Follicular Lymphoma

Clinical Features

§        Widespread disease at diagnosis

§        LNs, spleen, bone marrow (90%), Waldeyers ring

§        10% have localised disease at diagnosis

§        Modification of the IPI score used to stage – FIPI

Morphology

§        Lymph nodes

§        Neoplastic follicles poorly defined

§        Closely packed follicles

§        Graded (I-III) by the proportion of centroblasts (Grade III = >15 per high power field)

§        IIIb classified as aggressive lymphoma – better response to anthracycline-based chemotherapy

§        Histological grade correlates with prognosis

§        Blood

§        Small circulating lymphocytes with cleaved nuclei

Immuno

§   Positive : SIg, Bcl2, Bcl6, CD10, B-cell markers

§   Neagtive : CD5, CD43

Genetics

§   T(14;18) = BCL2 with Ig heavy chain

Treatment

Stage I/II disease

§        Radiotherapy alone standard treatment for stage I and II indolent lymphoma

§        40% disease free at 10 years (MacManus and Hope)

§        Concerns about secondary malignancies in the radiation field

§        Combined chemotherapy and radiotherapy aimed at cure – no RCTs to support this

Stage III/IV

§        Standard approach in elderly patients is to ‘watch and wait’

§        Early treatment of asymptomatic lymphoma has not been shown to improve survival in studies from the 80s and 90s ie the pre rituximab era

§        Over half of patients with early stage disease may not need any therapy after 6 years

§        Single agent chlorambucil for elderly patients

§        Combination chemotherapy

§        CVP v CHOP

§        Addition of anthracyclines improves outcome

§        Fludaribine with cyclophosphamide, mitoxantrone

§        Monoclonal antibodies often added (rituximab)

§        Rituximab also used for maintenance

§        High dose therapy

§        Currently under investigation

§        Auto and Allografting seem to have similar 5 year survival (50-60%) with the reduced remission rates being offset by the higher TRM of allografting

§        Good GVL effect possibly due to epitopes generated by BCL2 rearrangement

Novel approaches

§        Radiolabelled antibodies (eg Y90)

§        Most active single agents in relapsed disease

§        Remissions lasting several years have been seen in some patients

§        Need <25% bone marrow involvement and adequate leukocyte and platelet counts

§        Tumour vaccine

§        Anti-idiotype proteins for the tumour specific immunoglobulin expressed on individual B-cell lymphomas