Cutaneous

T cell lymphoma
 Epidemiology
 Incidence rate: 0.3 / 100,000 person-years
 Race: highest in blacks, lowest in Asians
 Male: Female = 2:1
 Mortality rate: 0.064 / 100,000 person-years
 Highest in blacks
 Lowest in Asians

 Surviving > 11 years after diagnosis: unlikely

die from MF
 Prognosis
 Age and Black race: poorer prognosis
 LAP not indicate poorer long-term outco
me?
 In generalized patches, plaques MF(T2):
24% disease progression, 20% die of dav
anced disease
 10-year survival rate
 T2: 67.4%
 T3: 39.2%
 T4: 41%
 Etiology
 A disease of chronic antigen stimulation i
n epidermis  T cell proliferation  mali
gnant clone
 HTLV-1? : only associated with adult T cell
leukemia/lymphoma
 EBV? : not yet proven
 S. aureus superantigen enterotoxin?, toxic
shock toxin-1? : stimulation of clonal expa
nsion
 Chemical exposure?: no correlation found
 Pathophysiology
 CTCL: skin-homing T cells with unique surfac
e receptor: CLA (cutaneous lymphocyte-associ
ated antigen)
 Course:
 T cell circulating high endothelial venules  respo
nd to unknown signals from epidermis  tethering
and rolling on P-selectin and E-selectin  extravas
ating into inflamed skin
 Unique feature:
 T cell clonal population
 Modulated antitumor response
 Epidermal microenvironment
 T cell clonal population
 CLA expressed on memory T cells home to s
kin by binding to E-selectin on vascular end
othelial cells, and superinduced during cuta
neous inflammation
 CLA: cell surface glycoprotein, an inducible
carbohydrate modification of PSGL-1 ligand;
binding to E-selectin
 < 20% of peripheral T cell express CLA
 CLA can be induced in all peripheral blood T
cell
Modulated antitumor respo
nse
 Responding pt: lower CD4/CD8, higher
CD8+ T cells
 CD8+ T cells: antitumor response
 Fas/FasL  apoptosis of cells
 Strong Fas expression in early disease
 loss of Fas in advanced MF
 Epidermal microenvironment
 Epidermis is a microenvironment for m
alignant cells
 ↑IL-5, IL-4 mRNA, Th2 cytokines
 ↓IFN-γ
 IL-7: by keratinocyte, T cell growth facto
r
 IL-15: growth-stimulating cytokine for B
and T cells, potent T cell chemoattracta
nt
Oncogene/tumor-suppresor ge
nes?
 Loss of heterozygosity(LOH)
 45% of MF
 67% of Sezary syndrome

 Possible genes
 All stage: LOH 1p, 9p  tumor-suppressor
genes p73, TAL1, p15, p16
 Advanced disease: LOH 17p, 10q  Fas, P
TEN, p53
 Clinical manifestations
 CTCL
 - MF (most common)
 - Non-MF CTCL

 DD:
 - parapsoriasis
 - cutaneous pseudolymphomas

 - other systemic lymphomas with skin infi

ltrations
 Clinical features
 Begin with flat lesions (macules and patches), often
with inflammation and pruritus
  nondiagnostic patches persist for years or resolve
spontaneously
 The lymphoma's affinity for the skin persists throug
hout all but the final stages of the disease
 Invasion of the epidermis is typically associated wit
h the clinical changes of scaling and pruritus.
 As the cells proliferate, lesions become firmer and
more varied in their surface and contour (plaques)
 The clinical progression of the disease then proceed
s at variable rates by development of cutaneous nod
ules and tumors or erythroderma
Sézar
y
 Mycosis Fungoides Variants
--Patch and Plaque Stage
 Early patch stage: single or multiple, e
rythematous, scaly macules and patch
es, variable size, usually well defined,
with color of orange to a dusky violet-r
ed, and usually on unexposed sites
 Symptoms: intensely pruritic or asymp
tomatic and occasionally may be transi
tory
 Course: disappearing spontaneous
ly without scarring
 Often a preceding “chronic dermatiti
s” for 10 to 20 years, “therapeuticall
y resistant” chronic contact dermatit
is, atopic dermatitis, psoriasis, or ecz
ema
 - 77%: antecedent, noninfectious skin
conditions
 - 32%: “dermatitis, not otherwise spe
cified:
 Dermatosis refractory to the usual
modalities of treatmentl multiple b
iopsies should be taken at 3-month
intervals until a definite diagnosis
has been made
Sézar
y
Hypopigmented mycosis fun
goides
 A variant of patch or early plaque MF
 In darker-skinned pt may be the most
common presentation of MF
 Respond to therapy by re-pigmenting
 Relapse often presents as hypopigmen
tation
 Pigmented purpura
 CTCL often reveals lesions of capillariti
s
 Some patients may present with pigme
nted
purpura
 Respond to skin-directed therapy (SDT)
of CTCL
 DD: Schamberg’s disease
 Granulomatous CTCL and slack
skin
 a constellation of unique clinical and h
istologic findings that has
occurred primarily in females
 It is not infrequent that granulomatous
changes are encountered in the histolo
gy of CTCL
 At the extreme end of this spectrum: g
ranulomatous slack skin develop large
regions of slack skin accompanied by f
ibrotic bands
Pagetoid reticulosis (Woringer-K
olopp disease)
 As a chronic solitary plaque, with long
duration, slow growth, benign nature not
typical of lymphoma
 Alopecia mucinosa
 T cell infiltrative disease kno
wn as follicular mucinosis
 grouped follicular papules or
red, raised, boggy, occasional
ly nodular plaques
 In hair-bearing areas, alopeci
a may be the presenting sign
 Adnexotropic CTCL
 follicular MF: follicular-based, erythe
matous papules and alopecia
 CTCL may infiltrate eccrine: multiple s
mall papules, anhidrosis, compromise
of eccrine system
Sézar
y
 Immunophenotypic Syndromes
--Suppressor T cell lymphoma
(CD8+ lymphoma)
 at least two variants
 1. A more chronic variant: CD2
↑, CD7↓
 2. Rapidly progressive with for
mation of nodules that ulcerate,
distribution is diffuse with inv
olvement of palmar/plantar sur
faces: CD2 ↓, CD7↑
 Gamma-delta T cell lymphoma
 CD3+ and CD4+, rare CD3+CD8+
 Even more rare double-negative (CD3+, CD4
-, CD8-, can lyse target cells epidermal n
ecrosis)
 Marked epidermal necrosis progressed to ulceratio
ns after interferon therapy– case report
 Variant: deep dermal and subcutaneous infilt
rates
 lipotropic gamma-delta lymphoma invariably acco
mpanied by excesive γ-interferon production and h
emophagocytic syndrome
 Cutaneous natural killer cell
lymphoma
 NK cell: CD56+
 NK-expressing T cell lymphoma & NK
lymphoma: clinically indistinguishable
 Large granular lymphocytes, variable lesions
from erythematous papules to tumors with
ulceration, aggressive with median survival
rarely > 15 months
 Erythrodermic variants
 de novo or progression
 Clinical: diffusely bright red with apparent scaling, may
be characteristic symmetric islands of uninvolved skin; s
paring areas: folded skin, abdomen, antecubital, axilla
(deck chair or folded luggage sign) ; may be hyperkerato
sis, scaling and fissuring of palms and soles , alopecia, e
ctropion, nail dystrophy, ankle edema with shiny and
hidebound(painful)
 DD: pityriasis rubra pilaris, secondary to psoriasis, atopi
c dermatitis, seborrheic dermatitis, and drug eruption
 leonine facies DD: lepromatous leprosy, sarcoidosis, and
leishmaniasis
 Symptoms: fever, chills, weight loss, malaise, insomnia s
econdary to pruritus, and poor body temperature homeo
stasis
 Erythrodermic variants
 Erythroderma: > 80% BSA with ill-defined bor
ders
 Sezary:
 Erythrodermic
 biopsy of CTCL
 > 5%/100 lymphocytes with cerebriform nuclei(Sez
ary cells) on PB smear
 evidence of CTCL in PB (TCR+ or ↑ CD4/CD8 ratio)
 Sezary pt died from infectious complications,
not from progressive disease
 CTCL tumors
- Mycosis fungoides tumors
 tumor stage may occur anywhere, but have a predil
ection for
the face and body folds: axillae, groin, antecubital f
ossae, and, in women,
the inframammary area
 De novo occurrence suggests metastatic spread by c
ells of a malignant T cell clone
 The nodules are reddish brown or purplish red and
smooth-surfaced but will often ulcerate and may be
come secondarily infected
 DD: B cell leukemia/lymphoma, carcinoma cutis, sa
rcoidosis, infection (deep fungi, atypical mycobacte
ria, leprosy)
 Non-MF CTCL tumors
 If tumor stage mycosis fungoides is the initial pre
sentation of the disease, the patient is often
referred to as having the tumeur d'emblee variant
 Tumors of patients without a previous history or
histologic features of mycosis fungoides are best
termed non-mycosis fungoides CTCL tumor
 Cellular morphology subdivided into large, small,
and pleomorphic categories
 Angiotropism, CD30 expression are also
recorded in the characterization of a non-mycosi
s fungoides CTCL
 CD30+ (Ki-1) LYMPHOMA
VS. CD30- LYMPHOMA
 Typical clinical appearance: tumor stage lesio
n with central ulceration
 CD30+ lymphomas having a better prognosis t
han CD30- lymphomas
 Feature of CD30+ lymphomas is a tendency to
spontaneous resolution, also a tendency to pro
gress to aggressive malignant lymphoma
 Tx: Aggressive radiotherapy with or without fo
llow-up chemotherapy is recommended
 Follow-up studies suggest that systemic polyc
hemotherapy as initial treatment does not res
ult in higher cure rates or less relapses when c
ompared to local ablative therapy
 Small Cell vs. Large Cell
vs. Pleomorphic T Cell Cutaneo
us
Lymphoma
 histologically separable from other cut
histologically separable from other cut
aneous T cell lymphomas
 The degree of cellular atypia should be
recorded at the time of diagnosis and r
elapse
Angiocentric Cutaneous T Cell L
ymphoma
 malignant angioendotheliomatosis
 progressive, fatal condition and begins typicall
y with
reddish-brown patches of plaques, frequently
on the head, and there may be progression to a
ggressive central nervous system involvement
 histology demonstrates atypical cells inside blo
od vessels
 With immunoperoxidase studies, it was demon
strated that this is a cutaneous lymphoma with
an endothelial-tropic cell
Subcutaneous (lipotropic, pan
niculotropic) CTCL
 The most aggressive variant, the worst prognosis
 Typically as de novo lesion
 Inflammatory nodules, uncommon ulcerations
 Distinct features:
 Malignant cell frequently express γδT cell receptor
 Cells often induce variable degrees of hemophagocytic
syndrome
 frequently accompanied by anemia, thrombocytopenia,
granulocytopenia in hemophagocytic syndrome
Dual Lymphoid Neoplasia of the
Skin
 collection of syndromes characterized by com
bined B cell
and T cell lymphoproliferative disorders with
skin lesions
 Hypothesis:
 increased risk of second malignancies in CTCL pati
ents
 chronic B cell stimulation from malignant
TH2 helper T cells selecting out a clonal proliferati
on of B cells, which become malignant. Possibly th
ere is a lymphoma-suppressor gene that
allows both B- and T-derived cells to become unreg
ulatable
Patient assessment
 Prognostic factors
 Tumor burden: skin, lymph nodes, periph
eral blood; also for follow-up
 Degree of atypia
 Immunocompetence of patient

 “anaplastic nature”: degree of transform

ation of malignant cell poor prognosis
 “The worse the skin, the worse the progn
osis.”
 Skin evaluation Lymph nodes Peripheral blood

Identity of the Immunogenotyping best d Early: lymphadenopathy, reactive Hematogeneously spreading

malignant one with PCR hyperplasia germinal follicl Lymphocyte recirculating path
cell Do PCR at diagnosis 1 e size↑, proliferation of histioc way model: skin←→LN←
population 5% PCR(-) yte containing lipids, melanin, →vascular system
Preference of malignant c hemosiderin PCR (for TCR rearrangement)
ells for epidermis, dil Atypical lymphoid cells: deeply in : detect clonal T cells
ution in reactive infiltr dented cuclei (cerebriform), s No changing staging
ate in dermis cant cytoplasm, in paracortic Currently lacking quantitative
al area proliferate and effac methods for correlation
e structure
LN biopsy for:
1. confirm
2. large cell transformation
3. evaluate structure
PCR: not valuable (CTCL cells tra
fficking through LN)
Tumor patch/plaque: T1(< 10%), T2(> LN: poor prognosis Circulating CTCL often indisti
burden 10% BSA) Patho(-): nguishable from mature T
Tumor: T3 Palpable(-): N0 cell:
Erythroderma: T4 Palpable(+): N1 B0 < 5%
- study: thickness from granula Patho(+): B1 > 5%
r layer to lower limit of infilt Palpable(-): N2 Antibodies to variable sectio
rate correlate with morbi Palpable(+): N3 ns of βchain of TCR: norm
dity Best imaging: CT scan al < 5%(+) blood lymphoc
ytes
Hints of malignancy:
CD4/CD8↑
CD45RO↑(memory cell mar
ker)
CD4+CD7-↑
Approach:
Flow cytometry (CD3, CD4,
CD8, CD45RO) → CD4/C
D8↑ or CD45RO↑→ PCR
and gene rearrangement s
tudies confirmation
Atypia (poor Enlarged pale nulei, Median Survival: Sezary cell: activate
prognosis, prominent nucle - Small cells with hy d T cells
tendency oli, loss of T cell perchromatic nu Hyperchromatic and
refractory) markers clei: 40 months hyperconvolute
Immunophenotypin - Mixture: 26 month d nuclei infla
g: more abnorm s mmatory dermat
alities by immun - Larger cells with p oses, Dilantin h
operoxidase in ale nuclei: 9 mo ypersensitivity s
pt with aggressi nths yndrome
ve transformed l Poor prognosis: > 5
ymphoma % circulating cel
ls with hypercon
voluted nuclei
Count 100 lymphoc
ytes
Immunocompetence (a As disease progress: N0: good Assessing normality
ffect some therapy Fewer CD8 in tissue, prognosis by flow cytometry
responsiveness) ↑CD4/CD8 Normal T cell populat
Impairment of cutaneou ion estimated by
s immunity: yeast, ti CD8+ cells
nea, herpetic infecti
ons, tendency to de
velop cutaneous m
alignancies
Staging
 Stage I: N0
 Stage IIA: N1
 Stage IIB: T3
 Stage III: T4
 Stage IVA: N2, N3
 Stage IVB: M1
 Disease in other tissues
 Routine invasive staging procedures not indicated  surve
y organ system when suggested by history, PE, routine test
s (table 157-6)
 Widespread CTCL is commonly found at autopsy, clinical
apparent extracutaneous disease is much less
 Bone marrow uncommon clinically (30-40% positive by aut
opsy): osteolytic lesion, pathologic fractures, inflammator
y polyarthritis (involve synovium)
 Pulmonary uncommon clinically (40-60% positive by autop
sy):
 parenchymal nodule (most often): poorly marginated, usually bilat
eral
 pulmonary infiltrates: usually bilateral, symmetric, interstitial, low
er lung
 most pt have extensive and progressive extracutaneous disease
 Pathology
 Quit topical or systemic treatment for at
least 4 weeks prior to biopsy
 Classic finding: lymphocytes with hyper
chromatic, hyperconvoluted nuclei clust
ered in epidermis in microabscesses
 Classical dermal infiltrate: mononuclear
cells with deeply indented nuclei with m
ixed inflammatory cells, epidermal lym
phocytes usually larger than dermal lym
phocytes
 Pathology
 Erythroderma: perivascular accumulat
ion of lymphocytes
 Histologic feature: epidermotropism, c
ytomorphology(large cell, small cell, p
leiotropic), angiotropism, lipotropism,
CD30 expression
 Diagnosis and differential diagnosis
 Suspicion:
 skin eruption refractory to therapy
 chronic inflammatory eruption

Epidermotropic infiltrate Eczema, psoriasis, erythroderma, PRP, lichen plan

us, drug eruption, photosensitivity, pompholyx, v
itiligo, annular erythema, suborrheic dermatitis, i
ntertrigo, tinea, alopecia

Dermal infiltrate Urticaria, vasculitis, annular erythema, purpura, ins

ect bite
Subcutaneous Erythema nodosum, leg ulcer, pyoderma gangreno
sum
Guidelines for diagnosing T1, T2 MF
Major minor Negating

Morphology: poikiloderma, arcu Morphology: papulosquamous, Morphology: digitate dermatosis

ate, annular lesion with ato erythematous patch/plaque, (truncal-parallel-length >> w
phy > 4 cm alopecia, multiple > 3 cm hy idth)
popigmented patches

Distribution: bathing suit, breast Distribution: truncal, proximal/di

s, preaxillar, inguinal stal extremities

Biopsy: definite- Pautrier microa Biopsy: epidermal lymphs > der Biopsy: another dermatologic
bscess, atypical lymphocyte mal lymphs diagnosis
s Ancillary studies: PCR+ for TCR
rearrangement
 ≧2 major
 1major + 2 minor
 All 4 minor
 Treatment
 Primary goals: quality of life↑, survival↑, cure
 Tumor burden the most important marker for s
urvival
 1. remission: the first step to cure
 2. maintenance: ↓relapse, ↓therapeutic expos
ure and accumulative toxicities
 Table 157-8
 Modalities: skin-directed therapies, biological r
esponse modifiers, cytotoxic therapies, combin
ation
 Modalities

Remittive or palliative Maintenance

Uni/oligo lesion SDT None

Scattered SDT SDT

patch/plaque
Erythroderma BRM, CTX, BRM, CTX,
combination combination
Refractory Combination, CTX Combination, CTX

Tumor XRT, CTX, BRM, XRT, CTX, BRM,

combination combination
 Induction therapy
Modality Advantage or indication Toxicity
Spot XRT Most reliable/rapid Minimal acutely
(x-ray therapy) Chronic: radiation dermatitis,
cutaneous malignancy
Topical chemotherapy For limited BSA Systemic absorption: marrow sup
__carmustine(BCNU) Apply BCNU ointment at pression, check CBC q2wk
Pt compliance required night, wash off in the Dose-responsive local irritation
morning /hyperpigmentation
8-20 wk needed to clear Cumulative toxicity: structural da
lesions mage- sking thinning, telangie
ctasia

Topical retinoid < 15% BSA Dose-responsive irritation

__bexarotene Apply bexarotene 1% gel at
Pt compliance required night, 1wk later topical
bid use, adjust frequenc
y according to irritation
12-16 wk needed to clear le
sions
Disseminated patch/plaque disease
 Most commonly used modalities: phot
otherapies, topical chemotherapy, tota
l skin EBRT (electron-beam radiothera
py)
PUVA Require regular treatment Cutaneous neoplasm
Oral 8-methoxypsoralen+UVA Initial: 3-4/wk, up to 3 mo Cataract: eye protection
nths or remission 24h following PUVA,
End point: mild degree ph annual eye follow
ototoxicity
Maintenance: 1/2-4wk aft
er stable remission

UVB and NBUVB More convenient for pt Acute toxicity: phototoxicit

Patch CTCL often comple y
tely cleared Chronic toxicity: cutaneou
Less efficacy(esp plaque) s malignancy
as PUVA
Initial: 3-5/wk
Maintenance: 1/wk
Total-skin topical chemotherapy
Nitrogen mustard Initial: aqueous form 1 Delayed hypersensitivi
(mechlorethamine hyd 0mg in 50 mL wate ty reaction
rochloride) r  total BSA Irritant reation
10 mg% ointment less Cutaneous malignanc
sensitizing, more st y
able Hypo- & hyperpigment
Maintenance: daily ap ation
ply
 Total-skin radiation therapy
 Total-skin electron-beam radiation (TSEB)
 Electrons penetrate only to upper dermis
 5mm-thick contact lenses for eyelid involvement
 Nail shields prevent anonychia

 Complete remission: 80-95%

 Relapse: mostly in 1st year after completion, very rar
e after 3 years
 Relapse-free rate: 42% at 10 years for limited plaques
 Median Disease-free interval:
 > 3 years in limited plaque
 ~ 1 year for generalized plaque/erythroderma
 < 6months for tumor stage
TSEB 30 cGy(3000 rad) in 3 months /course
Second course 30 cGy (3600 rad) with
highly fractionation
Repeat course require highly fractionat
ed dose of 1 Gy/dose

small-field or spot orthovoltage radioth Total dose: 8-15 cGy(800-1500 rad)

erapy with soft x-ray Fraction: 0.75-5 cGy (75-500 rad)
(60-100kV with half-value layers of 1-.
5mm Al)
 Maintenance therapy
 once remission achieved, normal skin can be
maintained with lower doses and frequencies
of the therapies used to clear it
 maintenance therapy modalities: PUVA, total-
skin nitrogen mustard, extracorporeal photoc
hemotherapy, interferon
 most commonly used maintenance: PUVA (or
UVB)
 from experience of topical nitrogen mustard a
nd TSEB, relapse after 5-8 years of treatment
was extremely rate  malignant cutaneous T
cells recirculate without lesion for up to 5 yea
rs
 PUVA maintenance regimen:

 once/ wk x 1 year 
 once/ 2wk x 1 year 
 once/ 3wk x 1 year 
 once/ 4wk x 2 year 
 Complete treatment course
  8 years without disease  CURE!
Management of suspected rela
pse: topical glucocorticoids
 effect of aggressive topical steroid use: blunt T cell
activation process
 use in
 1. early course of CTCL
 2. Relapse of disease after remission achieved
 Regimen for treating early lesion of MF: (first line
treatment for suspected relapse)
 Class I topical steroids bid x 8 wk
 (can identify pt need to undergo 4-week wash-out before
repeated biopsy)
 Erythroderma
 Erythroderma: immune dysfunction results in total-
skin redness, scaling, discomfort
 immune-based therapies: biologic response modifie
rs (BRMs)
 1. oral retinoids
 2. IV extracorporeal photochemotherapy (ECP)
 3. subcutaneous injection of INF-α
 monotherapy or combination?
 partial responses are more common as monotherapy
 what’s the goal?
 - Goal: remission  combination therapy
 - Goal: palliation  monotherapy often sufficient (commonly
partial response)
Retinoid - 1st-generation retinoid (isotretinoi - Erythrodermic pt may have ↑desqu
therapy n) is effective amation during first few weeks
- the more CTCL-specific retinoid: - neutropenia
bexarotene (selectively binds r - hyperlipidemia/hypercholesterolemi
etinoid X receptor) a: occurred rapidly within 2-4 wk,
- other retinoids: less-specific bind with serious and reversible pancr
ing eatitis  dose reduction
- Dose: 300mg/m2 PO with eveni - central hypothyroidism: TSH and F
ng meal (average dose 450-6 T4↓within weeks, may be subtle
75mg/day) symptoms (fatigue, feeling cold),
- response: in all phase (plaque, t reversible within weeks after stop
umor, erythroderma; area↓, pr ping retinoids  supplement Lev
uritus↓) othyroxine
- improvement typically occurs by - drug interaction: gemfibrozil, warfari
WEEK 12 n
- dose-response relationship - No immunosuppression with bexaro
tene therapy
- monthly followup: lipid, liver, thyroid
Extracorporeal photochemoth Photoinactivation of pt’s lymphocytes by 8-methoxypsoralen (8-MOP)
erapy with UVA  re-infusion of these cells to pt (~ 3hr) x 2 days / ever
y 4 wk
- 1/4 complete response
- 2/4 partial response
- 1/4 no response
Improvement course:
- begin 6 wk
- after 4-6 months, typically a gradual and permanent ↓erythema, scal
ing, pruritus; return of body hair, loss of rigors, return of sweating
- partial response may ↓infectious complications
feature: when < 5% malignant lymphocyte pool photoinactivated, ther
e can be clinical responses, with > 95% malignant lymphocyte di
sappear over time
immune system-related
most immunocompetent pt respond, more normal CD8+
heavily pretreated, longer duration: less response
T3,T4: SDT(TSEB) + BRM(ECP) longer survival than TSEB group
α- Monotherapy response: Initial week: flu-like illness (fever,
interfe Complete response 10-27%, du myalgia, fatigue, listlessness)
ron ration < 6 months Long-term toxicity:
Response took 3-6 months gra - Neurologic: depression, neuropa
dually thy, dementia, myelopathy
Dose: 3 MU x 3 times /week, in - Autoimmune: proteinuria, thromb
creased to maximally tolerat ocytopenia, anemia
ed dose (~ 12MU/day)
After achieving maximal respon
se, maintenance dose: 1MU
/day
 Refractory
 Combination therapy
 Debulking treatment + BRM
 1. Interferon + PUVA  then taper interfe
ron, use PUVA as maintenance
 2. retinoid + PUVA
 Cytotoxic therapy
 CTCL cells and normal mature T cells:
same sensitivity to cytotoxic agents
 1. targeting agents: preferentially bind
actively growing T cells
 2. chronic low dose oral chemotherapy
(months to years)
 Most frequently used agents: Chloram
bucil, Methotrexate: low-dose daily
Chlorambucil Frequently combined with prednosone
Dose: chlorambucil 4 mg/day + prednisone 40 mg/day
If no hematologic toxicity + chlorambucil ↑2mg/day
Maximum response achieved prednisone tapering to 20
mg qod
Methotrexate Dose: once 20-60mg/week Refractory plaque and erythroderma be
nefited from weekly methotrexate:
palliation (complete response rare)

Denileukin diftitox (D A fusion protein - Infusion-related fever, chills slow inf

D) Targeting specific receptors of CTCL cells: minimizing da usion, add premedications
mage to normal cells - Reversible elevalation of liver enzyme
- Cytotoxic action: diphtheria toxin s, peak during the week after infusi
- cell-targeting ability: IL-2, selectively damage CTCL cells on return to normal before 2nd inf
Indication: persistent or recurrent CTCL usion, lower levels in subsequent e
Dose: 9 or 18 ug/kg/day IV 20min qd x 5 days / every 3 w pisode (risk: cachexia, hypoalbumi
eeks nemia, hepatic abnormalities)
>> for CD25+(IL-2 receptor component) pt: response rate - vascular leak syndrome edema
30% (10% complete remission) The most common grade IV toxicity
Advanced disease (> stage IIB) require higher dose Follow up daily BW
Median time to response: 6 wk
After 3 cycles of therapy, responders will be evident
Gemcitabine Dose: 1.2 g/m2 IV 30min x 3 doses/ month Mild hematologic toxicity
50% palliative response No nausea/vomiting
Multiagent chemother Response rate up to 85%, variable duration
apy CHOP
No regimen was curative for advanced disease
Tumors of CTCL:
- initial: radiotherapy by TSEB (high response rate)
- cytotoxic therapy: DD infusion (for dubulking without co
mpromising immune status) if no response CHO
P or gemcitabine
- after complete response: maintenance with nitrogen mus
tard, ECP, interferon, PUVA