Table of Contents
1
UI - 11573857
AU - Wong SF
TI -
Oral bexarotene in the treatment of cutaneous T-cell lymphoma.
SO - Ann Pharmacother 2001 Sep;35(9):1056-65
AD - College of Pharmacy, Western University of Health Sciences, Irvine, CA,
USA. siuwong@westernu.edu
OBJECTIVE: To review the preclinical and clinical information related to
oral bexarotene approved by the Food and Drug Administration for the
treatment of cutaneous manifestations of cutaneous T-cell lymphoma
(CTCL) in patients who are refractory to at least one prior systemic
therapy. DATA SOURCES: Literature accessed through MEDLINE (from 1990 to
bexarotene, Targretin, LGD1069, and cutaneous T-cell lymphoma. DATA
SYNTHESIS: The management of CTCL remains controversial due to its
rarity in the US and its heterogeneity. An evaluation focusing on the
pharmacology of bexarotene and its role in the management of the
different stages of CTCL was conducted. CONCLUSIONS: Bexarotene has
demonstrated activity in the treatment of CTCL. The oral route of
administration and the adverse effect profile of bexarotene appear to
make this drug a favorable option for the treatment of CTCL. Compared
with other systemic therapies. Phase III randomized studies are needed
to determine the clinical benefits of bexarotene as monotherapy or
combination therapy in the treatment of CTCL.
2
UI - 11790166
AU - Stevens SR; Ke MS; Parry EJ; Mark J; Cooper KD
TI -
Quantifying skin disease burden in mycosis fungoides-type cutaneous
T-cell lymphomas: the severity-weighted assessment tool (SWAT).
SO - Arch Dermatol 2002 Jan;138(1):42-8
AD - Department of Dermatology, University Hospitals of Cleveland, Case
Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106-5028,
USA. srs@po.cwru.edu
OBJECTIVE: To develop a quantitative tool to assess severity of mycosis
fungoides. DESIGN: Prospective analysis of a cohort. SETTING: University
department of dermatology-based cutaneous lymphoma clinic. PATIENTS:
From 1984 to 1995, 1186 visits from 323 referred patients seen in a
multidisciplinary cutaneous lymphoma program. MAIN OUTCOME MEASURES:
Severity-weighted assessment tool (SWAT) scores were obtained for
patients at each visit. This score represents the product of the
percentage total body surface area (%TBSA) involvement of each lesion
type (patch, plaque, and tumor or ulceration), multiplied by a weighting
factor: SWAT = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer
%TBSA x 3). In addition, the standard measurements of TBSA involvement
and physician global assessments were recorded for comparison. RESULTS:
The SWAT score correlated well with %TBSA (r = 0.95, P<.001), physician
global assessment (r = 0.60, P<.001), and time to complete remission
during psoralen-UV-A therapy (r = 0.80, P<.001), therefore indicating
validity against standard measures. Analysis of individual and subsets
of patients demonstrated that the SWAT score more accurately quantified
changes in skin disease burden, including mixed responses to treatment,
than did %TBSA alone. CONCLUSIONS: The SWAT score is a useful clinical
measurement for mycosis fungoides. The SWAT score captures overall
physician impressions of disease status on a continuous dimensionless
numerical scale, therefore providing a defined, objective, and sensitive
quantitative measure. This tool is suitable for individual patient
assessment, clinical trials, and outcome comparisons.
3
UI - 11705358
AU - Apisarnthanarax N; Duvic M
TI -
Cutaneous T-cell lymphoma. New immunomodulators.
SO - Dermatol Clin 2001 Oct;19(4):737-48
AD - Division of Internal Medicine, Department of Dermatology, University of
Texas, MD Anderson Cancer Center, Houston, Texas, USA.
During the most recent decades, much knowledge has been gained
concerning the immunologic and pathologic mechanisms of CTCL. The
development of immunomodulators aimed at correcting aberrations in
immunology and cellular growth and differentiation reflects this
increased understanding. This review of the currently available
immune-response modifying drugs shows that recombinant forms of natural
cytokines and retinoids can be developed with tolerable toxicity
profiles and substantial efficacy. Although milestone drugs such as
bexarotene have been approved by the FDA- for treatment of CTCL, other
agents such as IL-12 may also have a place in treatment of the disease.
Even though unapproved, IFN-alpha may be the most active single
immunomodulating agent against CTCL. It seems that further delineation
of CTCL cytokine profile changes and immunologic aberrations are key in
developing effective immunomodulators that are able to reverse these
alterations.
4
UI - 11737522
AU - Flaig MJ; Cerroni L; Schuhmann K; Bertsch HP; Kind P; Kaudewitz P;
TI -
Sander CA
Follicular mycosis fungoides. A histopathologic analysis of nine cases.
SO - J Cutan Pathol 2001 Nov;28(10):525-30
AD - Department of Dermatology, LMU, Munich, Germany.
BACKGROUND: The spectrum of mycosis fungoides is exceedingly broad. Many
different variants have been described, based on both clinical
appearance and histological pattern. A rare form which shows
preferential infiltration of hair follicles by malignant lymphocytes is
follicular mycosis fungoides. METHODS: We reviewed our experience with
nine cases of follicular mycosis fungoides. RESULTS: The unifying
feature was infiltration of the hair follicle epithelium by atypical
lymphocytes causing varying degrees of damage to the hair follicles. In
some specimens the lymphocytes displayed only minor atypia leading to a
misinterpretation as pseudolymphoma. Gene rearrangement studies were
particularly helpful for establishing a diagnosis of malignant lymphoma.
Additionally, epidermotropism of lymphocytes, eosinophils and mucin
deposition were present to varying degrees. Mucin makes the distinction
from mycosis fungoides-associated follicular mucinosis difficult. We
found both dermal mucin and a follicular mucinosis pattern present at
different stages of disease in the same patient. CONCLUSIONS: We suggest
the term mycosis fungoides-associated follicular mucinosis should be
replaced by follicular mycosis fungoides in future lymphoma
classification schemes.
5
UI - 11807795
AU - Haffner AC; Tassis A; Zepter K; Storz M; Tureci O; Burg G; Nestle FO
TI -
Expression of cancer/testis antigens in cutaneous T cell lymphomas.
SO - Int J Cancer 2002 Feb 10;97(5):668-70
AD - Department of Dermatology, University Hospital of Zurich, Zurich,
Switzerland.
Cancer/testis-antigens (CTA), a novel and expanding family of
immunogenic proteins detected by serological screening of recombinant
cDNA expression libraries, encompass promising candidate targets for
T-cell based immunotherapy. We screened kryo-preserved tissue of
cutaneous T cell lymphoma (CTCL, n=36) such as mycosis fungoides (MF,
n=17), pleomorphic cutaneous T-cell lymphoma (n=8) and Sezary's syndrome
(SS, n= 11) as well as a non-malignant entity (small plaques
parapsoriasis, SPP, n=5), for the expression of CTA by RT-PCR and
Northern blot hybridization. From a panel of eleven CTA (MAGE-1,
MAGE-C1, MAGE-3, BAGE, GAGE, SSX-1, SSX-2, SSX4, SCP-1, NY-ESO-1 and
TS85) (HOM-Tes-85), mRNA expression could be detected for SCP-1 in 8/17
MF and 6/8 pleomorphic CTCL patients but was completely absent in small
plaques parapsoriasis. SS patients had a more heterogeneous antigen
expression pattern: Gage (1/11), MAGE-1 (3/11), MAGE-3 (6/11), MAGE-C1
(5/11), NY-ESO-1 (7/11) and TS85 (5/11), with expression of MAGE-3
confirmed by immunohistochemistry. CTA could provide defined targets for
antigen-based vaccination in a high percentage of cases with CTCL. SCP-1
might serve as an additional diagnostic indicator in early and
clinically indistinct lesions suspicious for cutaneous T-cell lymphoma.
Copyright 2001 Wiley-Liss, Inc.
6
UI - 11707823
AU - Duvic M; Feasel AM; Schwartz CA; Cather JC
TI -
Enterococcal eschars in cutaneous T-cell lymphoma tumors: a distinct
clinical entity.
SO - Clin Lymphoma 2000 Sep;1(2):141-5
AD - Section of Dermatology, Division of Internal Medicine Specialties, M.D.
Anderson Cancer Center, Houston, TX 77005, USA. mduvic@mdanderson.org
Cutaneous T-cell lymphomas (CTCL) are extranodal non-Hodgkin's T-cell
lymphomas that present in the skin, the most common form being mycosis
fungoides. The progression of disease is associated with acquired
immunodeficiency and increased susceptibility to infections. Ten CTCL
patients presented with dark brown to black eschars overlying ulcerated
tumors that cultured positive for Enterococcus and healed with
appropriate antibiotic therapy. Enterococcal infections in CTCL tumors
may be recognized as a distinct clinical entity requiring specific
intervention.
7
UI - 11756953
AU - Vonderheid EC; Bernengo MG; Burg G; Duvic M; Heald P; Laroche L; Olsen
TI -
E; Pittelkow M; Russell-Jones R; Takigawa M; Willemze R; ISCL
Update on erythrodermic cutaneous T-cell lymphoma: report of the
International Society for Cutaneous Lymphomas.
SO - J Am Acad Dermatol 2002 Jan;46(1):95-106
AD - MCP Hahnemann University, Philadelphia, Pennsylvannia 19102, USA.
vonder@erols.com
Two conferences were sponsored by the International Society for
Cutaneous Lymphomas (ISCL) to gain consensus on definitions and
terminology for clinical use in erythrodermic cutaneous T-cell lymphoma
(E-CTCL). Three subsets of E-CTCL were defined: Sezary syndrome
("leukemic phase" E-CTCL), erythrodermic mycosis fungoides (secondary
E-CTCL that develops in patients with mycosis fungoides), and E-CTCL,
not otherwise defined. The hematologic criteria recommended for Sezary
syndrome are intended to identify patients with a worse prognosis
compared with the other E-CTCL subsets and consist of one or more of the
following: (1) an absolute Sezary cell count of 1000 cells/mm3 or more;
(2) a CD4/CD8 ratio of 10 or higher caused by an increase in circulating
T cells and/or an aberrant loss or expression of pan-T cell markers by
flow cytometry; (3) increased lymphocyte counts with evidence of a
T-cell clone in the blood by the Southern blot or polymerase chain
reaction technique; or (4) a chromosomally abnormal T-cell clone. For
staging purposes, it is proposed that these criteria define the B2 blood
rating and that the B2 rating be considered equivalent to nodal
involvement.
8
UI - 11781245
AU - Urosevic M; Willers J; Mueller B; Kempf W; Burg G; Dummer R
TI -
HLA-G protein up-regulation in primary cutaneous lymphomas is associated
with interleukin-10 expression in large cell T-cell lymphomas and
indolent B-cell lymphomas.
SO - Blood 2002 Jan 15;99(2):609-17
AD - Department of Dermatology, University Hospital Zurich, Switzerland.
Primary cutaneous lymphomas (CLs) constitute a spectrum of diseases
characterized by a clonal accumulation of lymphocytes in the skin. Most
CLs display a T(h)2 cytokine profile, including expression of
interleukin-10 (IL-10). Because the up-regulation of HLA-G, a
nonclassical class Ib molecule inducible by IL-10, might account for the
immunescape of the malignant clone, HLA-G and IL-10 expression has been
investigated in 45 cases of primary CL (10 of B-cell and 35 of T-cell
origin) with quantitative polymerase chain reaction (PCR) and
immunohistochemistry. HLA-G message was present in all cutaneous B-cell
(CBCL) and T-cell (CTCL) lymphomas evaluated. Immunohistochemistry
revealed HLA-G protein expression in 23 (51%) of 45 cases (7 of 10 CBCL,
16 of 35 CTCL). While in CBCL mostly indolent types displayed HLA-G
positivity, in CTCL HLA-G expression was associated with high-grade
histology and advanced stage of the disease. Except for neoplastic and
infiltrating lymphocytes, other cells such as macrophages and dendritic
cells showed HLA-G immunoreactivity. Furthermore, IL-10 protein
expression was demonstrated in 16 (73%) of 22 HLA-G(+) cases, which
correlated with HLA-G protein presence (P <.001). HLA-G up-regulation
together with IL-10 expression in CL might additionally contribute to
the evasion of immunosurveillance and facilitate the transition from
low- to high-grade lymphomas.
9
UI - 11569930
AU - Chuang SS; Huang W; Lin CN; Chio CC; Tsai TC; Li CY; Shen CH
TI -
Primary cerebral anaplastic large cell lymphoma containing abundant
reactive histiocytes and eosinophils. A case report and literature
review.
SO - Pathol Res Pract 2001;197(9):647-52
AD - Department of Pathology, Chi-Mei Foundation Hospital, Yung Kang City,
Tainan County, Taiwan. ssc6061@ms16.hinet.net
Primary cerebral anaplastic large cell lymphoma (ALCL) is very rare. We
report on our experience with such a case and review the literature. A
46-year-old Taiwanese woman presented with headache, weakness of her
right extremity, and limited eye movement. A solid mass (5 cm x 4 cm) at
the left occipital lobe was almost completely removed. The neoplastic
cells, some of which had reniform or embryo-like nuclei, were large and
were admixed with abundant eosinophils, histiocytes, and some small
lymphocytes. These neoplastic cells expressed CD30, CD43, granzyme B and
T-cell intracellular antigen-1, but not ALK1, CD3, CD20, CD45, CD79a,
cytokeratin, and EMA. They were positive for Epstein-Barr virus-encoded
mRNA by in situ hybridization. Polymerase chain reaction study of
formalin-fixed tissue showed a clonal gene arrangement of the T-cell
receptor-gamma chain. ALCL of T-cell lineage with cytotoxic phenotype
was diagnosed. The patient received cranial irradiation and has remained
with no evidence of disease for 25 months of follow-up.
10
UI - 11794895
AU - Guilloton L; Drouet A; Estival JL; Saint Pierre G; Dupin M; Ribot C
TI -
[Transformation of mycosis fungoides to pleomorphic T-cell lymphoma and
central nervous system involvement]
SO - Rev Med Interne 2001 Dec;22(12):1244-7
AD - Service de neurologie, hopital d'instruction des armees Desgenettes,
108, boulevard Pinel, 69275 Lyon, France. laurent
guilloton@santesurf.com
INTRODUCTION: Although mycosis fungoides is a malignant T-cell lymphoma
involving mainly the skin, neurological complications are possible, with
a poor prognosis. EXEGESIS: A 59-year-old man, treated for mycosis
fungoides with transformation to a pleomorphic T-cell lymphoma for 1
year, was seen for mental status changes with confusion. A brain
parenchyma localisation was found. CONCLUSION: This observation
emphasizes the exceptional neurological tropism in the patients with
mycosis fungoides. A transformation to a more aggressive cutaneous
T-cell lymphoma seems necessary to induce a central nervous system
involvement.
11
UI - 11838656
AU - Bouwhuis SA; Markovic SN; McEvoy MT; Pittelkow MR
TI -
Extracorporeal photopheresis and adjuvant aerosolized
granulocyte-macrophage colony-stimulating factor for Sezary syndrome.
SO - Mayo Clin Proc 2002 Feb;77(2):197-200
AD - Department of Dermatology, Mayo Clinic, Rochester, Minn 55905, USA.
Encouraged by preliminary phase 1 studies of aerosolized
granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim)
in the treatment of patients with melanoma and other malignancies, we
treated a 72-year-old patient with Sezary syndrome, using alternate-week
cycles of aerosolized GM-CSF in combination with monthly cycles of
extracorporeal photopheresis (ECP). Sezary syndrome, one of the more
aggressive forms of cutaneous T-cell lymphoma, is a devastating and
highly symptomatic form of non-Hodgkin lymphoma in which malignant
clones of mature helper CD4 T cells, containing large, convoluted nuclei
known as Sezary cells, circulate in the blood and infiltrate skin.
Extracorporeal photopheresis, an immunomodulatory therapy, has become a
primary treatment for patients with Sezary syndrome. This pheresis-based
therapy combines psoralen and ultraviolet A radiation as systemic
photochemotherapy to induce immune responses. However, the activity and
efficacy of ECP vary considerably. To our knowledge this is the first
patient with Sezary syndrome treated with adjuvant aerosolized GM-CSF
combined with ECP. It produced clinical improvement and decreased the
number of circulating Sezary cells in a previously ECP-refractory
patient.
12
UI - 11807452
AU - Omura GA
TI -
Darier, Pautrier, and the "microabscesses" of mycosis fungoides.
SO - J Am Acad Dermatol 2002 Feb;46(2):320-1
13
UI - 10607318
AU - Wollina U; Graefe T; Karte K
TI -
Treatment of relapsing or recalcitrant cutaneous T-cell lymphoma with
pegylated liposomal doxorubicin.
SO - J Am Acad Dermatol 2000 Jan;42(1 Pt 1):40-6
AD - Department of Dermatology, Friedrich-Schiller-University, Germany.
BACKGROUND: Pegylated liposomes are stable, long-circulating carriers
useful for delivering doxorubicin to tumor sites with a lower toxicity
than the free drug. Free doxorubicin is used in several treatment
protocols for non-Hodgkin's lymphoma. Although pegylated liposomal
doxorubicin is currently used in the treatment of Kaposi's sarcoma, no
data are available for tumors, such as primary cutaneous T-cell
lymphomas (CTCLs). OBJECTIVE: Our purpose was to determine the efficacy
and toxicity of pegylated liposomal doxorubicin in patients with
relapsing or recalcitrant CTCL. The cumulative dose was limited to 320
mg. METHODS: A prospective pilot study was performed. Six patients (1
woman and 5 men) aged 59 to 78 years with relapsing or recalcitrant CTCL
of the mycosis fungoides type, stage (Ib/IIb), were treated with
pegylated liposomal doxorubicin to induce a clinical response. The drug
was administered at a dosage of 20 mg m(-2) once a month. Four patients
received 8 doses, and 2 patients received 6 doses. RESULTS: The best
response was a complete response in 4 patients and a partial response in
2 patients. The final outcome was a complete response in 4, a partial
response in 1, and progressive disease in 1 patient (overall response
rate, 83%). The responders showed a decrease of lymphocytic infiltrates
and activated T lymphocytes in skin biopsy specimens. Side effects were
seen temporarily, ranging from grade 0 to grade 3. The most frequent
side effects were mild anemia and lymphopenia. There was no need of
additional therapy because of side effects. CONCLUSION: These results
indicate that patients with relapsing or recalcitrant CTCL can achieve a
high response rate with pegylated liposomal doxorubicin and that a
monthly dose is a well-tolerated regimen.
14
UI - 11148501
AU - Prince HM; Seymour JF; Ryan G; McCormack C
TI -
Pegylated liposomal doxorubicin in the treatment of cutaneous T-cell
lymphoma.
SO - J Am Acad Dermatol 2001 Jan;44(1):149-50
15
UI - 11763374
AU - Bolognia JL
TI -
Unusual leucodermas.
SO - J Eur Acad Dermatol Venereol 2001 Sep;15(5):386-7
16
UI - 11763382
AU - Erkek E; Sahin S; Atakan N; Kocagoz T; Olut A; Gokoz A
TI -
Examination of mycosis fungoides for the presence of Epstein-Barr virus
and human herpesvirus-6 by polymerase chain reaction.
SO - J Eur Acad Dermatol Venereol 2001 Sep;15(5):422-6
AD - Hacettepe University, Faculty of Medicine, Ankara, Turkey.
emelerkek@hotmail.com
BACKGROUND: The aetiology of cutaneous T-cell lymphoma (CTCL) remains
unknown despite numerous investigations. In recent years, retroviruses
and human herpesviruses have been implicated to play a causal part in
CTCL. OBJECTIVE: The aim of this study was to elucidate the possible
aetiopathogenetic role of human herpesviruses (HHV) in mycosis fungoides
(MF). METHODS: Polymerase chain reaction was used to study
formalin-fixed, paraffin-embedded lesional skin biopsies from 92
subjects with MF to evidence possible presence of Epstein-Barr virus
(EBV) and HHV-6. RESULTS: Biopsy specimens from nine subjects (9.8%)
evidenced EBV DNA, whereas all except one of the subjects (1.1%) lacked
HHV-6 DNA. CONCLUSIONS: Although these findings do not support a primary
aetiological role for EBV and HHV-6 in classical CTCL, the possibility
remains that both viruses, particularly EBV, may act as potential
cofactors in the development of CTCL.
17
UI - 11812944
AU - Jones D; Vega F; Sarris AH; Medeiros LJ
TI -
CD4-CD8-"Double-negative" cutaneous T-cell lymphomas share common
histologic features and an aggressive clinical course.
SO - Am J Surg Pathol 2002 Feb;26(2):225-31
AD - Division of Pathology and Laboratory Medicine, Department of Lymphoma,
University of Texas-M.D. Anderson Cancer Center, 1515 Holcombe Blvd.,
Houston, TX 77030, U.S.A. dajones@mdanderson.org
We report 15 patients with CD4-CD8-"double-negative" T-cell lymphoma
arising in skin. There were seven women and eight men with a mean age at
diagnosis of 53 years (range 19-77 years). All but two patients
presented with solitary or multiple cutaneous nodule(s). Initial and
recurrent biopsy specimens showed a dense infiltrate centered in the
mid-dermis (extending into subcutis when sampled) of small to
intermediate-sized lymphocytes with indistinct nucleoli and frequently
irregular nuclear contours. Periadnexal infiltration and epidermal
ulceration were present in five cases with the intraepidermal cells
being primarily reactive CD4+ T cells. All cases were negative for CD30
and terminal deoxynucleotidyltransferase; one showed expression of CD56,
and six of eight tested cases were positive for T-cell receptor-delta
expression. Despite systemic chemotherapy, all 12 patients with clinical
follow-up showed recurrent or progressive disease with widespread
cutaneous dissemination in 10 of 12. Eventual dissemination to lymph
nodes or bone marrow occurred in two patients each, with at least nine
patients dead of disease or treatment complications. Only two patients
achieved lasting clinical remission (with 2'-deoxycoformycin/pentostatin
and nelarabine, respectively). CD4-CD8-"double-negative" CTCL has
distinctive histologic features and cytomorphology with a marked
propensity for rapid multifocal cutaneous dissemination.
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