Risk Factors

A number of prognostic factors have been analyzed for their association with transformation. In a series examining histologic progression of follicular lymphomas, it was noted that patients who transformed were more likely to have had early stage disease at initial diagnosis and were more likely to have received local radiation as primary treatment when these patients were compared to others with unchanged histology.5 In another series, histologic transformation was found to be associated with involvement of extranodal sites of disease, stage IV disease, presence of systemic symptoms, and bulky abdominal disease at diagnosis, as well as failure to achieve a complete remission with initial therapy.6 Lack of response to initial therapy has been associated with a higher risk of transformation in other series,21 and it has been suggested that eradication of primary disease with initial therapy may reduce the incidence of transformation. Elevated serum ^-microglobulin level was associated with a higher risk of transformation in one series.21

Other series have failed to identify risk factors associated with transformation.716 It does not appear that an initial "watch-and-wait" strategy alters the risk of transformation.17 Similarly, the risk of transformation appears to be similar when patients with follicular large-cell lymphoma are compared to patients with follicular small cleaved-cell and follicular mixed-cell lymphomas.21 Treatment with fludarabine or other nucleoside analogs was not shown to influence the progression of CLL to large-cell lymphoma in one series,3 although other groups have shown unexpectedly high rates of histologic transformation in patients with CLL and follicular lymphoma who were treated with fludarabine.23 The Stanford group found that the risk of histologic conversion was not influenced whether patients were initially treated with involved-field radiation, total lymphoid or whole body irradiation, single-agent chemotherapy, or combination chemotherapy.16

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