Clinical Immunology—Bone Marrow Transplant in SCID (Severe Combined Immunodeficiency) For an infant diagnosed with SCID who is receiving a bone marrow (hematopoietic stem cell) transplant, which condition is essential for the donor graft to minimize complications and ensure engraftment?

Introduction / Context:
Severe Combined Immunodeficiency (SCID) is a life-threatening condition characterized by profound defects in T-cell function with variable B- and NK-cell impairment. Curative therapy often involves hematopoietic stem cell transplantation (HSCT). A central principle for HSCT success is appropriate donor–recipient MHC (HLA) matching to promote engraftment and reduce the risk of graft-versus-host disease (GVHD). This question tests understanding of which requirement is essential (“must”) for bone marrow given to an infant with SCID.

Given Data / Assumptions:

• Recipient: infant with SCID requiring HSCT.
• Outcome goals: successful engraftment, immune reconstitution, low GVHD risk.
• Clinical practice emphasizes HLA compatibility and careful management of mature donor T cells.

Concept / Approach:
HSCT success hinges on matching histocompatibility antigens (MHC/HLA). T-cell allorecognition of mismatched HLA is a primary driver of GVHD. While partial (haploidentical) related donors can be used with T-cell depletion, some level of HLA matching remains indispensable to balance engraftment and GVHD risk. Irradiating the graft itself would destroy stem cells; instead, selective T-cell depletion or careful donor selection is used to manage GVHD risk.

Step-by-Step Solution:

Verification / Alternative check:
Clinical HSCT protocols prioritize highest feasible HLA match; where full match is impossible, graft manipulation (e.g., T-cell depletion) is performed, underscoring that HLA matching is the indispensable requirement.

Why Other Options Are Wrong:

• Irradiating the graft would inactivate stem cells.
• Including many mature T cells heightens GVHD risk.
• Requiring a parent donor is unnecessary; matched sibling/unrelated donors are acceptable.
• B-cell depletion alone does not address GVHD risk; T cells are the main concern.

Common Pitfalls:
Confusing irradiated blood products with irradiating the stem-cell graft; assuming kinship guarantees better outcomes regardless of HLA matching.

Final Answer:
Come from a donor who shares key MHC (HLA) alleles with the recipient