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.
This article has been cited by other articles:
Maeda, A., Schwarz, A., Bullinger, A., Morita, A., Peritt, D., Schwarz, T.
(2008). Experimental Extracorporeal Photopheresis Inhibits the Sensitization and Effector Phases of Contact Hypersensitivity via Two Mechanisms: Generation of IL-10 and Induction of Regulatory T Cells. J. Immunol.
181: 5956-5962
[Abstract][Full Text]
Olsen, E., Vonderheid, E., Pimpinelli, N., Willemze, R., Kim, Y., Knobler, R., Zackheim, H., Duvic, M., Estrach, T., Lamberg, S., Wood, G., Dummer, R., Ranki, A., Burg, G., Heald, P., Pittelkow, M., Bernengo, M.-G., Sterry, W., Laroche, L., Trautinger, F., Whittaker, S., for the ISCL/EORTC,
(2007). Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood
110: 1713-1722
[Abstract][Full Text]
Bernengo, M. G., Quaglino, P., Comessatti, A., Ortoncelli, M., Novelli, M., Lisa, F., Fierro, M. T.
(2007). Low-dose intermittent alemtuzumab in the treatment of Sezary syndrome: clinical and immunologic findings in 14 patients. haematol
92: 784-794
[Abstract][Full Text]
Vagace, J. M., Gervasini, G., Morais, F., Benitez, J., Alonso, N., de Argila, D., Arranz, I., Bajo, R.
(2007). Retinal Toxic Reactions Following Photopheresis. Arch Dermatol
143: 622-625
[Abstract][Full Text]
Duvic, M., Talpur, R., Ni, X., Zhang, C., Hazarika, P., Kelly, C., Chiao, J. H., Reilly, J. F., Ricker, J. L., Richon, V. M., Frankel, S. R.
(2007). Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood
109: 31-39
[Abstract][Full Text]
Rosen, S. T., Querfeld, C.
(2006). Primary Cutaneous T-Cell Lymphomas. ASH Education Book
2006: 323-330
[Abstract][Full Text]
Maeda, A., Schwarz, A., Kernebeck, K., Gross, N., Aragane, Y., Peritt, D., Schwarz, T.
(2005). Intravenous Infusion of Syngeneic Apoptotic Cells by Photopheresis Induces Antigen-Specific Regulatory T Cells. J. Immunol.
174: 5968-5976
[Abstract][Full Text]
Willemze, R., Jaffe, E. S., Burg, G., Cerroni, L., Berti, E., Swerdlow, S. H., Ralfkiaer, E., Chimenti, S., Diaz-Perez, J. L., Duncan, L. M., Grange, F., Harris, N. L., Kempf, W., Kerl, H., Kurrer, M., Knobler, R., Pimpinelli, N., Sander, C., Santucci, M., Sterry, W., Vermeer, M. H., Wechsler, J., Whittaker, S., Meijer, C. J. L. M.
(2005). WHO-EORTC classification for cutaneous lymphomas. Blood
105: 3768-3785
[Abstract][Full Text]
von Weymarn, L. B., Zhang, Q.-Y., Ding, X., Hollenberg, P. F.
(2005). Effects of 8-methoxypsoralen on cytochrome P450 2A13. Carcinogenesis
26: 621-629
[Abstract][Full Text]
Lambertini, L., Surin, K., Ton, T.-V. T., Clayton, N., Dunnick, J. K., Kim, Y., Hong, H.-H. L., Devereux, T. R., Sills, R. C.
(2005). Analysis of p53 Tumor Suppressor Gene, H-ras Protooncogene and Proliferating Cell Nuclear Antigen (PCNA) in Squamous Cell Carcinomas of HRA/Skh Mice Following Exposure to 8-Methoxypsoralen (8-MOP) and UVA Radiation (PUVA Therapy). Toxicol Pathol
33: 292-299
[Abstract][Full Text]
Ernerudh, J., Ludvigsson, J., Berlin, G., Samuelsson, U.
(2004). Effect of Photopheresis on Lymphocyte Population in Children with Newly Diagnosed Type 1 Diabetes. CVI
11: 856-861
[Abstract][Full Text]
Girardi, M., Heald, P. W., Wilson, L. D.
(2004). The Pathogenesis of Mycosis Fungoides. NEJM
350: 1978-1988
[Full Text]
Winter, D., Fiebiger, E., Meraner, P., Auer, H., Brna, C., Strohal, R., Trautinger, F., Knobler, R., Fischer, G. F., Stingl, G., Maurer, D.
(2003). Definition of TCR Epitopes for CTL-Mediated Attack of Cutaneous T Cell Lymphoma. J. Immunol.
171: 2714-2724
[Abstract][Full Text]
Seaton, E. D., Szydlo, R. M., Kanfer, E., Apperley, J. F., Russell-Jones, R.
(2003). Influence of extracorporeal photopheresis on clinical and laboratory parameters in chronic graft-versus-host disease and analysis of predictors of response. Blood
102: 1217-1223
[Abstract][Full Text]
Ferenczi, K., Yawalkar, N., Jones, D., Kupper, T. S.
(2003). Monitoring the Decrease of Circulating Malignant T Cells in Cutaneous T-Cell Lymphoma During Photopheresis and Interferon Therapy. Arch Dermatol
139: 909-913
[Abstract][Full Text]
Lundin, J., Hagberg, H., Repp, R., Cavallin-Stahl, E., Freden, S., Juliusson, G., Rosenblad, E., Tjonnfjord, G., Wiklund, T., Osterborg, A.
(2003). Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood
101: 4267-4272
[Abstract][Full Text]
Ingen-Housz-Oro, S., Bussel, A., Flageul, B., Michel, L., Dubertret, L., Kourilsky, P., Gachelin, G., Bachelez, H., Musette, P.
(2002). A prospective study on the evolution of the T-cell repertoire in patients with Sezary syndrome treated by extracorporeal photopheresis. Blood
100: 2168-2174
[Abstract][Full Text]
Suchin, K. R., Cucchiara, A. J., Gottleib, S. L., Wolfe, J. T., DeNardo, B. J., Macey, W. H., Bromley, P. G., Vittorio, C. C., Rook, A. H.
(2002). Treatment of Cutaneous T-Cell Lymphoma With Combined Immunomodulatory Therapy: A 14-Year Experience at a Single Institution. Arch Dermatol
138: 1054-1060
[Abstract][Full Text]
Bladon, J., Taylor, P.
(2002). The common pathways, but different outcomes, of apoptosis induced by extracorporeal photopheresis and in vivo chemotherapy may reinforce the important immunomodulatory effect of monocytes. Blood
99: 3071-3072
[Full Text]
Bouwhuis, S. A., Markovic, S. N., McEvoy, M. T., Pittelkow, M. R.
(2002). Extracorporeal Photopheresis and Adjuvant Aerosolized Granulocyte-Macrophage Colony-Stimulating Factor for Sezary Syndrome. Mayo Clin Proc.
77: 197-200
[Abstract]
Stevens, S. R., Ke, M. S., Parry, E. J., Mark, J., Cooper, K. D.
(2002). Quantifying Skin Disease Burden in Mycosis Fungoides-Type Cutaneous T-Cell Lymphomas: The Severity-Weighted Assessment Tool (SWAT). Arch Dermatol
138: 42-48
[Abstract][Full Text]
French, L. E., Lessin, S. R., Addya, K., Denardo, B., Margolis, D. J., Leonard, D. G. B., Rook, A. H.
(2001). Identification of Clonal T Cells in the Blood of Patients With Systemic Sclerosis: Positive Correlation With Response to Photopheresis. Arch Dermatol
137: 1309-1313
[Abstract][Full Text]
Choi, C. J., Nghiem, P.
(2001). Tacrolimus Ointment in the Treatment of Chronic Cutaneous Graft-vs-Host Disease: A Case Series of 18 Patients. Arch Dermatol
137: 1202-1206
[Abstract][Full Text]
Evans, A. V., Wood, B. P., Scarisbrick, J. J., Fraser-Andrews, E. A., Chinn, S., Dean, A., Watkins, P., Whittaker, S. J., Russell-Jones, R.
(2001). Extracorporeal photopheresis in Sezary syndrome: hematologic parameters as predictors of response. Blood
98: 1298-1301
[Abstract][Full Text]
Alcindor, T., Gorgun, G., Miller, K. B., Roberts, T. F., Sprague, K., Schenkein, D. P., Foss, F. M.
(2001). Immunomodulatory effects of extracorporeal photochemotherapy in patients with extensive chronic graft-versus-host disease. Blood
98: 1622-1625
[Abstract][Full Text]
Ludvigsson, J, Samuelsson, U, Ernerudh, J, Johansson, C, Stenhammar, L, Berlin, G
(2001). Photopheresis at onset of type 1 diabetes: a randomised, double blind, placebo controlled trial. Arch. Dis. Child.
85: 149-154
[Abstract][Full Text]
Siegel, R. S., Pandolfino, T., Guitart, J., Rosen, S., Kuzel, T. M.
(2000). Primary Cutaneous T-Cell Lymphoma: Review and Current Concepts. JCO
18: 2908-2925
[Abstract][Full Text]
Kurzrock, R., Pilat, S., Duvic, M.
(1999). Pentostatin Therapy of T-Cell Lymphomas With Cutaneous Manifestations. JCO
17: 3117-3121
[Abstract][Full Text]
Stevens, S. R., Bowen, G. M., Duvic, M., King, L. E., Knobler, R., Lim, H. W., Margolis, D., Parry, E. J., Rook, A. H., Stricklin, G. P., Suchin, K. R., Tharp, M. D., Vonderheid, E., Zic, J. A., Whittaker, S., Fraser-Andrews, E., Russell-Jones, R.
(1999). Effectiveness of Photopheresis in Sezary Syndrome. Arch Dermatol
135: 995-997
[Full Text]
Rostami, A M, Sater, R A, Bird, S J, Galetta, S, Farber, R E, Kamoun, M, Silberberg, D H, Grossman, R I, Pfohl, D
(1999). A double-blind, placebo-controlled trial of extracorporeal photopheresis in chronic progressive multiple sclerosis. Mult Scler
5: 198-203
[Abstract]
Salerno, C. T., Park, S. J., Kreykes, N. S., Kulick, D. M., Savik, K., Hertz, M. I., Bolman, R. M. III
(1999). ADJUVANT TREATMENT OF REFRACTORY LUNG TRANSPLANT REJECTION WITH EXTRACORPOREAL PHOTOPHERESIS. J. Thorac. Cardiovasc. Surg.
117: 1063-1069
[Abstract][Full Text]
Edelson, R. L., Russell-Jones, R., Whittaker, S., Fraser-Andrews, E.
(1999). Sezary Syndrome, Cutaneous T-Cell Lymphoma, and Extracorporeal Photopheresis. Arch Dermatol
135: 600-601
[Full Text]
Hofer, A., Mullegger, R., Kerl, H., Wolf, P.
(1999). Extracorporeal Photochemotherapy for the Treatment of Erythrodermic Pityriasis Rubra Pilaris. Arch Dermatol
135: 475-476
[Full Text]
(1999). An Update on Treating Cutaneous T-Cell Lymphoma. Journal Watch Dermatology
1999: 10-10
[Full Text]
Lee, B.-N., Duvic, M., Tang, C.-K., Bueso-Ramos, C., Estrov, Z., Reuben, J. M.
(1999). Dysregulated Synthesis of Intracellular Type 1 and Type 2 Cytokines by T Cells of Patients with Cutaneous T-Cell Lymphoma. CVI
6: 79-84
[Abstract][Full Text]
Barr, M. L., Meiser, B. M., Eisen, H. J., Roberts, R. F., Livi, U., Dall'Amico, R., Dorent, R., Rogers, J. G., Radovancevic, B., Taylor, D. O., Jeevanandam, V., Marboe, C. C., Franco, K. L., Ventura, H. O., Michler, R. E., Griffith, B. P., Boyce, S. W., Reichart, B., Gandjbakhch, I., The Photopheresis Transplantation Study Group,
(1998). Photopheresis for the Prevention of Rejection in Cardiac Transplantation. NEJM
339: 1744-1751
[Abstract][Full Text]
Fraser-Andrews, E., Seed, P., Whittaker, S., Russell-Jones, R.
(1998). Extracorporeal Photopheresis in Sezary Syndrome: No Significant Effect in the Survival of 44 Patients With a Peripheral Blood T-Cell Clone. Arch Dermatol
134: 1001-1005
[Abstract][Full Text]
Koenigs, L. L., Peter, R. M., Thompson, S. J., Rettie, A. E., Trager, W. F.
(1997). Mechanism-Based Inactivation of Human Liver Cytochrome P450 2A6 by 8-Methoxypsoralen. Drug Metab. Dispos.
25: 1407-1415
[Abstract][Full Text]
HOLBROOK, M R, POWELL, R J
(1997). Is there a future for extracorporeal photochemotherapy in the treatment of the rheumatological diseases?. Ann Rheum Dis
56: 339-340
[Full Text]
Pineda, A. A., Vamvakas, E. C.
(1997). Applications of Therapeutic Apheresis in Patients with Malignant Disease. The Oncologist
2: 94-103
[Abstract][Full Text]
Slovis, B. S., Loyd, J. E., King, L. E.
(1995). Photopheresis for Chronic Rejection of Lung Allografts. NEJM
332: 962-962
[Full Text]
Licata, A. G., Wilson, L. D., Braverman, I. M., Feldman, A. M., Kacinski, B. M.
(1995). Malignant Melanoma and Other Second Cutaneous Malignancies in Cutaneous T-Cell Lymphoma: The Influence of Additional Therapy After Total Skin Electron Beam Radiation. Arch Dermatol
131: 432-435
[Abstract]
Smith, N, Spittle, M
(1994). Cutaneous T cell lymphomas. BMJ
308: 1303-1303
[Full Text]
Goldman, B. D., Oh, S.-K., Davis, B. E., Kadin, M. E., Poiesz, B. J., Koh, H. K.
(1993). Serum Soluble Interleukin 2 Receptor Levels in Erythrodermic Cutaneous T-Cell Lymphoma Correlate With Response to Photopheresis-Based Treatment. Arch Dermatol
129: 1166-1170
[Abstract]
Rook, A. H., Vowels, B. R., Jaworsky, C., Singh, A., Lessin, S. R.
(1993). The Immunopathogenesis of Cutaneous T-Cell Lymphoma: Abnormal Cytokine Production by Sezary T Cells. Arch Dermatol
129: 486-489
[Abstract]
Dover, J. S., Arndt, K. A.
(1992). Dermatology. JAMA
268: 342-344
[Abstract]
Rook, A. H., Freundlich, B., Jegasothy, B. V., Perez, M. I., Barr, W. G., Jimenez, S. A., Rietschel, R. L., Wintroub, B., Kahaleh, M. B., Varga, J., Heald, P. W., Steen, V., Massa, M. C., Murphy, G. F., Perniciaro, C., Istfan, M., Ballas, S. K., Edelson, R. L.
(1992). Treatment of Systemic Sclerosis With Extracorporeal Photochemotherapy: Results of a Multicenter Trial. Arch Dermatol
128: 337-346
[Abstract]
Rook, A. H., Prystowsky, M. B., Cassin, M., Boufal, M., Lessin, S. R.
(1991). Combined Therapy for Sezary Syndrome With Extracorporeal Photochemotherapy and Low-Dose Interferon Alfa Therapy: Clinical, Molecular, and Immunologic Observations. Arch Dermatol
127: 1535-1540
[Abstract]
Heald, P. W., Perez, M. I., Gasparro, F. P.
(1990). Dosage Guidelines: Extracorporeal Photochemotherapy (Photopheresis). Arch Dermatol
126: 1369-1369
[Abstract]
Abrutyn, E.
(1990). Photopheresis and Human Immunodeficiency Virus (HIV) Infection: The Annals Views Preliminary Reports. ANN INTERN MED
113: 263-264
[Abstract]
Bisaccia, E., Berger, C., Klainer, A. S.
(1990). Extracorporeal Photopheresis in the Treatment of AIDS-Related Complex: A Pilot Study. ANN INTERN MED
113: 270-275
[Abstract]
Rook, A. H., Jegasothy, B. V., Heald, P., Nahass, G. T., Ditre, C., Witmer, W. K., Lazarus, G. S., Edelson, R. L.
(1990). Extracorporeal Photochemotherapy for Drug-Resistant Pemphigus Vulgaris. ANN INTERN MED
112: 303-305
[Abstract]
Nickoloff, B. J., Griffiths, C. E. M., Baadsgaard, O., Voorhees, J. J., Hanson, C. A., Cooper, K. D.
(1989). Markedly Diminished Epidermal Keratinocyte Expression of Intercellular Adhesion Molecule-1 (ICAM-1) in Sezary Syndrome. JAMA
261: 2217-2221
[Abstract]
Sausville, E. A., Eddy, J. L., Makuch, R. W., Fischmann, A. B., Schechter, G. P., Matthews, M., Glatstein, E., Ihde, D. C., Kaye, F., Veach, S. R., Phelps, R., O'Connor, T., Trepel, J. B., Cotelingam, J. D., Gazdar, A. F., Minna, J. D., Bunn, P. A. Jr.
(1988). Histopathologic Staging at Initial Diagnosis of Mycosis Fungoides and the Sezary Syndrome: Definition of Three Distinctive Prognostic Groups. ANN INTERN MED
109: 372-382
[Abstract]
Lider, O, Reshef, T, Beraud, E, Ben-Nun, A, Cohen, I.
(1988). Anti-idiotypic network induced by T cell vaccination against experimental autoimmune encephalomyelitis. Science
239: 181-183
[Abstract]
Previous
