Engraftment Probability in Hematopoietic Stem Cell Transplantation
Engraftment success in HSCT is exceptionally high, with 92-98% of patients achieving durable engraftment, though timing and complications vary significantly by donor type, conditioning intensity, and patient age. 1, 2, 3
Engraftment Rates by Transplant Type
Matched Sibling Donor (MSD) Transplantation
- Engraftment occurs in 95-98% of patients receiving HLA-matched sibling donor grafts 2, 3
- Median time to engraftment is 22 days (range 6-84 days) for unrelated allogeneic recipients 1
- Graft failure occurs in only 5-10% of MSD HSCT recipients 1
Alternative Donor Transplantation
- Umbilical cord blood transplantation achieves 92.9% neutrophil engraftment by day 60, with median time of 23 days 4
- Unrelated donor transplants show comparable engraftment rates to matched siblings, with 98% durable engraftment documented in large series 3
- Haploidentical and mismatched donors carry higher graft failure risk, particularly with reduced-intensity conditioning 1
Reduced-Intensity Conditioning (RIC)
- 86% engraftment rate observed in patients with active refractory/relapsed disease receiving sequential RIC regimens 5
- Most patients develop initial mixed donor/host chimerism after nonmyeloablative conditioning, with gradual conversion to full donor chimerism over weeks to months 6, 7
- Full donor chimerism achieved at median of 14 days in cord blood recipients after RIC 4
Engraftment Definition and Criteria
Engraftment is defined as sustained absolute neutrophil count (ANC) >500/mm³ and platelet count >20,000/mm³ for >3 consecutive days without transfusions 1
Key Milestones
- Neutrophil engraftment: Typically occurs first, median 20-23 days post-transplant 1, 4
- Platelet engraftment: Occurs later, with 42.9% achieving independence by day 100 in cord blood recipients 4
- Complete donor chimerism: May take weeks to months, particularly after reduced-intensity regimens 6, 7
Factors Affecting Engraftment Success
Patient-Related Factors
- Age significantly impacts outcomes: Patients >13-16 years have higher transplant-related mortality and potentially delayed engraftment 1, 8
- Disease status: Active refractory/relapsed disease shows 86% engraftment despite higher-risk profile 5
- Prior chemotherapy exposure: Preceding chemotherapies associated with higher degrees of donor chimerism 7
Transplant-Related Factors
- Conditioning intensity: Myeloablative conditioning provides more rapid, complete engraftment but higher toxicity; RIC shows initial mixed chimerism 8, 6, 7
- Graft source: G-CSF-mobilized peripheral blood grafts achieve higher donor chimerism levels than bone marrow 7
- Donor type: Matched siblings have lowest graft failure (5-10%); alternative donors have incrementally higher risk 1
- T-cell depletion: Increases graft failure risk 1
Clinical Pitfalls and Monitoring
Early Predictors of Graft Failure
- Low donor T-cell chimerism on day 14 strongly predicts graft rejection (P=0.003) 7
- Low donor NK-cell chimerism on day 14 also predicts rejection (P=0.004) 7
- Earlier establishment of donor NK-cell chimerism associates with improved progression-free survival (P=0.02) 7
GVHD Considerations
- High T-cell chimerism on day 28 correlates with increased acute GVHD probability (P=0.02) 7
- GVHD prophylaxis regimens affect engraftment kinetics but not ultimate success rates 1
Critical Monitoring Points
- Serial chimerism analysis of peripheral blood cell subsets (T-cells, NK-cells, myeloid cells) provides actionable information for early intervention 7
- Day 14 and day 28 assessments are critical timepoints for predicting graft rejection or GVHD 7
- Patients may achieve complete remission while still mixed chimeras, particularly after RIC (19 of 41 patients in one series) 7
Age-Specific Outcomes
Pediatric Patients (<16 years)
- Overall survival: 95%; Event-free survival: 93% in sickle cell disease cohorts 1
- Lower rates of acute GVHD (12.6%) and chronic GVHD (14.6%) 1