Richard French, 53 years old, was diagnosed with chronic myelogenous leukemia. His elder brother Don is HLA-haploidentical and will donate bone marrow

Question

Richard's oncologist has recommended him to a medical center that favors using bone marrow depleted of mature T cells prior to infusion. The most likely rationale for employing the practice of T-cell depletion is that _____.
a. T-cell depletion will remove alloreactive T cells from the donor and prevent the potential for graft-versus-host disease (GVHD)
b. mature T-cell chimerism is required to establish long-term tolerance
c. because Don is HLA-haploidentical and male, there is no risk of alloreactivity toward major or minor histocompatibility antigens
d. because of Don's age, the expected bone marrow harvest is already marginal for successful engraftment, and depletion measures would compromise the yield of stem cells
e. the benefit of using a cocktail of immunosuppressive drugs outweighs the risk of contaminating the bone marrow during T-cell depletion.

Answer 1

Rationale: The correct answer is a. An HLA haploidentical donor has one HLA haplotype in common with the recipient and one that is different. A bone marrow sample from a haploidentical donor contains numerous alloreactive T cells that can respond to the HLA class I and class II molecules encoded by the HLA class I and II genes of the recipient's HLA haplotype that is not shared with the donor. These alloreactive T cells have the potential to cause a severe and life-threatening graft-versus-host-disease. To prevent such an outcome, bone marrow grafts from haploidentical donors are purged of T cells before being infused into the recipient. Haploidentical transplants are only given to patients who are unable to find an HLA-matched donor. Family members are good candidate donors because all parents and 50% of siblings (on average) have one HLA haplotype in common and one that is different from a patient such as Richard. Unlike Don, who is HLA-haploidentical to Richard, his other sibling Margaret could not be a donor because neither of her HLA haplotypes is shared with Richard.