Treatment of Cutaneous T-Cell Lymphoma by Extracorporeal Photochemotherapy

Abstract

Systemically disseminated cutaneous T-cell lymphoma is generally resistant to chemotherapy and radiotherapy. We tested a treatment involving the extracorporeal photoactivation of biologically inert methoxsalen (8-methoxypsoralen) by ultraviolet A energy to a form that covalently cross-links DNA. After oral administration of methoxsalen, a lymphocyte-enriched blood fraction was exposed to ultraviolet A (1 to 2 J per square centimeter) and then returned to the patient. The combination of ultraviolet A and methoxsalen caused an 88 +/- 5 percent loss of viability of target lymphocytes, whereas the drug alone was inactive. Twenty-seven of 37 patients with otherwise resistant cutaneous T-cell lymphoma responded to the treatment, with an average 64 percent decrease in cutaneous involvement after 22 +/- 10 weeks (mean +/- SD). The responding group included 8 of 10 patients with lymph-node involvement, 24 of 29 with exfoliative erythroderma, and 20 of 28 whose disease was resistant to standard chemotherapy. Side effects that often occur with standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. Although the mechanism of the beneficial effect is uncertain, an immune reaction to the infused damaged cells may have restricted the activity of the abnormal T cells. This preliminary study suggests that extracorporeal photochemotherapy is a promising treatment for widespread cutaneous T-cell lymphoma.

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

“…Following oral administration of methoxsalen, a lymphocyte-enriched fraction of the patient's blood was exposed to 1-2 J/cm 2 ex vivo and then returned to the patient. 76 Twenty-seven of 37 patients with resistant CTCL responded to the treatment, with an average decrease in cutaneous involvement of 64% after a mean period 22 weeks. 76 In the study by Suchin and colleagues, 89% of a consecutive sample of 47 patients had circulating malignant T cells.…”

“…76 Twenty-seven of 37 patients with resistant CTCL responded to the treatment, with an average decrease in cutaneous involvement of 64% after a mean period 22 weeks. 76 In the study by Suchin and colleagues, 89% of a consecutive sample of 47 patients had circulating malignant T cells. 126 ECP monotherapy resulted in a 75% ORR and median survival of 66 months.…”

“…The use of ECP was first reported in 1987 by Edelson and colleagues 76 In this procedure, peripheral blood leukocytes are harvested, mixed with 8MOP, exposed to UV radiation, and then returned to the patient. 15,77 In the earlier studies, 8MOP was administered orally, but this practice has now been replaced by ex vivo admixture of 8MOP prior to UV administration.…”

“…The median time to remission was 39 months. 34 76 Reported ORRs range from 31% to 80%, with 0-25% CRs. 77 Suchin and colleagues observed a 75% ORR in a retrospective cohort study, and Gottlieb and colleagues reported a CR rate of 25% and a PR rate of 46% from a retrospective chart review of 28 patients with stage III or IV disease.…”

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Following the landmark study by Edelson and colleagues describing responses in 27 of 37 patients with erythrodermic CTCL treated with ECP, ECP was approved by the Food and Drug Administration of the USA for the treatment of CTCL and is now considered the treatment of choice in the first-line management of patients with Sé zary syndrome in many centers [309]. While responses vary between case series, overall response rates hover around 60%, with a complete response rate of 20% [310,311].…”