Page 1543 - Hematology_ Basic Principles and Practice ( PDFDrive )

1370 Part VII Hematologic Malignancies

PUVA therapy to patients with stage IA–IIA disease (see Table 85.5),
How We Manage Mycosis Fungoides/Sézary Syndrome
monitoring patients with tumor disease closely for progression.
There is no current accepted standard first-line approach or sub- Side effects associated with PUVA are quite tolerable. Nausea or
sequent lines of therapy for patients with mycosis fungoides and vomiting due to psoralen ingestion is observed occasionally, and
Sézary syndrome. Published guidelines include active drugs/treatment erythema, pruritus, and chronic dry skin are effects of the UVA
approaches, but unfortunately few randomized trials have been com- damage. Long-term PUVA exposure has been associated with a
pleted to allow for comparative effectiveness. Our philosophy regarding number of delayed effects. These include dry skin, lichenification,
management is to try to avoid the side effects of therapy being worse keratosis, and rarely amyloid deposition in the skin. Most important
than the symptoms from the disease. Thus for patients with limited is the late development of iatrogenic (basal and squamous) carcino-
cutaneous only disease (stage I–IIa) we favor topical therapy alone with mas, secondary malignant melanomas of the skin, and rarely cataract
either limited topical steroid/drug applications for T1 stage disease (and formation. Because the cumulative dose of PUVA is correlated with
for more extensive T2 stage disease our preference is ultraviolet light-
based approaches, but other centers utilize topical chemotherapy or the risk for developing a second skin cancer, routine use of mainte-
total skin electron beam radiation therapy). For patients with T2 thicker nance therapy may be less desirable, especially for patients with an
plaque disease we would consider a topical plus systemic therapy such excellent prognosis (stage IA). Despite these problems, the long
as interferon (IFN) or targretin depending upon ages and comorbidities remissions induced, the ease of administration, and the lack of
of patients. For patients with tumor stage or generalized erythroderma/ interactions with other therapeutic modalities make PUVA an attrac-
Sézary syndrome, and visceral involvement (stages IIb–IVb) we would tive early intervention.
favor initially a systemic agent such as IFN or targretin with some Narrow-band UVB (wavelength of 311 nm) is emerging as a valid
topical agents, and total body ultraviolet light or extracorporeal photo- alternative to PUVA for patients with limited patch or plaque disease.
pheresis (Sézary), and limited radiation to tumors (stage IIb). If these Although probably not as effective as PUVA, initial studies reported
approaches do not control disease we favor attempting any of the
systemic chemotherapy drugs or ideally an appropriate clinical trial. For RRs near 70%. The advantages of narrow-band UVB are that oral
younger/healthier patients with heavily pretreated refractory disease we psoralen is not required and there may be less of a photocarcinogenic
consider earlier use of allogeneic stem cell therapy. effect. The role for maintenance therapy has not been established.
UVA-1 is a modality of phototherapy that uses high-energy
UVA1 (340–400 nm) output, which penetrates deep into the
dermis. Resolution of tumor lesions has even been reported using this
+
therapeutic approach. However, the reduction in circulating CD4
exposed in vitro to PUVA undergo apoptosis. Unfortunately, normal cells raises the possibility that chronic use of this modality could be
and neoplastic lymphocytes were equally sensitive to the apoptosis immunosuppressive.
induced by PUVA (as opposed to with psoralen alone). However,
macrophages appeared to be resistant to apoptosis induction and
phagocytized apoptotic lymphocytes (but not nonapoptotic lympho- Radiation Therapy
cytes). Apoptosis induction may be the ultimate end point yielding
benefit, but an immunologic effect due to monocyte phagocytosis The CTCLs have been shown to be radiosensitive. External-beam
and antigen presentation resulting from effector cells may also be radiation adequately controls local areas of otherwise resistant MF or
present. provides palliation in cases of bulky tumor lesions. Unfortunately, the
Photochemotherapy units with UVA lamps emit a continuous cumulative dosage that can be given to patients over time is limited
spectrum of long UVA in the range of 320–400 nm with peak due to organ toxicity. Side effects consisting of leukopenia, thrombo-
emission between 350 and 380 nm. Initial exposure times of patients cytopenia, and radiation-induced dermatitis may prevent long-term
to high-output UVA are based on the degree of pigmentation before therapy with other agents. Newer techniques involving total nodal
therapy, history of ability to tan, and the output of the photochemo- irradiation, fractionated total-body irradiation, and limited fraction
therapy units. Exposure times are increased with each treatment lesional irradiation all may have a role to play in the development of
depending on the patient’s response and evidence of erythema. The multimodality approaches to this disease. There has been little
2
initial UVA dose is between 0.5 and 2.0 J/cm and can be increased comparative research into methodology for external beam radiation
2
by approximately 0.5 J/cm per treatment as tolerated. The psoralen that provides guidance to clinicians.
compound is ingested 2 hours before the UVA exposure. Topical We recently reviewed our outcomes with a single fraction of
psoralen protocols are also available. UV-blocking glasses should be external beam radiation, which was hypothesized to optimize conve-
worn for 24 hours after administration of 8-MOP. Therapy is typi- nience and minimize expense to patients. Two hundred and seventy
cally given three-times weekly until complete clearing occurs. The individual lesions in 58 patients were primarily treated with more
frequency of treatments can then be reduced, but some maintenance than 700 cGy (97%). With a mean follow-up of 41 months, 94.4%
therapy (once every 2–4 weeks) may prolong the duration of remis- of lesions completely responded, and 3.7% partially responded.
sion. As data have emerged regarding the long-term risks of secondary Predictors of poor response included lower extremity lesion, tumors,
skin malignancies after PUVA, the advisability of this maintenance and lesions exhibiting large-cell transformation. Lesions treated with
therapy has been questioned. electron beams had a higher CR rate than those treated with photon
Initial trials using PUVA benefited psoriasis patients. Clinical beams. Cost estimates have suggested multifractionated radiation was
trials with PUVA for patients with MF soon followed. These studies 200% more expensive than the single fraction.
all demonstrated high rates of remission in the early stage (patch or The limitations of external beam radiation led to increasing use
plaque stage of disease). The Scandinavian study group reported a of electron beam radiotherapy for cases of MF confined to the skin.
58% CR rate for these patients within 4–12 months of initiation of Linear accelerator-generated electron beams are scattered by a pene-
therapy. Maintenance therapy was associated with a remission dura- trable plate placed at the collimator site. The energy of the electrons
tion of up to 53 months. In these early studies, the same group also is reduced to 4–7 MeV and allows adequate field distribution.
reported a surprisingly high rate of objective remissions in tumor- Because of this low energy level, the beam only penetrates the surface
stage patients of 83%. In a large series, 82 patients were followed for several millimeters to 1 cm into the dermis. Patients may be treated
a median of 43 months. An ORR was observed in 95% of patients, using six-field or rotational treatments. The total skin surface can be
with a 65% complete clearance rate. Ninety percent of these patients treated without significant internal organ toxicity. Most patients are
had early-stage disease (stage IA–IIA). A single patient with tumor- able to tolerate total doses of approximately 3000–3600 cGy over an
stage disease attained a short remission with PUVA alone. Two of six 8–10-week period.
patients with generalized erythroderma cleared completely (no evi- An excellent review compared results of external beam therapy at
dence of circulating neoplastic lymphocytes). Given the difficulty in Stanford University with those achieved in Hamilton, Ontario
treating advanced-stage patients with PUVA alone, we usually restrict (Canada). The results cited in this paper reflect the extensive expertise