Treatment of extensive chronic graft-versus-host disease with extracorporeal photochemotherapy

Extracorporeal photochemotherapy (ECP; photopheresis), an immunomodulatory therapy developed for cutaneous T-cell lymphoma, has shown promise in treating chronic graft-versus-host disease (cGvHD) in uncontrolled studies. The purpose of this study was to further examine the effects of ECP on cGvHD. ECP (administered initially 3 times weekly on alternating days) was retrospectively evaluated in 14 patients with extensive cGvHD following allogeneic hematopoietic stem cell transplantation. The median time from transplantation to ECP initiation was 29 months (range, 5-96 months). The median number of concomitant baseline treatments per patient was 3 (range, 0-5). During a median ECP duration of 17 months (range, 3-44 months), 3 patients (21%) achieved a complete cutaneous response (100% improvement), 4 patients (29%) achieved a partial cutaneous response (> or =50% improvement), and 7 patients (50%) had stable skin disease. The median time to response was 6 months (range, 2-15 months), and the median response duration was 5 months (range, 1-31 months). At endpoint, responses were ongoing in 4 patients. Resolution or improvement was noted in arthralgia (5/7 patients), oral changes (3/7), elevated liver enzymes (3/5), dry eyes (2/5), joint stiffness (3/3), pulmonary disease (1/3), and thrombocytopenia (1/1). Because of a favorable response, 11 of 13 patients (85%) who received prednisone at baseline were able to taper (7/13; 54%) or discontinue (4/13; 31%) this medication, and 12 of 14 patients (86%) were able to taper (11/14; 79%) or discontinue (1/14; 7%) ECP. Five-year posttransplantation survival was 77%. Our results suggest that adjunctive ECP improves cutaneous and extracutaneous manifestations of cGvHD and has a steroid-sparing effect.     

Extracoporeal photochemotherapy in cutaneous lupus erythematosus

We report two female subjects with therapy-resistant cutaneous lupus erythematosus (LE), one with subacute cutaneous and the other chronic discoid LE, both treated with extracorporeal photochemotherapy (ECP). The responses after six and eight cycles of ECP led to a prolonged remission of 18 and 11 months, respectively. ECP seems to be a treatment option for patients not responding to or showing unwanted side-effects during conventional standard therapy.     

Effect of photodynamic therapy in combination with ionizing radiation on human squamous cell carcinoma cell lines of the head and neck

Photodynamic therapy (PDT) is a promising treatment modality for head and neck, and other tumours, using drugs activated by light. A second generation drug, 5-aminolaevulinic acid (5-ALA), is a precursor of the active photosensitizer protoporphyrin IX (PpIX) and has fewer side-effects and much more transient phototoxicity than previous photosensitizers. We have investigated the effect of 5-ALA mediated PDT in combination with gamma-irradiation on the colony forming ability of several human head and neck tumour cell lines. The effect of treatments on the DNA cell cycle kinetics was also investigated. Our results indicate that the combination of 5-ALA mediated PDT and gamma-irradiation results in a level of cytotoxicity which is additive and not synergistic. 5-ALA mediated PDT had no discernible effect on DNA cell cycle distributions. gamma-irradiation-induced cell cycle arrest in G2 did not enhance the phototoxicity of 5-ALA.     

Hepatitis from 5-methoxypsoralen occurring in a patient with previous flucloxacillin hepatitis

A 55-year-old woman with psoriasis vulgaris was treated with oral 5-methoxypsoralen and UVA photochemotherapy. After 40 treatments over 3 months she became unwell with hepatitis attributable to the psoralen. Six years earlier she developed cholestatic hepatitis to flucloxacillin. A previous history of drug-induced reactions should be sought before prescribing further drugs with similar adverse effects.     

Optical characteristics of the canine prostate at 665 nm sensitized with tin etiopurpurin dichloride: need for real-time monitoring of photodynamic therapy

PURPOSE: Photodynamic therapy (PDT) is an emerging, minimally invasive therapy for prostate cancer that depends on the sequestration of a photosensitizing drug within targeted tissue. The photosensitizer is subsequently activated by light of a specific wavelength, resulting in destruction of the targeted tissue. Successful treatment requires knowledge of the optical properties of the target tissue, a critical element for therapy. MATERIALS AND METHODS: Adult canines were injected with tin etiopurpurin dichloride (1.0 mg/kg) as a liposome emulsion vehicle in saline 24 hours prior to light treatment. Laser light was delivered to the prostate via a 400 microm optical fiber fitted with a 2.0 cm cylindrical diffuser and optical properties of the prostate were measured. RESULTS: In this study we determined the attenuation coefficient and critical fluence in the canine prostate. Our studies shown that the attenuation coefficient is not uniform but higher at the base (average for all animals 2.59 to 2.79 cm-1) than in the mid section or apex of the prostate (1.71 to 1.90 cm-1). Significant differences among dogs (0.11 to 12.70 cm-1) were found. In some cases we observed a fluctuation of the attenuation coefficient during treatment. We also established experimentally the minimum energy (1449 mJ/cm2) needed (critical fluence) to produce necrosis. Experimentally establishing the values of effective attenuation and critical fluence is necessary to predict the area of ablation during PDT and protect surrounding organs from over treatment. CONCLUSIONS: Based on our results it is evident that for PDT of the prostate to be successful the optical parameters of the prostate must be measured and monitored during treatment. We suggest that the optimum way of doing this is real-time computerized monitoring combined with simulation PDT.     

光动力治疗中晚期中央型肺癌的临床初探

目的：初步探讨光动力疗法对中晚期中央型肺癌患者近期的疗效。方法：选择同意接受光动力治疗的有支气管阻塞症状，或上腔静脉综合征的中晚期中央型肺癌患者10例，在治疗前接2mg／kg体质量剂量静注光敏剂Photo—frin或Photoson，36～48h后在纤支镜下用630nm波长的红光激光照射肿瘤500s。结果：10例患者SR7倒，MR2例，NR1例。结论：光动力治疗能明显缓解中央型肺癌惠者的梗阻症状，近期疗效明显，能改善其生活质量。     

A randomized controlled trial of narrowband ultraviolet B vs bath-psoralen plus ultraviolet A photochemotherapy for psoriasis

BACKGROUND: In 1991, consensus guidelines recommended psoralen plus ultraviolet A photochemotherapy (PUVA) for those requiring second-line therapy for psoriasis. Narrowband (TL-01) UVB has since become more widely available, replacing the less effective broadband sources. Objectives To compare the efficacy of TL-01 UVB phototherapy and trimethoxypsoralen (TMP) bath-PUVA for chronic plaque psoriasis. PARTICIPANTS AND METHODS: A randomized, observer-masked, intraindividually controlled, paired (half-body) study was done in the Photo(chemo)therapy Unit in Ninewells Hospital and Medical School, Dundee. The study comprised 28 patients (skin phototypes I-III) with chronic plaque psoriasis. Each patient's body halves (sagittal plane) were treated independently, one-half with TL-01 UVB, the other with bath-PUVA. Both treatments were administered according to standard, optimized regimens. Treatment was continued until clearance or minimal residual activity (MRA), or a maximum of 30 treatments. The main outcome measures were treatments and time to clearance/MRA, the proportion reaching clearance/MRA, change in psoriasis severity score (scaling, erythema and induration) and remission durations. RESULTS: Of 18 who completed the study, all reached clearance/MRA with TL-01, but three were still not clear after 30 PUVA exposures. TL-01 achieved clearance/MRA a median of 11 (6.5-25; P = 0.001) days more quickly than PUVA, but required a median of 24.5 compared with 19 exposures [95% confidence interval (CI) for difference 1.5-5.5; P = 0.01]. Ten patients were withdrawn (four because of inadequate response of PUVA-treated halves). Analysed on an intention-to-treat basis, 21 of 28 (75%) of all participants reached clearance/MRA with TL-01 compared with 15 of 28 (54%) with PUVA (95% CI for difference 4-37%; P = 0.03). Remission durations did not differ. CONCLUSIONS: When administered according to these regimens in a skin phototype I-III population, TL-01 UVB is more efficacious than TMP bath-PUVA in the treatment of chronic plaque psoriasis.