Transplantation Between Siblings with Different Blood Types
For transplants between siblings with different blood types, HLA matching is the critical factor for success, while ABO compatibility is secondary and can be managed with appropriate protocols when necessary. 1
Key Considerations for Sibling Transplants with Different Blood Types
HLA Matching vs. Blood Type Compatibility
- HLA matching is the primary determinant of transplant success, with matched sibling donors providing the best outcomes (disease-free survival >95% in certain conditions) 1
- Blood type (ABO) compatibility is secondary to HLA matching in importance
- HLA-identical siblings remain the preferred donor source even with ABO incompatibility
Types of Blood Type Incompatibility
Major ABO incompatibility: Recipient has antibodies against donor red blood cells
- Requires red cell depletion from the graft
- May cause delayed red cell engraftment
- Example: Type O recipient receiving from Type A, B, or AB donor
Minor ABO incompatibility: Donor has antibodies against recipient red blood cells
- May cause hemolysis post-transplant
- Example: Type A, B, or AB recipient receiving from Type O donor
Bidirectional incompatibility: Both major and minor incompatibilities present
- Example: Type A recipient receiving from Type B donor
Impact on Outcomes
- ABO incompatibility does not significantly affect overall survival or disease-free survival when proper management protocols are followed
- Transplant-related mortality remains primarily influenced by:
Management Strategies for ABO-Incompatible Sibling Transplants
Pre-Transplant Considerations
- Complete HLA typing of the entire family is advisable 1
- For major ABO incompatibility:
- Red cell depletion from the stem cell product
- Plasma exchange for recipients with high isohemagglutinin titers
Graft Processing
- Bone marrow is the preferred stem cell source for non-malignant conditions to reduce risk of chronic GVHD 1
- For major ABO incompatibility:
- Red cell depletion techniques
- Density gradient separation
- For minor ABO incompatibility:
- Plasma depletion from the graft
Post-Transplant Management
- Close monitoring for delayed red cell engraftment
- Transfusion support with recipient blood type initially
- Transition to donor blood type after engraftment
- Monitoring for hemolysis in minor ABO incompatibility
Special Considerations by Disease Type
Thalassemia Major
- HLA-matched sibling donors provide excellent outcomes (>90% overall survival) 1
- ABO incompatibility is manageable and should not prevent use of an HLA-matched sibling donor
- Assessment of clinical condition using Pesaro risk score and adequate chelation are critical factors affecting outcomes 1
Sickle Cell Disease
- Young patients with symptomatic SCD who have an HLA-matched sibling donor should be transplanted as early as possible, preferably at pre-school age 1
- Unmanipulated bone marrow or umbilical cord blood from matched sibling donors are the recommended stem cell sources 1
- ABO incompatibility is a secondary consideration to HLA matching
Pitfalls and Caveats
- Do not prioritize blood type matching over HLA matching - an HLA-matched sibling with different blood type is still preferred over alternative donors
- Avoid overlooking the physical and psychological needs of the pediatric sibling donor 2
- Primary care providers should assess the child's physical and psychological ability to undergo the donation procedure 2
- For children with non-malignant disorders, the survival difference between matched sibling donors and matched unrelated donors can be significant (89% vs 63% for metabolic disorders) 3, emphasizing the importance of using sibling donors when available despite blood type differences