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XTS system utilized a modular design that minimizes setup time. Patients receive the photoactivable drug (8-MOP) after which various components within the XTS system collect blood, segregate the leukocytes and photoactivate them with precise levels of ultraviolet energy the newly photoactivated cells and concentrated blood fractions are all returned to the patient. Two types of bowl are proposed: 120 and 225 ml capacity. With this last one, only three cycles are needed. The microprocessors for the XTS system take input from the operator sensors, and fluid logic controller, then process it into information the fluid logic module uses move blood components to and from the patient and the various components of the system. The UVAR XTS fluid logic controller is a series of valves and pressure transducers connected to a flexible membrane that is a mirror image of the fluid logic module. As the point of the contact for the module, the controllers applies pressure to specific “access” which then activates fluid movement fluid pathways and valve operations. Externally, the fluid logic module is a molded acrylic cassette that is covered by two flexible membranes. Internally, multiple chambers pathways, and valves rely on pneumatic pressure to establish appropriate fluid pathways, open and close valves, and move fluid to and from the patient, the centrifuge, the collection bags and the photoactivation chamber. Finally, it is a fully automatic system. Numerous parameters (procedure and defaults) are controlled by the mean of a special key which integrates a microprocessor. Quality and quantify of the buffy coat is adjusted by the fluid logic module. Time irradiation is variable (correlated with the hematocrit of the buffy coat). The UVAR system has undergone numerous testing to comply with the appropriate industry standards and to receive technical certifications: –IEC 601-1; –ISO 9001 (BSI); –EN 46001 (BSI); –889/336/EEC Electromagnetic compatibility. 2.4. “Off line” technique (UV-MATIC irradiator) (Photo 3
Photo 3.
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| Table 1. Evaluation of the different processes |
 | VILBER LOURMAT | UVAR | XTS | | |
| Irradiation time | <20 min | 120 min | ≈40 min variable | |
| Total duration | ≈2 h | 3 h | 2 h 30 min | |
| Automatism | ± | − | +++ | |
| Control energy | + | − | + | |
| Extra corporeal volume | 200 ml | 250 | Depends of bowl capacity | |
| Mononuclear cells yield | +++ | ++ | + | |
| Process control | ± | ± | +++ | |
| Table 2. Characteristics of the different techniques |
| VILBER LOURMAT (spectra) | Therakos | | ||
| UVAR | XTS | | ||
| Features | Two independent steps | In line | In line | |
| anticoagulation | ACD FA | Heparin | Heparin | |
| Blood volume processed (l) | 6.6 | 2.170 | 2 | |
| Collect pump | + | + | − a | |
| Irradiation | With a specific device | Integrated | Integrated | |
| Certification CE | No | Yes | Yes | |
| Buffy coat collection | Continuous (two accesses) | Discontinuous (one access) | Discontinuous (one access) | |
| Product volume | 50–150 | 540 | ≈300 | |
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a
Fluid logic module. |
With UVAR systems, we used heparin diluted in saline solution. We infuse, before starting, the procedure a bolus of heparin (2000–3000 units) and after the blood is anticoagulated continually during the procedure with a special pump for UVAR 1st generation; with the fluid logic module when using XTS machine.
With SPECTRA, we use ACD FA with 1/9 ratio.
With Therakos system irradiation is done in a special chamber: the PHOTOCEPTOR™. Its thickness is 1.4 mm and its volume is 135 ml. The volume collected with UVAR is 540 ml, and about 300 ml with XTS system. Cells incubate in the chamber at a flow of 100 ml/min. The time of single cell irradiation is between 17 and 35 min. With XTS system, this parameter is better controlled and more homogenous.
The life of the lights is controlled and we have instructions to change the whole set of lamps every 150 h.
With UV-MATIC irradiator, the irradiation zone is 22×35 cm and is submitted to a constant horizontal rotation (60 rpm) during irradiation. Its thickness is maintained below 3 mm by use of two quartz plate is automatically monitored by means of an integration which allows precise energy programming.
The different parameters are summarized on the Table 3.
| Table 3. Results: Hematological parameters of the different concentrates |
| VILBER LOURMAT (spectra) | UVA*N=37 | XTS N=50 | | |
| Hematocrit (%) | 0.9–1.2 | 3.61 ±0.90 | 2.02±0.64 | |
| Volume (ml) | 50 140 | 540 | 280 | |
| WBC×109/concentrate | 15.9±9.7 | 3.4±0.67 | 2.80±1.64 | |
| Mononuclear cells×109/concentrate | 15.2±9.8 | 2.02±1.29 | 1.10±0.69 | |
Leukocyte collection with the SPECTRA is much higher than yields obtained with both Therakos apparatus (classic UVAR and XTS system).
We can conclude that we irradiate and re-infuse much more cells with “off line” technique. May be, this procedure is not exactly the same in comparison with Therakos processes.
With Spectra collection, we could consider that the effects of photopheresis are in relation not only with photopheresis but also with leukapheresis (cell soustraction).
Beside the certification of these types of apparatus and before routine use we have to organize photopheresis procedures through written processes, guidance manual, signification of the alarms, listing the security and staff training.
In addition, we must have a maintenance contract and organize our materiovigilance network through the risk management of photopheresis (risk analysis, risk assessment, risk evaluation and risk reduction).
In manual technique, we can modify the flow rate and so the quality of the mononuclear cells concentrate. It is the case of blood cell separator and 1st version of UVAR.
With XTS machine, the harvest of the cells is automatically adapted with the vein pressure and performed with the fluid logic module (pneumatic system to control blood flow and hematocrit).
With manual technique, we have to note the general parameters of the procedure of cells collection. Only a very few are available directly from the machine. UV-MATIC irradiator gives only the parameters we have programmed. Only the energy received by the cells are controlled.
XTS machine: numerous parameters of the processes are registered and we can obtain them by the microprocessor key. For example, we have a summary of the alarms, treatment time, photoactivation time, Buffy coat volume, hematocrit, maximum extracorporeal volume (Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7).
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Fig. 1. Total System Errors. | ||
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Fig. 2. Total Alarms. | ||
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Fig. 3. Treatment Time (min). | ||
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Fig. 4. Photoactivation Time (min). | ||
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Fig. 5. Buffy Volume (m/s). | ||
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Fig. 6. Buffy HCT %. | ||
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Fig. 7. Max Extracorporeal Volume. | ||
| Table 4. Lymphocytes subsets of the concentrate |
| T | B | T4 | T8 | | |
| Lymphocytes subsets (%) | 76.68±6.7 | 13.62±5.46 | 48.63±6.98 | 28.48±1.76 | |
Irradiation+8-MOP: Lymphocytes proliferation tests (with non-specific mitogen) (Fig. 8).
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Fig. 8. Lymphocyte proliferation test with PHA and PW. | ||
Viability: We can control the viability test on the irradiated cells and generally we find a good percentage of viability (90–95%).
Extensive research performed with UVAR system or VILBER LOURMAT system has validated the efficacious combination of cells, drug and light used in photopheresis.
Actually, excepted in some indications (chemical trials with UVAR system), this therapeutic is not still validated in almost all the diseases.
If we compare the two principles actually available, we can conclude that they are very different in terms of cells harvesting, safety, efficacy of the procedures.
The 2nd generation of UVAR (XTS) is a complete automatic system using a closed device to achieve the treatments.
This system is validated in terms of certification by numerous notified organisms.
With the two independent steps technique (VILBER LOURMAT), we use a simple procedure divided in cell collection and irradiation step before re-infusion into the patient.
The safety and security of this system remain a problem because it does not use a closed device, with manual operations (transfer in an EVA bag, irradiation, re-infusion). This system has not still got technical certification. Vilber Lourmat has to do rigorous testing to comply with the appropriate industry standards. In both techniques, the protocols are empiric based only on previous experience. The disponibility of liquid psoralen remains a problem when we use the two independent steps technique. Some new techniques are in evaluation actually. BAXTER has developed the Intercept technique to inactivate platelets or plasma [6] with a new variety of psoralen. We can suppose that this technic could be applied for ECP only by minor modifications of the platelet process.
Photopheresis therapy constitutes certainly a promise direction to treat patients suffering from serious diseases. The available techniques on the market can resolve some problems but are not perfect to achieve our protocols. The companies have to improve these techniques and to introduce more safety and more control on the process itself (irradiation: energy received). To develop new concepts of ECP, we have to better understand the mechanisms of photopheresis efficacy, the side effects of such treatment, and the consequences on the cells and immunological system of the patient. In this area of development, we must imagine new concepts of photopheresis, may be with new photoactivable molecules.
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[3]. [3] . Production of singlet oxygen and superoxides radicals by psoralen and their biological significance. Biochem Biophys. Res. Commun. 1983;112:638–646. CrossRef
[4]. [4] . Photoconjugation of 8-methoxypsoralen with proteins. Photochem. Photobiol. 1979;29:1123–1127.
[5]. [5] . In vitro kinetics of 8-methoxypsoralen penetration into human lymphoid cells. Photodermatol. Photoimmunol Photomed. 1992;7:1–3.
[6]. [6] Photochemical inactivation of viruses and bacteria in platelet concentrates by use of a novel psoralen and long-wavelength ultraviolet light. Transfusion. 1997;37:423–435. MEDLINE
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1 Laboratoires PROMEDICA––Levallois Perret––France.
PII: S1473-0502(02)00100-3
doi:10.1016/S1473-0502(02)00100-3
© 2003 Elsevier Science Ltd. All rights reserved.
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