With advancements in hematopoietic stem cell transplantation (HSCT), HSCT for infants under 1 year old has gradually evolved from a "forbidden zone" to a viable curative treatment. However, the physiological 特殊性 (physiological peculiarities) of infants—such as immature organ function, pharmacokinetic differences, and long-term quality-of-life concerns—pose significant clinical challenges. Over a decade of exploration, Dr. Liu Zhouyang’s team at Beijing Kyoto Children’s Hospital has developed an individualized HSCT protocol based on "precision conditioning-dynamic immune regulation-multi-dimensional functional protection," significantly improving transplant success rates and long-term outcomes for infants. This article systematically elaborates on their innovative concepts and practical achievements, integrating domestic and international research progress.
Pharmacokinetic Variability: Hepatic metabolic enzyme activity in infants is only 30–50% of adults, doubling the toxicity risk of traditional conditioning regimens.
Immune System Fragility: Immature thymic development leads to T-cell dysfunction, increasing risks of both graft-versus-host disease (GVHD) and infections.
Limited Organ Reserve: Low hepatic and renal functional reserves heighten the risk of multiple organ failure (MOF).
Long-Term Developmental Impact: Post-transplant hormone use may affect skeletal growth and neurocognitive development.
Based on experience with over 200 infant HSCT cases (2016–2025), Dr. Liu proposed a "three-axis individualization model":
Axis 1: Dynamic Dose Adjustment: Conditioning regimens tailored to body weight, body surface area, and hepatic enzyme activity.
Axis 2: Immune Tolerance Induction: Combined umbilical cord blood stem cells with low-dose cyclophosphamide to balance graft-versus-leukemia (GVL) and GVHD effects.
Axis 3: Full-Cycle Functional Protection: Integrated motor rehabilitation, nutritional support, and endocrine monitoring to reduce long-term complications.
A comparative analysis of 78 infants (<12 months) undergoing HSCT by Dr. Liu’s team revealed:
Traditional Bu/Cy Regimen: 28% incidence of hepatic veno-occlusive disease (VOD), 3-year event-free survival (EFS) of only 65%.
Modified Flu/Bu Regimen: Adjusting busulfan (Bu) dose to 120 mg/m² by body surface area, combined with fludarabine (Flu) 40 mg/m², reduced VOD incidence to 5% and increased EFS to 83% [[6][9]].
Key Mechanism: HPLC monitoring of Bu blood levels showed infants cleared Bu 1.5× faster than adults, requiring dosing every 6 hours to ensure area under the curve (AUC) 达标 (attainment).
l Significant Reduction in GVHD Incidence: In 51 umbilical cord blood transplant cases, the incidence of acute GVHD (grade II–IV) was only 12%, significantly lower than 35% in allogeneic peripheral blood transplants (P<0.01), with intestinal GVHD reduced to 8% [[6][9]].
l Infection Prevention Innovation: For EBV reactivation risk, prophylactic rituximab (375 mg/m², q3w) combined with dynamic viral load monitoring reduced EBV-related post-transplant lymphoproliferative disease (PTLD) incidence from 15% to 3% [[2][6]].
Dr. Liu’s team completed 46 infant umbilical cord blood transplants (median age 8 months), with data showing:
Engraftment Success Rate: Median neutrophil engraftment at 14 days (range 12–21 days), median platelet engraftment at 28 days, both superior to bone marrow transplants (P=0.03).
Long-Term Survival Rate: 5-year overall survival (OS) reached 82%, including 89% for inherited metabolic diseases and 76% for malignant hematological diseases [[4][9]].
Typical Case: Baby Xixi, a 3-month-old with hyper-IgE syndrome, achieved complete immune reconstitution and 5-year disease-free survival after 9/10 HLA-matched umbilical cord blood transplant [[4]].
Developed a real-time assessment system using bioelectrical impedance analysis (BIA) and serum markers (e.g., NGAL, Cys-C):
n Early diagnosis sensitivity for acute kidney injury (AKI) increased to 92%.
n MOF incidence reduced to 7% through restrictive fluid management (<130 mL/kg daily) [[6][12]].
Developed a "three-stage exercise intervention protocol" in collaboration with rehabilitation specialists:
n Pre-transplant: Low-intensity respiratory training (30% maximum inspiratory pressure).
n Acute post-transplant phase: Bedside range-of-motion exercises (20 minutes daily).
n Stable post-transplant phase: Progressive resistance training (resistance bands from 0.5 kg to 2 kg).
Follow-up data: 40% faster muscle strength recovery and 0.8 SD improvement in bone mineral density Z-score at 1 year for intervened infants [[13]].
For the high incidence of post-transplant thyroid dysfunction (22%), Dr. Liu’s team proposed:
n Screening Strategy: Quarterly monitoring of TSH, FT4, and IGF-1 levels.
n Intervention Threshold: Initiate levothyroxine or growth hormone replacement when TSH >10 mIU/L or IGF-1 <−2 SD, reducing growth retardation rate from 18% to 6% [[9][12]].
Indicator | Traditional Protocol (Pre-2016) | Liu’s Individualized Protocol (2025) |
3-Year Overall Survival (OS) | 62% | 89% |
Transplant-Related Mortality (TRM) | 23% | 7% |
Severe Infection Incidence | 35% | 12% |
Time to Complete Withdrawal of Immunosuppressants | 18 months | 9 months |
(Data source: Beijing Kyoto Children’s Hospital Hematology Department 2016–2025 cohort analysis) [[6][9]] |
Led the formulation of the Chinese Expert Consensus on Infant HSCT Procedures (2024 Edition), adopted by over 30 pediatric transplant centers.
Established the first national long-term follow-up database for infant transplants (n=326) through the "Multi-Center Research Project on Post-HSCT Functional Recovery," filling a gap in 5+ year outcome data [[6][13]].
Dr. Liu’s team is advancing the following frontier explorations:
1. AI Prognostic Prediction Model: Integrating genomic (e.g., TP53 mutation status), metabolomic (lactate/pyruvate ratio), and radiomic data for complication risk stratification (AUC=0.91).
2. Robot-Assisted Minimally Invasive Marrow Harvesting: Preliminary data show donor marrow collection time reduced to 45 minutes, with CD34+ cell recovery rate increased to 98% [[13]].
3. Umbilical Cord Blood Ex Vivo Expansion: Combined Notch ligand and SCF factor to achieve 50× nucleated cell expansion, overcoming cell dose limitations in infants [[9][12]].
Dr. Liu Zhouyang’s individualized HSCT protocol for infants not only demonstrates technical feasibility through data (5-year OS 89%) but also reshapes the value orientation of transplant medicine through full-cycle functional management—shifting from mere survival to quality of life. This model provides a "Chinese solution" for the global pediatric transplant community, marking China’s international leadership in treating complex hematological diseases in infants. With the deep integration of molecular regulation technologies and regenerative medicine, HSCT is poised to become a safer and more precise "physiological repair"
EN
CN