What are the objective laboratory criteria that define successful engraftment after stem‑cell transplantation in adults, including neutrophil recovery, platelet recovery, and donor chimerism thresholds?

Successful Engraftment Criteria Post Stem Cell Transplantation

Engraftment is defined as a sustained absolute neutrophil count (ANC) ≥500/mm³ and platelet count ≥20,000/mm³ for at least 3 consecutive days without transfusions. 1, 2

Neutrophil Recovery Criteria

• Primary threshold: ANC ≥500/mm³ (0.5 × 10⁹/L) sustained for 3 consecutive days defines myeloid engraftment 1, 2
• The first day neutrophils reach ≥0.5 × 10⁹/L represents valid myeloid recovery, as neutrophil counts continue to rise after this threshold even without G-CSF support 3
• Timing expectations:
  • Median engraftment occurs at 22 days post-transplant in unrelated allogeneic recipients (range: 6-84 days) 1
  • Autologous transplant recipients typically achieve neutrophil recovery at a median of 10 days 4

Platelet Recovery Criteria

• Primary threshold: Platelet count ≥20,000/mm³ sustained for 3 consecutive days without platelet transfusions 1, 2
• Some centers use ≥50,000/mm³ as an alternative threshold for complete platelet engraftment 1
• Autologous transplant recipients typically achieve platelet recovery at a median of 13 days 4

Donor Chimerism Thresholds

Complete donor chimerism (≥95% donor cells) is the gold standard for successful allogeneic engraftment. 1

Chimerism Assessment Timing and Interpretation

• Day 21 bone marrow chimerism is critically predictive of sustained engraftment success 5

  • 100% donor chimerism at day 21: 98% engraftment rate at median 22 days 5
  • 90-99% donor chimerism: 100% engraftment but delayed to median 29 days 5
  • <90% donor chimerism: only 68% engraftment at median 37 days 5

• Long-term chimerism patterns vary significantly by graft source 6:

  • Cord blood recipients maintain higher donor chimerism: 100% at 6 months, 99.2% at 12-24 months 6
  • Non-cord blood recipients show declining chimerism: 93.8% at 6 months, 91% at 12 months, 75% at 24 months 6

Lineage-Specific Chimerism

• Myeloid (CD15+) chimerism: Cord blood achieves 100% vs. 85.2% for other sources at 6 months 6
• T-cell (CD3+) chimerism: Cord blood achieves 93% vs. 70% for other sources at 6 months 6
• Molecular methods (short tandem repeat, SNP, indel markers) are more analytically sensitive than cytogenetic analysis for chimerism assessment 1

Important Caveats and Clinical Pitfalls

Distinguishing Engraftment from Graft Dysfunction

• Poor graft function (PGF) can occur despite complete donor chimerism (>95%), manifesting as persistent cytopenias after day +28 1
• PGF is distinct from graft rejection, which shows absent or minimal donor chimerism 1
• The EBMT defines PGF as "two or three cytopenias more than two weeks after day +28, in the presence of >95% donor chimerism" 1

Factors Affecting Engraftment Success

• CD34+ cell dose is the strongest predictor of engraftment kinetics in both autologous and allogeneic transplantation 4

  • Autologous: >10 × 10⁶/kg CD34+ cells for optimal neutrophil recovery 4
  • Autologous: >7 × 10⁶/kg CD34+ cells for optimal platelet recovery 4
  • Single cord blood unit: minimum 1.5 × 10⁵/kg CD34+ cells prefreeze 1
  • Double cord blood units: minimum 1.0 × 10⁵/kg CD34+ cells per unit 1

• Prior alkylating agent exposure (particularly melphalan) reduces stem cell harvest quality and may impair engraftment 1

• Graft failure rates vary by donor type: 5-10% for matched sibling donors, higher for haploidentical and mismatched donors 2

When to Suspect Engraftment Failure

• Primary graft failure occurs more frequently with cord blood (4.3%) compared to other sources (0.8%) 6
• Persistent cytopenias beyond expected engraftment windows warrant chimerism analysis 1
• Mixed chimerism (<95% donor) requires close monitoring and may necessitate donor lymphocyte infusion or second transplant depending on clinical context 1, 7