Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Patients with Chronic Graft-versus-Host Disease: A First-in-Human Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Design and Procedures
2.3. Safety and Tolerability
2.4. Organ, Performance, and Quality of Life Assessments
2.5. Statistical Methods
3. Results
3.1. Patients and Treatments
3.2. Safety and Tolerability
3.3. Organ, Performance, and Quality of Life Assessments
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Time Point | ||||||
---|---|---|---|---|---|---|
Investigation | Screening (Baseline) | ECP, Day 1 | ECP, Day 2 | Post-ECP, Day 4 ± 1 | Post-ECP, Day 16 ± 2 | Controls, Every 3 Months |
Vital signs | x | x | x | x | ||
ECG | x | x | ||||
Haematology | x | x * | x | |||
Clinical chemistry | x | x * | x | |||
Urine analyses | x | x * | x | |||
Conceivable Adverse Events | x | x | ||||
Adverse Events | x | x | x | x | ||
Organ, performance, and QoL assessments | x | x * | x |
Type of Adverse Event | Number of Patients | Number of Grade 1 | Number of Grade 2 | Number of Grade 3 | Relation to Study Medication |
---|---|---|---|---|---|
Clotting in buffy | 4 | 0 | 4 | 0 | Possibly |
Cold like symptoms | 3 | 3 | 1 | 0 | Unlikely |
Dysuria | 1 | 0 | 3 | 0 | Possible |
Respiratory infection | 2 | 0 | 1 | 1 | Possible |
Skin worsening | 1 | 0 | 1 | 0 | Possible |
Migraine | 1 | 0 | 0 | 1 | Unlikely |
Flue like symptoms | 1 | 1 | 0 | 0 | Unlikely |
Elevated INR | 1 | 1 | 0 | 0 | Unlikely |
Prickling around mouth | 1 | 1 | 0 | 0 | Possible |
UVI | 1 | 0 | 1 | 0 | Possible |
Malaise | 1 | 1 | 0 | 0 | Unlikely |
Sore throat, pain toes and hip | 1 | 1 | 0 | 0 | Unlikely |
Prolonged QTc interval | 1 | 1 | 0 | 0 | Unlikely |
Type of Adverse Event | Number of Patients | Number of Grade 1 | Number of Grade 2 |
---|---|---|---|
Nausea | 4 | 19 | 2 |
Vomiting | 2 | 1 | 1 |
Headache | 4 | 10 | 3 |
Photosensitivity | 0 | 0 | 0 |
Chills | 2 | 4 | 0 |
Target | Scoring Tool | Scoring Scale | Baseline (Mean Score, min.- max.) | Last Control (Mean Score, min.- max.) |
---|---|---|---|---|
Skin | Modified organ scoring system | 0–3 (0 = no symptom) | 2.6 (1–3) | 1.6 (1–2) |
Skin | Body surface area % | 0–100% (0 = no area affected) | 15.8 (7–30) | 5.0 (3–7) |
Pruritus | Visual analogue scale | 0–10 (0 = no symptom) | 3.3 (0–7) | 1.4 (1–2) |
Mouth | Modified organ scoring system | 0–3 (0 = no symptom) | 1.6 (0–3) | 1.4 (0–2) |
Eye, right | Schirmer’s test | 1–4 (1 = normal) | 3.0 (1–4) | 4.0 (4–4) |
Eye, left | Schirmer’s test | 1–4 (1 = normal) | 3.6 (3–4) | 4.0 (4–4) |
Performance | Modified organ scoring system | 0–3 (0 = no symptom) | 1.2 (1–2) | 0.8 (0–1) |
Gastrointestinal tract | Modified organ scoring system | 0–3 (0 = no symptom) | 0.4 (0–1) | 0.4 (0–1) |
Function | Karnovsky’s performance scale | 1–100 (0 = low function) | 74 (70–90) | 82 (70–100) |
Skindex, emotions | Questionnaire | 0–100 (0 = no symptom) | 22.0 (8–48) | 10.2 (0–30) |
Skindex, symptoms | Questionnaire | 0–100 (0 = no symptom) | 30.4 (21–39) | 24.2 (17–36) |
Skindex, function | Questionnaire | 0–100 (0 = no symptom) | 19.6 (2–56) | 13.4 (2–42) |
Skindex, single item | Questionnaire | 0–100 (0 = no symptom) | 10.0 (0–25) | 10.0 (0–50) |
EORTC30, functional | Questionnaire | 0–100% (0 = low function) | 76.2 (70–100) | 82.0 (57–100) |
EORTC30, symptoms | Questionnaire | 0–100% (0 = low level of symptom) | 23.4 (7–40) | 20.0 (3–50) |
EORTC30, global health status | Questionnaire | 0–100% (0 = low state) | 65.2 (42–75) | 61.4 (16–83) |
FACT-G, total score | Questionnaire | 0–108 (0 = low state) | 86.8 (63–99) | 88.4 (70–97) |
FACT-BMT, subscale score | Questionnaire | 0–40 (0 = much concern) | 27.8 (22–35) | 29.6 (18–36) |
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Christensen, E.; Foss, O.A.; Quist-Paulsen, P.; Staur, I.; Pettersen, F.; Holien, T.; Juzenas, P.; Peng, Q. Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Patients with Chronic Graft-versus-Host Disease: A First-in-Human Study. Pharmaceutics 2021, 13, 1558. https://doi.org/10.3390/pharmaceutics13101558
Christensen E, Foss OA, Quist-Paulsen P, Staur I, Pettersen F, Holien T, Juzenas P, Peng Q. Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Patients with Chronic Graft-versus-Host Disease: A First-in-Human Study. Pharmaceutics. 2021; 13(10):1558. https://doi.org/10.3390/pharmaceutics13101558
Chicago/Turabian StyleChristensen, Eidi, Olav A. Foss, Petter Quist-Paulsen, Ingrid Staur, Frode Pettersen, Toril Holien, Petras Juzenas, and Qian Peng. 2021. "Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Patients with Chronic Graft-versus-Host Disease: A First-in-Human Study" Pharmaceutics 13, no. 10: 1558. https://doi.org/10.3390/pharmaceutics13101558
APA StyleChristensen, E., Foss, O. A., Quist-Paulsen, P., Staur, I., Pettersen, F., Holien, T., Juzenas, P., & Peng, Q. (2021). Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Patients with Chronic Graft-versus-Host Disease: A First-in-Human Study. Pharmaceutics, 13(10), 1558. https://doi.org/10.3390/pharmaceutics13101558