Initial treatment of advanced FL and SLL

Three options are available: (1) watch and wait; (2) conventional chemotherapy and/or radiotherapy; (3) intensive chemotherapy and/or radiotherapy.

Watch-and-wait: therapy may be deferred for many months/years after diagnosis until clinical symptoms develop. Patients may have better quality of life and avoid exposure to cytotoxic agents but must be monitored closely to prevent or identify insidious complications promptly. Overall survival >80% at 5 years.

Conventional therapy: generally involves one of the following approaches:

• Chlorambucil (0.1-0.2mg/kg/d x 7-14 days, q28 or 0.4-0.6mg/kg every 2 weeks) or cyclophosphamide (50-150mg/d PO) as single agents or with prednisolone; response rates of 50-80% after 12-18 months' treatment; most relapse within 5 years; convenient oral regimen; well tolerated.

• 'Simple' combination chemotherapy e.g. CVP: more rapid response than chlorambucil (useful with bulky disease or symptomatic patients) but otherwise similar: response rates 80-90%; median response 1.5-3 years; few durable remissions; IV and oral regimen; causes alopecia.

• 'High grade' regimens: high 'CR' rates (~60%) with CHOP-type regimens but continuous pattern of relapse and overall survival not convincingly improved in indolent FL (histological grades I and II). In histological 'grade III' FL CHOP produces results equivalent to those in DLBCL (see below).

• Radiotherapy for treatment of local problems e.g. cord compression.

Intensive therapy: patients with high tumour burden and high LDH who achieve CR have significantly longer survival (63% at 10 years). To improve the CR rate high dose chemotherapy ± TBI followed by autologous SCT (with monoclonal antibody purging of the 'graft' in some centres) has been utilised in younger patients with advanced FL and/or poor prognostic features after initial response to chlorambucil or CHOP. ~80% CR rate; 66% overall survival and up to 40% DFS at 8 years. Still largely investigational; continuing risk of relapse; too early to assess effect on long term survival. Myelodysplasia develops in up to 15% of heavily pre-treated long-term survivors.

Relatively few allografts have been undertaken. Most use TBI-containing conditioning. CR rate >80% and relapse rates are clearly lower than after autograft (12% vs. 55% at 5 years) and very few after 2 years. Curative potential requires longer follow-up. The benefit of better disease control is offset by a higher treatment-related mortality (15-30%). Non-myeloab-lative regimens may reduce toxicity, preserve the GvL effect and widen the availability of this treatment. AlloSCT should be considered in appropriate patients with poor prognosis disease. Total lymphoid (or nodal) irradiation may achieve very high CR rates with 5-year DFS rates >60% 202 but is rarely utilised due to toxicity.

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