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5 Cards in this Set
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1 Summarizetypes of bone marrow transplant and describe when they are indicated. |
· Autologous= Own cells o Advantage:Allows you to give more intense chemo for non-leukemia tumors. · Indications:Multiple myeloma (cancer of plasma cells) Amyloidosis Germcell cancers Hodgkin’s lymphoma Some leukemias§ Syngenic:Patient given cells from identical twin § Disadvantagebecause of lack of GVL effect of allogenic transplants that helps reduce tumorrelapse. Contraindicaton:Leukemia o Allogenic:Patient given§ Indications:Aplastic anemia (body stopsproducing RBCs) Myelodysplasia (poorlyformed RBCs) Myelofibrosis(extensive scar tissue in the BM) Highgrade Lymphoma Relapse of acuteleukemia |
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1 Describethe alleles considered for HLA typing and assess the importance of each inselecting a bone marrow donor. |
HLA-DR followed by -A, -B, -C. |
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Explain the complications following bone marrow transplant and methods for prevention of each following a transplant. |
Graft Versus Host Disease (GVHD) [See LO #8]Graft failure- characterized by failure to achieve appropriate of WBC count by a certain post-transplant time point (early graft failure), or spontaneous failure functioning graft (late graft failure) Graft failure due to rejection- could be the underlying cause of graft failure, Donor cells are rejected by residual host effector immune cells Detection and Consequences of graft failure:Graft failure can result in prolonged need for transfusions, need for a second transplant, and infection risk due to patient experiencing an extended period of time without WBCsDetection requires close monitoring of blood cell counts and, occasionally, bone marrow biopsyPrevention of graft failure:Prevention: Regimen of immunosuppressive drugs post-transplant (determined by current standard of care) Infection . Time to complete immune reconstitution after a bone marrow transplant > 1 year. During this time the risk of infection is quite high (see table below). Thus, patients need to be monitored closely. Organ injury Along with organ injury from GVHD, hepatic veno-occlusive disease can arise as a complication of the high-dose chemo given before the BM transplant. Lungs can also be affectedRequires supportive therapy |
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Describe the pathophysiology of acute graft-versus-host disease (GVHD) and chronic GVHD. Explain the body sites affected and potential interventions. |
Acute GvHD: <100daysMain problems = Skin, Gut, Liver Chronic GvHD: >100days Pathophysiology:Step 1: Irradiation or chemotherapy is given to patient in preparation for transplant. This damages tissues, leading to increased release of inflammatory cytokines (e.g. TNF-α, IL-1). In addition, GI tissue injury causes leakage of endotoxin (LPS) from bacteria in the gut into systemic circulation, further enhancing the inflammatory response. Step 2: Resting donor T-cells in secondary lymphoid tissue become activated via alloantigen presentation and proliferate (mainly into Th1 cells, which then secrete IL-2 and IFN-γ). Step 3: Continued release of inflammatory cytokines direct these donor effector T cells to target organs, where they mediate tissue injury and destruction. (Williams, Hematology) Clinical features:Acute: Maculopapular rash, jaundice, hepatosplenomegaly, diarrhea Chronic: skin lesions, keratoconjunctivitis, buccal mucositis (mouth), intestinal abnormalities, chronic liver disease, pulmonary insufficiency, joint contractures/debility |
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Explain the benefits of mild/moderate graft-versus-host disease in the treatment of leukemia. |
Donor-derived immune cells (namely, T cells) from the donor graft recognize and eliminate residual host tumor cells. |
