A 7-year-old boy is admitted to the hospital after his adoptive parents brought him to the emergency department due to fatigue and pallor. Laboratory evaluation reveals pancytopenia with an absolute neutrophil count consistent with severe neutropenia. Bone marrow examination reveals signs of aplastic anemia, and subsequent genetic testing reveals a congenital genomic defect in DNA repair leading to chromosomal instability. A bone marrow transplant is required for treatment. The patient's only living relatives are an identical twin brother and older sister who were both adopted by the same parents. He also has stored umbilical stem cells that were harvested after birth. Which of the following is the best bone marrow transplantation method for this patient?

Question

A 7-year-old boy is admitted to the hospital after his adoptive parents brought him to the emergency department due to fatigue and pallor.  Laboratory evaluation reveals pancytopenia with an absolute neutrophil count consistent with severe neutropenia.  Bone marrow examination reveals signs of aplastic anemia, and subsequent genetic testing reveals a congenital genomic defect in DNA repair leading to chromosomal instability.  A bone marrow transplant is required for treatment.  The patient's only living relatives are an identical twin brother and older sister who were both adopted by the same parents.  He also has stored umbilical stem cells that were harvested after birth.  Which of the following is the best bone marrow transplantation method for this patient?

Quizplus · Accepted Answer

11ec160b_377b_9500_9249_e1b94aaa7f83_MD0001_00 Hematologic stem cell transplantation (HCT) requires identification of a donor with similar human leukocyte antigens (HLAs), polymorphic proteins expressed on the surface of every cell. The most important HLA proteins to match are HLA-A, B, and C, which form major histocompatibility complex class I molecules, and HLA-DP, DQ, and DR, which form major histocompatibility complex class II molecules. Because these HLAs play a vital role in the differentiation between self and nonself, recipients who receive well-matched donor cells have lower rates of graft rejection (ie, host cells attack the donor) and graft-versus-host disease (ie, donor cells attack the host). Donor sources are generally categorized as follows: Autologous: Stem cells harvested from the patient or banked from the patient's cord blood at birth are transplanted to reconstitute the patient's bone marrow. However, autologous transplants cannot be used for congenital genetic disorders because the genetic mutation will be present in all cells harvested from the patient (Choices A and C). Syngenetic: Identical twins have the same genome; therefore, cells transplanted from one identical twin to the other will be an exact HLA match and will not cause graft rejection or graft-versus-host disease. However, syngenetic transplants are not helpful for congenital genetic conditions because any congenital mutation present in one twin will be present in the other (Choice D). Allogeneic donors: Donors who do not have the same genome as the patient are classified as related or unrelated. Related donors: Because HLA alleles are encoded on chromosome 6, each nonidentical sibling has a 25% chance of being an exact HLA match (HLA identical), a 50% chance of sharing half the HLA alleles (haploidentical), and a 25% chance of sharing none of the HLA alleles (HLA mismatch). Therefore, siblings often are tested first for HLA matching because there is a 1:4 chance they will be an exact match. However, unmatched siblings usually are not used for donation because their HLA alleles are not the same as the patient's (Choice E). Unrelated donors: Unrelated donors do not have the same genome as the patient but can have perfect or near-perfect HLA matching; however, extensive searching is often required. Matched unrelated donors generally are best for congenital genetic conditions because the genomic error that leads to the patient's condition will not usually be present in an unrelated individual. Educational objective: Patients who require stem cell transplantation due to a congenital genomic disease typically receive matched unrelated donor cells because they will have matched human leukocyte antigen alleles but will not have the genomic mutation that caused the condition.

A 7-Year-Old Boy Is Admitted to the Hospital After His