially curative therapy.

  • imageTransplant-related mortality associated with allogeneic HSCT ranges from 10% to 80% depending mostly on age, recipient performance status, donor source and degree of HLA matching, and disease status. Major causes of death include relapse, infection, organ toxicity, and GVHD. The most common cause of death after autologous HSCT is disease relapse; transplant-related mortality is usually less than 5%, depending on the conditioning regimen, age, and disease status.

  • imagePatients undergoing allogeneic HSCT are given prophylactic immunosuppressive therapy, which inhibits T-cell activation, proliferation, or both. The most commonly used GVHD prophylaxis regimens are cyclosporine or tacrolimus and methotrexate. Sirolimus or mycophenolate mofetil are often substituted for methotrexate.

  • imageInitial treatment of both acute and chronic GVHD consists of prednisone, either alone or combined with cyclosporine or tacrolimus. Treatment of patients with steroid-refractory GVHD is unsatisfactory.

PRECLASS ACTIVITY

Preclass Engaged Learning Activity

Watch the “What is GVHD?” video available on the YouTube website. This video gives a brief overview ...

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