Guidelines on Diagnosis and Treatment of Malignant Lymphomas

Potential Pitfalls
a. Failure to differentiate from reactive disease
b. Failure to differentiate from mantle cell lymphoma
c. Failure to grade and especially to distinguish grade 3b
d. Failure to recognise as a component of DLBCL
(diffuse large B-cell lymphoma) when FL has
undergone high- grade transformation
Treatment
Stage I /II
Radiation therapy with curative intent is the treatment of
choice. Involved field radiotherapy using doses of 24-40Gy
with potential dose adaption according to disease response
should be used.
Stage III/IV
Conventional treatment is not curative and there is no evidence
that early treatment of asymptomatic patients improves overall
survival. Treatment should be delayed until disease becomes
symptomatic, leads to critical organ impairment or undergoes
high- grade transformation. Spontaneous regression may occur
in 10- 20% of patients being observed.
The least toxic, effective treatment should be used to avoid long
term effects in patients who may have a prolonged survival.
Patients should be treated to a stable or asymptomatic disease
status and then observed until disease progression. At this stage
re-evaluation is undertaken (tissue sampling and re-staging) and
further treatment planned. Disease which has not progressed for
>2 years may be managed without escalated therapy. This
approach results in a median survival of 8-13 years with patients
receiving an average of 3 courses of treatment. Younger patients
with good performance status at first or second progression
should be considered for potentially “curative approaches” using
stem-cell transplantation.
Single agent chemotherapy
Chlorambucil: can be used as pulse therapy (10mg/m2) for
5 days every 28 days or continuous low dose therapy, usually
for 6 months resulting in an ORR of about 80%. Chlorambucil is
stem cell toxic and should be avoided if a stem cell harvest is
being considered.
Fludarabine: Results in an ORR rate of 30-60% in relapsed
disease and should be avoided if a stem cell harvest is
being envisaged
Rituximab: Active in >80% as a single agent in de novo patients
and 65% of previously treated/refractory patients. No data
supports its use as a first line single agent, but it may be useful in
patients with compromised marrow or poor performance status.
Combination chemotherapy
R-CVP has an ORR of 81% and EFS of 32 months after 8 cycles.
R-CVP is not stem cell toxic and is useful first line therapy in
patients 65 years.
R-combination (anthracycline-containing): R-CHOP is indicated
for rapid disease control, in disease refractory to non-anthracycline
containing therapy, in patients with grade 3 disease or as second
line therapy. The use of RCHOP as primary chemotherapy is
associated with a lower rate of high grade transformation.
Rituximab maintenance (RM) can be given in various schedules
of which the commonest is Rituximab 375mg/m2 every 3 months
for 2 years. A meta-analysis confirms the survival advantage of
RM as part of the primary therapy and at relapse.
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