Making ECP Work for Kids: Practical Guidance for GVHD Treatment

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy increasingly used in the management of acute and chronic graft-versus-host disease (GVHD), particularly in pediatric patients for whom traditional therapies may fall short. Despite promising outcomes, pediatric ECP remains a niche practice characterized by significant variability in technique, access, safety protocols, and clinical outcomes. This post integrates insights from two comprehensive reviews to explore practical and clinical aspects of pediatric ECP, combining real-world experience with calls for standardization and research.

1. What is ECP and How Does it Work?

ECP is a cellular therapy involving:

• Leukapheresis to collect white blood cells (WBCs)

• Incubation with 8-methoxypsoralen (8-MOP), a photosensitizer

• Exposure to UVA light

• Reinfusion of the treated WBCs into the patient

  
  

This process is thought to promote immune tolerance by shifting immune responses from inflammatory (Th1) to regulatory (Th2) profiles, inducing apoptosis of pro-inflammatory cells, and increasing regulatory T-cell populations. While the exact mechanism in GVHD remains unclear, multiple pathways including cytokine modulation, monocyte differentiation, and B-cell regulation have been implicated.

2. ECP Systems: In-Line vs. Off-Line

Feature	In-Line (UVAR XTS, CELLEX)	Off-Line (COBE Spectra, COM.TEC, etc.)
System Type	Closed, automated	Open, manual
Leukapheresis & Irradiation	Integrated	Performed on separate devices
Flow Type	Discontinuous (XTS) / Continuous (CELLEX)	Continuous preferred
Extracorporeal Volume (EV)	XTS: up to 480 mL, CELLEX: ~216–266 mL	Variable (lowest: COM.TEC at 137 mL)

Continuous flow systems yield more mononuclear cells (MNCs) and reduce EV, making them preferable for pediatric use.

3. Indications and Clinical Outcomes in Pediatrics

In children, ECP is primarily used for:

• Steroid-refractory acute GVHD: response rates 50–100%, depending on organ involvement

• Chronic GVHD: ~60% response rate; enables steroid tapering

  
  

However, all current data come from case series or observational studies—no randomized controlled trials (RCTs) have included patients under 17 years. While adult RCTs suggest efficacy, extrapolation to pediatrics requires caution.

4. Technical and Clinical Challenges

A. Extracorporeal Volume (EV)

High EV can cause hypotension and hemodynamic instability in low-weight children.

Strategies to minimize risk:

• Use lower-EV devices (e.g., CELLEX, COM.TEC)

• Prime circuit with red blood cells (RBCs) or 5% albumin

• Administer saline or albumin boluses pre-procedure

Device	EV (mL)	Min. Weight Recommendations
UVAR XTS	480	>40 kg (with priming)
CELLEX	216–266	>30 kg (without priming)
COM.TEC	137	<30 kg (with priming preferred)

B. Vascular Access

• Central venous catheters (single- or double-lumen) are commonly used

• Catheter-related infections and occlusions are the most frequent complications

Reported Complication Rates:

• Infections: 3.7–7%

• Occlusion: ~4%

• Preventive measures: urokinase/tPA, aseptic technique, dedicated central lines

  
  

C. Hematologic and Metabolic Considerations

ECP can cause modest drops in hematologic parameters:

• Hemoglobin: median drop of 1.5 g/dL

• Platelets: median drop of 17%

Typical Pre-Procedural Lab Cutoffs:

Parameter	Threshold
Hematocrit	>24–28%
Platelet count	>20,000–50,000/µL
WBC count	>1,000/µL

There is no consensus on ideal target cell yields or on correlation between infused MNC counts and clinical efficacy.

5. Scheduling and Duration of Therapy

Protocols vary widely:

• Initial Phase: 2–3 treatments/week

• Maintenance: Decrease to every 2–4 weeks based on response

• GVHD Monitoring: Weekly for aGVHD, every 1–2 months for cGVHD

Study	Initial Schedule	Tapering
Kanold	3x/week for 3 weeks	Gradual taper
Messina	2x/week for 1 month, biweekly for 2 months	Then monthly for 3+ months
Foss	No difference found between 1x vs 2x/week	Schedules individualized

There is no evidence that more intensive schedules yield better outcomes.

6. Alternative Techniques: Mini Buffy Coat ECP

For children who cannot tolerate leukapheresis:

• Mini buffy coat method involves collecting 100–200 mL of whole blood

• Buffy coat is prepared and irradiated in a closed system

• Red cells, plasma, and platelets are returned to the patient

Clinical Results:

• 84% response rate in pediatric aGVHD

• Strong correlation between higher WBC dose/kg and response

  
  

This technique may be a valuable alternative in patients <20 kg.

7. Gaps in Knowledge and Recommendations

Despite widespread clinical use, pediatric ECP suffers from a lack of standardization and rigorous evidence. Key areas needing further research include:

Domain	Current Gaps	Recommendations
Patient selection	No consensus on minimum weight or lab cutoffs	Develop evidence-based eligibility guidelines
Product evaluation	No QC benchmarks or ideal cell dose/kg	Define and validate efficacy markers
Anticoagulation protocols	Heparin vs. citrate strategies vary by center	Standardize anticoagulation practices based on risk
Scheduling	Highly variable schedules	Conduct studies comparing intensive vs. tapered regimens
Vascular access	Complications common	Guidelines for catheter type and maintenance
Alternative collection methods	Mini ECP underutilized	Further evaluate in RCTs or multicenter trials

8. Conclusion

ECP is a safe, well-tolerated, and potentially effective treatment for pediatric GVHD, particularly in steroid-refractory cases. However, practice varies widely, and most evidence is derived from observational data. To expand safe access and improve outcomes, standardized protocols and prospective studies—especially randomized trials in pediatric populations—are urgently needed. Until then, successful ECP in children will continue to rely on experienced multidisciplinary teams, careful patient selection, and vigilant monitoring.

Have experience with pediatric ECP in your institution? Let us know what’s working—and what’s not.

References

DeSimone RA, Schwartz J, Schneiderman J. Extracorporeal photopheresis in pediatric patients: Practical and technical considerations. J Clin Apher. 2017; 32: 543–552. https://doi.org/10.1002/jca.21534

Sniecinski, I., & Seghatchian, J. (2017). Factual reflections and recommendations on extracorporeal photopheresis in pediatrics. Transfusion and Apheresis Science, 56(2), 118-122. https://doi.org/10.1016/j.transci.2017.03.013Get rights and content