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1292 Part VII Hematologic Malignancies

TABLE Treatment Strategies for Indolent Lymphomas TABLE Criteria for Delaying Treatment
80.6 80.7
Localized Disease GELF 26
Radiotherapy All of the following
“Watchful waiting” • Maximum diameter of disease <7 cm
Advanced Stage Disease • Fewer than 3 nodal sites
“Watchful waiting” • Absence of systemic symptoms
Chemotherapy • Spleen <16 cm on CT
Alkylating agents • No significant effusions
Bendamustine • No risk of local compressive symptoms
Purine analogs • No circulating lymphoma cells or marrow compromise
Combination chemotherapy (Hb ≤10 g/dL, WBC <1.5 or platelets <100,000/dL)
Monoclonal antibodies BNLI 27
Unconjugated Absence of all of the following
Conjugated—radioimmunoconjugates and immunotoxins
Chemotherapy + monoclonal antibodies (chemoimmunotherapy) • B symptoms or pruritus
High-dose chemotherapy plus autologous/allogeneic stem cell • Rapid generalized disease progression
transplantation • Marrow compromise (Hb ≤10 g/dL, WBC <3.0 or platelets
Reduced intensity conditioning allogeneic transplantation. <100,000/dL)
Palliative radiotherapy • Life-threatening organ involvement
• Renal infiltration
• Bone lesions
BNLI, British National Lymphoma Investigation; CT, Computed tomography;
GELF, Groupe pour l’Etude de Lymphome Folliculaire; Hb, hemoglobin; WBC,
Management of Follicular Lymphoma white blood cells.
Patients most often present with asymptomatic lymphadenopathy.
The diagnosis should be made by excisional biopsy and reviewed by
an expert hematopathologist. In the absence of symptoms requiring
treatment, an expectant “watch and wait” approach is the treatment all be appropriate depending on clinical circumstances. This treat-
of choice. While in this phase of treatment patients should be followed ment option is offered with curative potential but has to be weighed
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every 3–6 months for history, physical, and laboratory examination against the potential toxicity in terms of the radiation therapy to
with radiologic restaging as clinically indicated. Once a decision to other tissues. In patients with large tumor burden or with other
treat has been made, there is no clear treatment algorithm and a adverse risk factors, systemic therapy is indicated. There is no proven
number of treatment options are available. The treatment goal, whether
palliative or potentially with curative intent, is dependent upon the role of radiation consolidation therapy.
age and performance status of patients. Enrollment in a clinical trial
should be the treatment of choice. For younger patients in whom
high-dose therapy may be indicated later in their disease course, it is Bulky Stage II and Stage II/IV Disease
best to avoid profoundly myelotoxic regimens. Rituximab maintenance
therapy in first remission given 2-monthly for two years has been Expectant management is the treatment of choice for asymptomatic
demonstrated to improve progression-free, but not overall survival. patients with low-bulk disease until clear indications for initiation of
The role of maintenance therapy in first remission using interferon-α treatment are seen, except for those patients enrolled in a clinical trial
remains controversial. The choice of therapy after first relapse is also assessing the impact of early therapy. This approach is based upon the
dependent upon the goal of therapy, but is also dependent upon the
previous therapy given, response, and duration of response. Autologous demonstration of no survival advantage for institution of immediate
or allogeneic stem cell transplantation has a role to play in selected treatment compared with deferred treatment until time of progres-
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younger patients with this disease. sion. Three randomized trials, performed in the pre–rituximab era,
confirmed no survival benefit for early therapy. 25–27 In the National
Cancer Institute study in 104 newly diagnosed patients with FL,
deferred treatment was compared with immediate treatment with
with history, physical exam, and blood counts including LDH. ProMACE-MOPP followed by total nodal irradiation. An updated
Special attention should be paid to any change in symptoms that analysis of this data is long overdue, but there was no difference
might be suggestive of transformation as these are an indication for in overall survival (OS) between the two arms at the time of the
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a repeat biopsy to examine for histologic evidence to confirm trans- last analysis. The Groupe pour l’Etude de Lymphome Folliculaire
formation. Repeat scanning is not routinely performed unless this is (GELF) used defined criteria for patients for whom immediate
indicated by symptoms or signs. therapy was not felt to be indicated (Table 80.7) and randomized
Since there is no clearly defined treatment algorithm for most 193 patients to deferred treatment or to receive prednimustine
2
patients with FL, eligible patients should be included whenever pos- 200 mg/m per day for 5 days per month for 18 months or IFN-α
sible in clinical trials. This ensures delivery of optimal care and helps 5 million units (MU)/day for 3 months followed by 5 MU three
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inform design of subsequent trials, hopefully leading to cure. Infor- times per week for 15 months. The median OS time was not
mation on available clinical trials can be found at http:// reached and was the same in all three arms of the study. The British
27
www.clinicaltrials.gov. National Lymphoma Investigation (BNLI) compared treatment
in 309 patients with asymptomatic advanced-stage, indolent lym-
phoma in whom 158 patients were randomized to receive immediate
WHEN TO INSTITUTE THERAPY therapy with oral chlorambucil 10 mg per day continuously and
151 patients were randomized to deferred treatment until disease
Stage I–II Disease progression (see Table 80.7). In both arms, local radiotherapy to
symptomatic nodes was allowed. There was no difference in OS or
Involved site radiation therapy is the preferred treatment for the cause-specific survival between the two groups with median follow
approximately 10% of patients who present with limited stage, up of 16 years. A subsequent multicenter study examined whether
nonbulky disease. Treatment with photons, electrons, or protons may rituximab could delay the need for chemotherapy or radiotherapy