A 56-year-old, previously healthy man has worsening fatigue and recurrent epistaxis. Evaluation shows anemia, thrombocytopenia, and abnormal circulating leukocytes. Bone marrow biopsy establishes a diagnosis of acute myeloid leukemia. The patient is initially treated with induction chemotherapy, and an allogeneic hematopoietic stem cell transplant is recommended. A nonrelated, HLA-matched donor is not found, so the patient's adult son volunteers to be the donor. The plan is for the patient to receive conditioning chemotherapy and radiotherapy followed by bone marrow transplant. Prior to transplant, a procedure is performed to deplete CD3⁺ cells in the marrow graft. This pretransplant procedure would be most helpful in decreasing this patient's risk for which of the following?

Question

Quizplus · Accepted Answer

11ec160b_3aef_ad59_9249_db17be448ed7_MD0001_00 Allogeneic stem cell transplantation is used in the treatment of leukemia to provide a new source of hematopoietic stem cells (HSCs) after destruction of the patient's immune cells (including malignant cells) with chemoradiotherapy. The donor's HSCs are frequently obtained from bone marrow or peripheral blood and contain differentiated immune cells such as CD3⁺ T cells. These donor CD3⁺ (CD4⁺/CD8⁺) T cells can recognize human leukocyte antigen (HLA)-mismatched host cells (including residual leukemia cells) as foreign, providing a beneficial graft versus leukemia/tumor effect. However, they can also attack normal host cells and initiate graft versus host disease (GVHD), a widespread inflammatory response that characteristically damages the skin (eg, maculopapular rash), gastrointestinal tract (eg, diarrhea, abdominal pain), and liver (eg, elevated serum bilirubin). Depletion of donor CD3⁺ T cells prior to HSC transplant is performed primarily to decrease GVHD risk, but it also has the following undesirable effects on the host: Decreased graft versus leukemia effect, increasing the risk of leukemia relapse (Choice D). Depletion of memory T cells, which increases the risk of viral (eg, cytomegalovirus, human herpes virus 6) infections (Choice A). This also increases the risk of posttransplant lymphoproliferative disease due to the reduction in donor T cells that normally attack proliferating B cells infected with Epstein-Barr virus (Choice E). (Choice C) Immunoglobulin deficiency is a normal effect of myeloablative chemoradiotherapy that improves over time with engraftment (proliferation and differentiation) of donor HSCs. Removal of donor T cells before the transplant would increase the period of B cell and immunoglobulin deficiency by slowing engraftment and reestablishment of host immune function. Educational objective: Allogeneic hematopoietic stem cell grafts normally include donor CD3⁺ T cells that can initiate graft versus host disease (GVHD), a widespread inflammatory response that can damage multiple organs. Depletion of donor CD3⁺ T cells prior to transplant decreases the risk of GVHD but also decreases the beneficial graft versus tumor effect, increasing the likelihood of cancer relapse.

A 56-Year-Old, Previously Healthy Man Has Worsening Fatigue and Recurrent