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Review of Sezary Syndrome

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Review of Sezary Syndrome REVIEWS Sezary syndrome: Immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC) EliseA.Olsen,MD,a Alain H. Rook, MD,b John Zic, MD,c Youn Kim, MD,d PierluigiPorcu,MD,e Christiane Querfeld, MD,f Gary Wood, MD,g Marie-France Demierre, MD,h Mark Pittelkow, MD,i Lynn D. Wilson, MD, MPH,j Lauren Pinter-Brown, MD,k Ranjana Advani, MD,d Sareeta Parker, MD,l Ellen J. Kim, MD,b Jacqueline M. Junkins-Hopkins, MD,m Francine Foss, MD,j Patrick Cacchio, BS,a and Madeleine Duvic, MDn Durham, North Carolina; Philadelphia, Pennsylvania; Nashville, Tennessee; Palo Alto and Los Angeles, California; Columbus, Ohio; Chicago, Illinois;Madison,Wisconsin;Boston,Massachusetts; Rochester, Minnesota; New Haven, Connecticut; Atlanta, Georgia; Baltimore, Maryland; and Houston, Texas Sezary syndrome (SS) has a poor prognosis and few guidelines for optimizing therapy. The US Cutaneous Lymphoma Consortium, to improve clinical care of patients with SS and encourage controlled clinical trials of promising treatments, undertook a review of the published literature on therapeutic options for SS. An overview of the immunopathogenesis and standardized review of potential current treatment options for SS including metabolism, mechanism of action, overall efficacy in mycosis fungoides and SS, and common or concerning adverse effects is first discussed. The specific efficacy of each treatment for SS, both as monotherapy and combination therapy, is then reported using standardized criteria for both SS and response to therapy with the type of study defined by a modification of the US Preventive Services guidelines for evidence-based medicine. Finally, guidelines for the treatment of SS and suggestions for adjuvant treatment are noted. ( J Am Acad Dermatol 2011;64:352- 404.) Key word: Sezary syndrome. This review on Sezary syndrome is dedicated to one of the co- Millennium (I), Therakos (C). Dr Querfeld: Celgene (I), Eisai authors, Marie-France Demierre, MD, who died unexpectedly (S), Eli Lilly (I), Therakos (I, C). Dr Wood: BioCryst Pharmaceu- on April 13, 2010. Dr Demierre’s research, teaching, publica- ticals (I), Gloucester (C), Merck (RG), Therakos (C), Yaupon (I). tions, and dedication to patient care in the area of cutaneous T- Dr Demierre: Celgene (C), Eisai (I), GenMab (I), Gloucester (I, S, cell lymphoma enriched the lives of colleagues and patients AB), Merck (I, S, AB), Novartis (I), Schering (I), Therakos (I). Dr alike. Pittelkow: Gloucester (C). Dr Wilson: Merck (RG). Dr Pinter- From Duke University Medical Center, Durhama;Universityof Brown: Eisai (AB, S), GenMab (I), Merck (AB, S). Dr Parker: Pennsylvaniab; Vanderbilt University, Nashvillec;Stanford BioCryst Pharmaceuticals (I), Eisai (I), Genmab (I), Gloucester University, Palo Altod; Ohio State Universitye;Universityof (C),Merck(I).DrE.J.Kim:BioCrystPharmaceuticals(I), Chicagof; University of Wisconsing;BostonUniversity Centocor (I), Eisai (C), Eli Lilly (I), Genmab (I), Gloucester (I), School of Medicineh; Mayo Clinic, Rochesteri;YaleUniver- Ten-X (I), Yaupon (I). Dr Foss: Allos (S), Eisai (C), Gloucester sity, New Havenj; University of CaliforniaeLos Angeles (C),Merck(S).DrDuvic:Allos(I,C,AB),BioCrystPharmaceu- Medical Centerk; Emory University, Atlantal; Johns Hopkins ticals (I), Eisai (I, C), Eli Lilly (I, C), GenMab (I), Merck (C), Roche University, Baltimorem; and M.D. Anderson Cancer Center, (I, C), Therakos (I, AB), Yaupon (I). Drs Advani and Junkins- Houston.n Hopkins and Mr Cacchio have no conflicts of interest to Funding sources: None. declare. Disclosure: Abbreviations are as follows: I (investigator), C (con- Reprints not available from the authors. sultant), AB (advisory board), H (honoraria), S (speaker), RG Correspondence to: Elise A. Olsen, MD, Duke University Medical (research grant, unrestricted, fellowship, etc). Center, Box 3294, Durham, NC 27710. E-mail: olsen001@mc. Dr Olsen: BioCryst Pharmaceuticals (I, S), Eisai (I), Gloucester (C), duke.edu. Johnson & Johnson (I, C), Merck (I, C), Yaupon (I). Dr Rook: Published online December 10, 2010. GenMab (I), HyBioPharma (C), Merck (C), Therakos (C). Dr Zic: 0190-9622/$36.00 Eisai (AB), GenMab (I), Gloucester (C), Therakos (I). Dr Y. Kim: ª 2010 by the American Academy of Dermatology, Inc. Allos (I, C), BioCryst Pharmaceuticals (I), Celgene (C), Eisai doi:10.1016/j.jaad.2010.08.037 (AB),GenMab(I),Kyowa(I,C),Merck(I,AB),Seagen(C), Yaupon (I). Dr Porcu: Eisai (H), Eli Lilly (I), GenMab (I), 352 JAM ACAD DERMATOL Olsen et al 353 VOLUME 64, NUMBER 2 TABLE OF CONTENTS Diagnosis 354 Abbreviations used: Immunopathogenesis 354 APL: acute promyelocytic leukemia ATG: antithymocyte globulin Therapeutic options 356 ATRA: all-trans-retinoic acid Overview 356 BIW: twice a week Immunomodulating agents 357 CCR4: chemokine receptor 4 CDA: chlorodeoxyadenosine Interferon alfa 357 CLL: chronic lymphocytic leukemia Interferon gamma 373 CR: complete response Retinoids 374 CTCL: cutaneous T-cell lymphoma DC: dendritic cell Bexarotene (Targretin) 374 d: day Retinoic acid receptor retinoids 375 DCF: deoxycoformycin Isotretinoin (Amnesteem, Claravis, dCyk: deoxycytidine kinase ECP: extracorporeal photopheresis Sotret) 375 E-MF: erythrodermic mycosis fungoides Etretinate (Tegison)/acitretin (Soriatane) 375 EORTC: European Organization for the Research and Treatment of Cancer All-trans-retinoic acid (Vesanoid) 376 FDA: Food and Drug Administration Denileukin diftitox 376 GI: gastrointestinal Extracorporeal photopheresis 377 Gy: gray HDAC: histone deacetylase Chemotherapeutic agents 378 HSCT: hematopoietic stem cell transplantation Methotrexate 378 IC50: half maximal inhibitory concentration Purine analogs (fludarabine monophosphate, IFN: interferon IFN-a: interferon alfa 2-chlorodeoxyadenosine, and deoxycoformy- IFN-g: interferon gamma cin) 379 IL: interleukin Fludarabine 379 ISCL: International Society for Cutaneous Lymphomas 2-Chlorodeoxyadenosine (cladribine) 380 IV: intravenous Deoxycoformycin (pentostatin) 380 mAb: monoclonal antibody MDR: mean duration response Gemcitabine (Gemzar) 381 MF: mycosis fungoides Forodesine 381 MRD: median response duration Alkylating agents 382 MTX: methotrexate MU: million units Chlorambucil (Leukeran) 382 NA: not applicable Nitrogen mustard (Mustargen) 382 NBUVB: narrowband ultraviolet B Cyclophosphamide (Cytoxan) 383 NCCN: National Comprehensive Cancer Network NCI: National Cancer Institute Temozolomide (Temodar) 383 NK: natural killer Topoisomerase inhibitors 383 OR: objective response VP-16 (etoposide) 383 PB: peripheral blood PK: pharmacokinetics Pegylated liposomal doxorubicin (Doxil) 384 PNP: purine nucleoside phosphorylase Histone deacetylase inhibitors 385 PR: partial response PUVA: psoralen plus ultraviolet A Vorinostat (Zolinza) 385 qd: once daily Romidepsin 385 QLQ: quality of life questionnaire Monoclonal antibodies 386 RA: retinoic acid RAR: retinoic acid receptor Alemtuzumab (Campath-1H) 386 RR: response rate Bortezomib (Velcade) 388 RXR: retinoid 3 receptor Antithymocyte globulin (Thymoglobulin) 388 SC: Sezary cell SDF: stromal cell-derived factor Interleukin-2 (aldesleukin/Proleukin) 388 SQ: subcutaneous Multiagent chemotherapy 388 SS: Sezary syndrome Hematopoietic stem cell transplantation 389 T4: erythrodermic skin stage in MF or SS TARC: thymus and activation- regulated Adjuvant agents 389 chemokine Topical and systemic steroids 389 TCR: T-cell receptor TGF: transforming growth factor Phototherapy 390 Th: T helper Topical mechlorethamine (nitrogen mustard) 390 tiw: 3 times per week Leukapheresis 390 TNF: tumor necrosis factor Tregs: regulatory T-cells Total skin electron beam radiation 391 TSEBT: total skin electron beam therapy Antipruritic therapy 392 USCLC: US Cutaneous Lymphoma Consortium Recommendations for therapy 393 UV: ultraviolet VAS: visual analog scale Reference 394 WBC: white blood cell Table I: Monotherapies in Sezary syndrome 358 354 Olsen et al JAM ACAD DERMATOL FEBRUARY 2011 Table II: Combination therapies in Sezary lymphomatous involvement. However, the blood of syndrome 364 patients with benign inflammatory dermatoses may Table III: Allogeneic bone-marrow also show CD26 or CD7 deletion.11,12,15 In addition, transplantation 369 the correlation of the blood tumor burden by flow Table IV: Treatment recommendations for Sezary cytometry and by SC preparation is inexact and may syndrome 372 offer differing results from center to center unless a Table V: Principles of therapy for Sezary single observer or a panel of experts is used to read the syndrome 393 slides. Expansion of a clonal Abbreviations 353 T-cell population assessed by CAPSULE SUMMARY polymerase chain reaction or DIAGNOSIS Southern blotting to demon- d A review of the published literature on The origin of the term strate a dominant T-cell potential treatments of Sezary syndrome ‘‘Sezary syndrome’’ (SS) receptor (TCR) gene rear- (SS) has merit for clinical practice and dates back to a series of re- rangement in the blood, al- future clinical research. ports from 1938 to 1949 in though also not specific for 1,2 16-18 which Sezary described d Efficacy of treatments for SS, both lymphoma, provides patients who presented with monotherapy and combination therapy, supportive evidence for sig- erythroderma and very large is presented here in a standardized nificant blood involvement in abnormal cells (cellules fashion using defined criteria for both the presence of an increased monstreuses) in the blood the definition of SS and objective number
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