THERAPY

Experience with total skin electron beam therapy

in combination with extracorporeal
photopheresis in the management of patients
with erythrodermic (T4) mycosis fungoides
Lynn D. Wilson, MD, MPH,a,b Glenn W. Jones, MD, FRCP, MSc,c David Kim, MD,a
Don Rosenthal, MD, FRCP,d Inger R. Christensen, BS, RN,b Richard L. Edelson, MD,b
Peter W. Heald, MD,b and Barry M. Kacinski, MD, PhDa,b New Haven, Connecticut, and
Hamilton, Ontario

Objective: We compared the prognosis of patients with erythrodermic mycosis fungoides (MF)
administered total skin electron beam radiation (TSEB) plus neoadjuvant, concurrent, and adjuvant
extracorporeal photopheresis (ECP) with the prognosis of patients administered only TSEB. Outcomes of
clinical interest include disease-free survival (DFS), progression-free survival (PFS), overall survival (OS),
and cause-specific survival (CSS).
Methods: This study was a retrospective nonrandomized series. Between 1974 and 1997, a total of 44
patients with erythrodermic MF from the Department of Therapeutic Radiology, Yale University School of
Medicine, and the Department of Radiation Oncology, Cancer Care Ontario, Hamilton, Ontario, were
collected and analyzed as a group (Hamilton = 15, Yale = 29). These patients received TSEB consisting of
32 to 40 Gy via 4 to 6 MeV. Twenty-one patients at Yale also received ECP treatment 2 days per month for a
median of 6 months. Median age was 68 years (range, 29-82 years) at the commencement of TSEB, and 66%
were male. Seventy-three percent of patients had received other therapies before TSEB, including 75
courses that failed to control disease (n = 15 systemic therapy, 16 biologicals, and 44 topical therapies). At
TSEB, 59% had hematologic involvement (B1), 30% were stage IVA (N3), and 13% were IVB (M1). Median
follow-up was 2.2 years (range, 0.3-13.9 years) subsequent to TSEB and 3.7 years from diagnosis (range, 0.8-
16.8 years).
Results: All patients responded to TSEB within 2 months of completion, with a cutaneous complete
response rate of 73%. For the 32 complete responders the 3-year DFS was 63%. It was 49% for those 17
patients who received only TSEB compared with 81% for those 15 patients who received TSEB + ECP. Cox
regression analysis demonstrated that ECP was associated with prolonged remission (DFS multivariate P =
.024, adjusting for B1 and stage). The 2-year PFS, CSS, and OS for the TSEB group were 36%, 69%, and 63%,
respectively, compared with 66%, 100%, and 88% for the TSEB + ECP cohort. Cox regression demonstrated
that ECP was associated with CSS (multivariate P = .048, adjusting for B1 and stage). For those who
progressed, a total of 49 subsequent courses of therapy were administered (n = 20 chemotherapy, 10
biologicals, and 19 topical therapies). Thirteen patients died from MF-related causes, and 8 died from other
causes. Acute and chronic toxicities were consistent with those previously reported.
Conclusion: ECP given concurrently with, or immediately after, TSEB (32-40 Gy) significantly improves
both PFS and CSS for patients with erythrodermic MF compared with TSEB without the addition of ECP. (J
Am Acad Dermatol 2000;43:54-60.)

From the Departments of Therapeutic Radiologya and Dermatology,b
Yale University School of Medicine, New Haven, and the
Departments of Radiation Oncologyc and Dermatology,d Cancer
Care Ontario, Hamilton.
Supported in part by American Cancer Society grant (CDA 95-102).
Reprint requests: Lynn D. Wilson, MD, MPH, Department of
Therapeutic Radiology, Hunter 136, Yale University School of
Medicine, PO Box 208040, New Haven, CT 06520-8040.
Copyright 2000 by the American Academy of Dermatology, Inc.
0190-9622/2000/$12.00 + 0 16/1/105510
doi:10.1067/mjd.2000.105510

54
J AM ACAD DERMATOL
VOLUME 43, NUMBER 1, PART 1
M ycosis fungoides (MF) is a rare disorder of
CD4+ T cells primarily involving the skin
and is the most common type of lymphoid
infiltrate encompassed by the term cutaneous T-cell
lymphoma. Fewer than 5% of individuals with MF
will present with diffuse erythroderma and will
therefore be classified as having T4 disease (stage III-
IVB) on the basis of a TNM classification system.1
Often those with T4 disease have circulating abnor-
mal T cells, which is prognostically unfavorable.2
Standard therapy has not yet been clearly elucidat-
ed.3 Management has focused on palliation of signs
and symptoms, which may include infection, severe
pruritus, cutaneous discomfort, and fever.
Abbreviations used
CR: complete response
CSS: cause-specific survival
DFS: disease-free survival
ECP: extracorporeal photopheresis
MF: mycosis fungoides
OS: overall survival
PCR: polymerase chain reaction
PFS: progression-free survival
TSEB: total skin electron beam
A variety of modalities to treat T4 disease have
been explored, including total skin electron beam
(TSEB) radiation, topical mechlorethamine, systemic
chemotherapy, interferon, monoclonal antibodies,
and other investigational agents. Recently, extracor-
poreal photopheresis (ECP) has emerged as a thera-
py in the United States approved by the Food
and Drug Administration for patients with Szary
syndrome, despite the lack of randomized data.
Although complete responses (CRs) have been doc-
umented with ECP, and overall response ranges from
30% to 90%, few data are available regarding 5-year
disease-free survival (DFS) or overall survival (OS).
In our experience,3 TSEB is also effective for patients
with erythrodermic MF and provides excellent palli-
ation of symptoms. When doses of 32 Gy or more are
administered, without concomitant or adjuvant ther-
apy, a complete remission rate of 70% is expected
with a 5-year progression-free survival (PFS) of 35%.3
This is a technically complicated treatment that is
not routinely available; published data regarding its
efficacy for advanced MF is relatively scarce. Therapy
is typically given over a 9-week period and poses
logistic challenges for patients traveling from signifi-
cant distances.
At Yale, patients with erythrodermic MF have
often been treated with a combination of TSEB and
Wilson et al 55
ECP, with the continuation of ECP after completion
of radiotherapy. Patients from Hamilton have not
been treated with ECP but have received TSEB with
similar doses and technique to those managed at
Yale; hence this series represents a pooled database.
This affords the opportunity to compare clinical
results with and without ECP. This report documents
the response rates, DFS, PFS, and OS for patients
managed with optimum TSEB (32-40 Gy and 4-6
MeV) in comparison to those treated with a combi-
nation of similar TSEB and ECP.
MATERIAL AND METHODS
Patient population
We reviewed our combined experience (Yale/
Hamilton) in the treatment of 44 patients with ery-
throdermic MF. Hence the series represents a retro-
spective review of such patients, the therapy they
received, and their outcomes. Between 1974 and
1997, a total of 44 patients (Yale = 29, Hamilton =
15) received optimum TSEB. Optimum TSEB is
defined as a total skin dose of 32 to 40 Gy with 4 to
6 MeV.3 All patients received a clinical interview and
comprehensive physical examination, routine blood
work, evaluation of blood for circulating abnormal T
cells (by one or multiple assessments with Szary
preparation/flow cytometry/Southern blot/poly-
merase chain reaction), and chest radiography.
Further imaging, including computed tomography,
was evaluated in the setting of lymphadenopathy or
clinically appreciable visceral disease. All patients
were evaluated by a dermatologist and radiation
oncologist. All patients were scored as having dif-
fuse erythroderma by 2 physicians and were staged
on the basis of the TNM classification.1 A total of 21
of the 44 patients received ECP in conjunction with
TSEB, which was then continued on a monthly basis
for a median of 6 months. The median age was 68
years (range, 29-82 years), and 66% were male.
At the time of initiation of TSEB, 57% were stage III,
59% had hematologic involvement (B1), 30% had
stage IVA (N3) disease, and 13% had stage IVB (M1)
disease. The median follow-up was 2.2 years (range,
0.3-13.9 years) subsequent to TSEB and 3.7 years
(range, 0.8-16.8 years) from diagnosis. A total of 27%
of the group was newly diagnosed and had not
received any previous therapy. For those who received
therapy for MF before treatment with TSEB, a total of
75 courses of therapy failed to control disease (15 sys-
temic therapy, 16 biologicals, and 44 topicals).
Pathology
Histologic material from biopsy specimens taken
before or at the time of consultation at Yale or
Hamilton were reviewed by dermatopathologists with
56 Wilson et al
expertise in cutaneous lymphomas. All cases were
confirmed as diagnostic for or consistent with MF in
conjunction with the clinical findings. Given the time
span over which patients were evaluated in this series,
blood was evaluated by Szary preparation or flow
cytometry, with confirmation via Southern blotting or
polymerase chain reaction if needed.
TSEB therapy
All patients provided consent before initiation of
TSEB, and treatment technique was similar at both
institutions. Patients were treated in a standing posi-
tion with a 6-treatment field arrangement as previ-
ously reported.3 A fixed horizontal beam was used
for all treatment at both centers until 1994, when a
dual-fixed angle beam arrangement was initiated at
Hamilton.
At Yale the surface dose ranged between 34 and 36
Gy, given over 9 weeks, 4 days per week, via 6 MeV.
The 6 fields were treated over a 2-day cycle, with the
skin receiving a mean dose of 1 Gy per day. Boost
fields included the scalp, perineum, and soles of feet,
which received 6 Gy, 20 Gy, and 20 Gy, respectively,
with 120 kilovolt (peak) (kV[p])(2mmAl) energy.
Internal eye shields were employed during the initial
18 Gy of TSEB, with subsequent external eye shield-
ing for the remainder of therapy. Hands and feet were
shielded on alternate days of treatment, with incor-
poration of nail shields for the hands when they were
exposed.
At Hamilton, patients received a total skin surface
dose of 32 to 40 Gy via 4 MeV. From 1980 to 1994,
this was administered to 11 patients in 12 fractions
over 3 weeks, using 3-day cycles (6 patient orienta-
tions). Subsequently, this was administered to 4
patients in 30 fractions over 6 weeks, using 3-day
cycles. The soles received a separate 4 MeV patch
field of 22.5 Gy/9 fractions/3 weeks before 1995, and
26 Gy/25 fractions/6 weeks subsequently. Shielding
of the eyes, hands, ankles, feet, groin, and lips was
applied for between 20% and 33% of the fractions, in
a routine manner. For example, eye protection was
used for 9 of 12 fractions between 1974 and 1994,
and for 21 of 30 fractions subsequently. Comparison
of results from the two centers demonstrate that
duration of therapy (as provided) does not influence
outcome.
ECP therapy
ECP was administered according to the protocol
elucidated by Edelson et al.4 Patients received treat-
ment on a monthly basis. Patients were given oral 8-
methoxypsoralen, typically 0.6 mg/kg, on 2 consecu-
tive days. Blood was then withdrawn 1 to 2 hours
after ingestion. Cells were centrifuged and leuko-
J AM ACAD DERMATOL
JULY 2000
cytes subsequently separated. Leukocytes were then
exposed to UVA light. A component bag including
240 mL of buffy coat, 300 mL of plasma, and 200 mL
of 0.9% normal saline, is exposed to UVA light. The
cells were then reinfused into the patient. This pro-
cedure was completed twice during the 2-day cycle.
All ECP treatment was given either neoadjuvantly,
concomitantly with TSEB, or initiated after comple-
tion of TSEB. If ECP was given before or during
TSEB, it was continued through the radiotherapy
course and continued afterward for a median of 6
monthly cycles. If given before TSEB, it was consid-
ered neoadjuvant because it was provided before
what was considered the primary therapy (TSEB) for
the purposes of this study.
Response
The response to treatment was assessed 1 to 2
months after completion of TSEB. Complete remis-
sion was defined as no visible erythematous cutaneous
lesions (no patches, plaques, or diffuse erythroder-
ma). A nonresponse means any detectable disease 2
months after completion of TSEB. Persistence or
recurrence of disease represents progression, and PFS
was evaluated from the initiation date of TSEB. For
those who were not in remission at the evaluation
point, the PFS was scored as a progression at time
zero. Those achieving remission had PFS measured
from initiation of TSEB until clinical results and biopsy
specimen examination confirmed recurrence. OS,
which relates to death from any cause, and cause-spe-
cific survival (CSS), which relates to death from MF,
were calculated from date of initiation of TSEB. Causes
of death either resulted from MF (sepsis, chemothera-
py related, visceral complication), other malignancy
(biopsy confirmed), cardiovascular (cerebrovascular
accident, myocardial infarction, embolism), or other
clearly determined etiology. Autopsy data were avail-
able in 8 cases.
Statistics
Univariate associations for binary categorical data
were evaluated for significance by means of the chi-
square method. Multivariate models included logistic
regression for response and Cox methods for event-
free survivals, with both backward and forward step-
ping methods. Potential factors in regressions were as
follows: age, gender, clinical history of failed previous
therapy, number of previous therapies, hematologic
involvement, nodal stage, stage IVA, stage IVB, surface
dose, and duration of TSEB. All P values are two-
sided, and statistical significance refers to P < .05.
Survival curves were generated through the method
of Kaplan-Meier, and two-way comparisons used
Mantel-Haenszel product moment methods.
J AM ACAD DERMATOL
VOLUME 43, NUMBER 1, PART 1
RESULTS
Prognostic factors
In addition to the administration of ECP, hemato-
logic involvement (B1) was significant with multi-
variate P values of .011, .017, .071, and .17 when
evaluated in relation to DFS, PFS, CSS, and OS,
respectively. Stage was also included as an adjusting
variable in multivariate regression analyses. Whereas
stage was not significant at a level of .05 in any
regression, it was the next strongest predictor of out-
comes, after hematologic involvement (B1), and as
compared with all other variables explored by uni-
variate and multivariate regression. P values for stage
were .182, .19, .08, and .17 for DFS, PFS, CSS, and
OS, respectively.
The median TSEB dose was 35.4 Gy (range, 32-40
Gy). The median total time for TSEB was 9 weeks.
Seven patients received 32 to 35 Gy, 11 received 35
Gy, 25 received 36 Gy, and 1 received 40 Gy. Twenty-
one of these patients also received ECP either initi-
ated before, during, or immediately after TSEB: 14
received ECP during the TSEB course and continued
after completion of TSEB; 4 received ECP after TSEB;
and 3 started ECP before TSEB and continued
through the TSEB course. The median follow-up was
2.2 years (range, 0.3-13.9 years) subsequent to TSEB
and 3.7 years from the time of diagnosis (range, 0.8-
16.8 years).
Characteristics of the TSEB and TSEB/ECP
groups
Variables, which included age, gender, number
and type of failed previous therapies, proportion of
B1 patients, stage III, stage IVA, stage IVB, dose, and
treatment time, were evaluated for the two groups of
patients. The only significant difference was noted in
the number of patients who had not responded to
previous therapy and the actual number of therapies
that failed. Those who received ECP had not
responded to previous treatment in 95% of cases,
compared with only 52% for the TSEB group (P =
.004). The actual number of failed therapies before
TSEB was 2.5 in the ECP group versus 1 for the TSEB
group (P = .004). No other differences were detect-
ed between the two groups.
Sequelae of ECP
ECP was well tolerated. Complications included
discomfort at the venipuncture site and mild tran-
sient hypotension. Infection related to the proce-
dure is rare.
Sequelae of TSEB
All patients experienced temporary alopecia, tran-
sient erythema and postinflammatory hyperpigmen-
Wilson et al 57
tation, and nail growth disturbance. Chronic seque-
lae included atrophy and mild xerosis. There was no
hematologic toxicity associated with TSEB.
Response
All patients responded to TSEB within 1 month of
completion. The CR rate was 73% for the entire
cohort and was 71% for those who received TSEB
alone versus 74% for those who received ECP as well.
This difference was not significant.
Subsequent therapies
A total of 49 subsequent courses of therapy were
given for progression. Patients were treated for pro-
gression if they failed to have a CR to TSEB or suf-
fered a clinical relapse after CR. A total of 8 patients
receiving TSEB/ECP, and 14 receiving TSEB did not
respond to therapy and required salvage therapy.
Twenty patients received systemic chemotherapy, 10
received biologic agents (including interferon in 6
and retinoids in 4), and 19 received topical therapies
(mechlorethamine = 9, PUVA = 2, steroids = 4,
topicals = 2, local radiotherapy = 1, and repeat
TSEB = 1).
PFS
The overall PFS for the entire patient population
was 51% and 47% at 2 and 3 years, respectively.
Those who received TSEB without ECP had 2- and 3-
year PFS of 36% for both time intervals. The 2- and 3-
year PFS for those who received TSEB and ECP were
66% and 58%, respectively. Multivariate Cox regres-
sion analysis revealed that after adjustment for blood
involvement and stage, the combination of TSEB and
ECP was superior to TSEB alone at a level of P =
.074, hence approaching significance.
DFS
A total of 32 patients had a CR to TSEB: 17
patients receiving TSEB without ECP, and 15 of
those receiving both modalities. Analysis of all indi-
viduals who achieved a CR to TSEB reveals a DFS of
68% at 2 years and 63% at 3 years for all patients.
When evaluated according to treatment method,
those who received TSEB had 2- and 3-year DFS of
49% at both time intervals, but those who were
treated with ECP in addition had improvement at
the 2- and 3-year intervals with figures of 93% and
83%, respectively. Multivariate Cox regression elu-
cidated that the addition of ECP was significantly
beneficial (P = .024) after adjustment for B1 and
stage. It is notable that for those patients who did
not have a CR to TSEB, the continuation or addi-
tion of ECP did not provide a CR in any of these 5
individuals.
58 Wilson et al
Fig 1. Cause-specific survival. Comparison of patients
who received extracorporeal photopheresis versus those
who did not. Multivariate regression demonstrated signif-
icant improvement in CSS with addition of ECP (P =
.048).
Mortality, CSS, and OS
A total of 19 patients from the cohort of 44 died.
Causes of death were MF related in 11 (58%).
Additional causes of death included second malig-
nancies in 4 patients, cardiovascular accident in 1,
well-defined other in 1, and unknown in 2. The 2-
and 3-year CSS for all patients was 82% and 63%,
respectively. Those who received TSEB without ECP
had 2- and 3-year CSS of 69% and 62%, respectively.
The addition of ECP offered improvement in 2- and
3-year CSS of 100% and 66%, respectively (Fig 1).
Multivariate Cox regression demonstrated a signifi-
cant improvement with the addition of ECP (P =
.048) after adjustment for B1 and stage.
OS for the entire group was 73% at 2 years and
57% at 3 years. When evaluated by treatment
method those who received TSEB without ECP had
2- and 3-year OS of 63% and 56%, respectively. Those
who received ECP in addition to TSEB had OS of 88%
and 58% at similar time intervals (Fig 2). These analy-
ses included all causes of death, and multivariate Cox
regression analysis failed to demonstrate a signifi-
cant improvement (P = .14) after adjustment for
stage and B1. However, hematologic involvement
and stage also were not found to be significant vari-
ables in multivariate analysis of OS. These results
may be explained by the 8 patients with causes of
death other than MF influencing the significance
level: 3 patients were in the TSEB/ECP group and 5
were in the TSEB group; 4 were B1 and 4 were B0; 2
were stage IVB and 6 were stage III. It is noted that
42% of the deaths were not attributable to MF, these
occurred in both groups of patients, and the effects
J AM ACAD DERMATOL
JULY 2000
Fig 2. Overall survival. Comparison of patients who
received extracorporeal photopheresis versus those who
did not. Multivariate regression demonstrated no signifi-
cant improvement in OS with addition of ECP (P = .14).
Hematologic involvement and stage were also not signifi-
cant factors in regression analysis for OS.
of therapy are expected to predict for only MF-relat-
ed events. This may explain why the P values associ-
ating OS and each of therapy (ECP), blood involve-
ment (B1), and stage are greater (meaning that they
are less, or are no longer, statistically significant)
than they are for CSS.
DISCUSSION
This series is retrospective and patients were
studied collectively from 2 centers. Given these limi-
tations, and recognizing potential bias, the data were
subjected to a multivariate analysis in an effort to
adjust for this. TSEB radiation has been effectively
used in the management of MF of all stages.5-13
Relatively few data are available regarding the effica-
cy of such treatment for patients with erythroderma
(T4).3 The therapeutic results and techniques have
been similar at Yale and Hamilton, and clinical evalu-
ation and outcome assessment are also consistent
among the two centers. Hence data have been
pooled and analyzed together in an effort to improve
the magnitude and quality of the analysis.
We recently published the largest modern experi-
ence with TSEB alone.3 When combined with a meta-
analysis of worldwide data published in 1995,5 this
establishes the basis for optimal dosing and results
relating to response rates, DFS, and OS for erythro-
dermic patients receiving TSEB alone without con-
comitant or adjuvant therapy.3 The rate of cutaneous
remission in that series was 60%, and 26% of the
cohort remained disease free at 5 years.3 Those
patients who received what we defined as more
intense (ie, optimum) TSEB (defined as doses of at
J AM ACAD DERMATOL
VOLUME 43, NUMBER 1, PART 1
least 32 Gy to the total skin with 4-6 MeV energy)
achieved a CR rate of 74%. Of this group, 36% was dis-
ease free at 5 years after TSEB alone. The median OS
for the group receiving 32 to 40 Gy TSEB was 3.7
years, with both a 5-year and 10-year OS figure of 36%.
The median CSS was 4.5 years, with 5- and 10-year fig-
ures of 45%. Both CSS and OS were associated with
hematologic involvement (P = .03), which has also
been demonstrated by the Stanford group.2
Therefore the rates of CR appear to be superior
with TSEB compared with other therapies for ery-
throdermic MF as demonstrated by the data report-
ed here, and from the recent series of newly diag-
nosed patients from Jones, Rosenthal, and Wilson.3
Despite an improvement in rates of remission with
TSEB as compared with other options, patients often
must travel long distances to receive TSEB because it
is not offered in all radiation therapy centers, and ther-
apy often lasts 6 to 10 weeks. The treatment is also
associated with sequelae such as exacerbation of ery-
thema during the course, alopecia, xerosis, and other
side effects previously reported. These treatment-
related effects are often used to justify patients receiv-
ing other modalities. However, TSEB on its own
appears to be an excellent palliative treatment for
patients with erythroderma and offers the opportuni-
ty for CR. Unfortunately, the results are often not sus-
tained at 3 years. The 3-year PFS is only 36%.3
Although a majority of these remissions are further
prolonged, the final 10-year PFS is just 26% after only
TSEB. Nevertheless, this finding justifies our strategy
of trying to combine TSEB with another active therapy.
The question then was which additional therapy has
sufficient activity to be combined with TSEB.
ECP is considered by many in the United States to
be the standard management choice for patients
with erythrodermic MF despite the lack of random-
ized data. Such therapy has not been performed on
a regular basis in Canada. The precise mechanism of
action through which ECP works is poorly under-
stood, but involves antineoplastic cell immunization,
which is mediated by CD8+ T cells. Many retrospec-
tive series have been noted with relatively small
numbers of patients, with various response rates,
and limited follow-up.4,14-20 Response rates have
ranged from 30% to 90%, and although CR has been
achieved through the use of ECP, long-term survival
data are lacking in the context of clinical trials or
from large retrospective databases. The first series to
demonstrate the use of ECP in the treatment of ery-
throdermic MF was that by Edelson et al4 in 1987. A
total of 29 erythrodermic patients were evaluated,
and 83% had a response to therapy. A follow-up
report of this series reported that the median sur-
vival of these patients was prolonged in comparison
Wilson et al 59
to a historic control group. Heald et al15 reported on
a group of erythrodermic patients in 1989. Nineteen
patients had erythroderma, and response rates were
similar to the series previously published. A variety
of other investigators have published reports of
small series with a range of response rates. More
recently, Zic et al19 published a series of 20 patients
with refractory disease. The CR rate with ECP was
25%, but 50% of those evaluated had no significant
response. Duvic, Hester, and Lemak20 reported a
50% response rate for 34 patients managed with ECP.
Fraser-Andrews et al21 reported the results of treat-
ment for 44 patients with erythrodermic MF. Those
who received ECP therapy had improvement in sur-
vival compared with those not treated with ECP, but
differences were not significant.
Given these results, we endeavored to evaluate
the effectiveness of combined modality therapy with
either the neoadjuvant, concomitant, or adjuvant
usage of ECP in combination with TSEB for patients
with erythroderma and MF. Wilson et al11 reported
that patients who had T3 or T4 MF and achieved a
CR after TSEB had a 5-year OS of 50% compared with
those who received adjuvant systemic chemothera-
py who had a 5-year survival of 75%. These differ-
ences were not significantly different (P < .34).
Seven patients who had a CR to TSEB also received
ECP and had an OS of 100% at 5 years, which did
approach significance (P < .06). Given the small
sample size, further study with additional patients
was obviously needed to clarify the usefulness of
either therapy or the combination.
The current series is the largest to date evaluating
TSEB in combination with ECP. The CR rates seen
after TSEB are not influenced by the neoadjuvant,
concomitant, or adjuvant usage of ECP. This is not
surprising because response rates with TSEB alone
have been relatively high (75%), and CR rates with
ECP have been low (25%). We suggest that PFS and
CSS were significantly influenced by the combined
modality approach with TSEB and ECP. The evalua-
tion is retrospective. Without randomization of treat-
ment assignment, selection bias may be a factor in
the results. Also, pooling data from two centers com-
plicates the interpretation even though methods of
TSEB were very similar. This series was subjected to
multivariate regression in an effort to address bias,
and a comprehensive evaluation of confounding
variables has been studied. Because blood status and
stage were previously identified as significant prog-
nostic features, we took these into account in the
multivariate analyses. The OS figures we report
appear to be favorable for the combination of ECP
and TSEB, but did not prove to be significant after
regression analysis. This may be explained in part, if
60 Wilson et al
not fully, by the fact that 8 patients died of causes not
related to MF, which influenced results.
This is the first study to suggest an improvement
in CSS and PFS for therapy in combination with
TSEB for patients with erythrodermic MF. Given the
low incidence of MF, and the rare erythrodermic
condition associated with it, it is unlikely that a ran-
domized phase III trial will be developed and that it
would attract significant numbers of patients for
study unless a coordinated effort is put forth on an
international level. Even if treatment is given with
palliative intent, TSEB offers an improved opportu-
nity for such a goal over other modalities, and the
addition of ECP further improves palliation. Other
questions remain: (1) What is the immunologic
mechanism through which ECP may be exhibiting its
effects? (2) What is the most appropriate sequencing
of TSEB and ECP? (3) What function do new thera-
pies and other biologic agents have in combined
modality regimens or as definitive treatment? The
present strategy offered at Yale is a concomitant
approach with initiation of ECP during the course of
TSEB. ECP has not been found to enhance adverse
reactions to electron beam, and patients are visiting
Yale 4 times per week for TSEB. This can be easily
coordinated with the ECP team so that patient travel
is minimized. When TSEB is completed, ECP usually
continues for 6 months on a monthly basis with
taper afterward as tolerated.
MF is a rare disease, and erythroderma is an
unusual manifestation of the disorder with signifi-
cant dermatologic sequelae that may cause severe
cutaneous discomfort, pruritus, exfoliation, infec-
tion, and cosmetic concerns. TSEB may offer the
greatest chance for CR for patients with erythroder-
mic (T4) disease, compared with other treatment
modalities. The addition of ECP appears to improve
both CSS and PFS. Future study needs to explore the
most appropriate sequencing of ECP in combination
with TSEB, in addition to elucidating the immuno-
logic mechanisms underlying the apparent success
of this combination.
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