A 6 8 10 12 14 16

time (years)

Figure 67.1 Overall survival of 74 patients with follicular low-grade NHL following histologic transformation. (Reprinted from Ref. 22)

months for patients who relapsed with a nodular pattern, as compared with 17 months for those who relapsed with a diffuse pattern (P = 0.068).15 The median survival among patients from Vanderbilt University with indolent lymphoma was 2.5 months for those who exhibited histologic transformation, as compared with 37.5 months for those who retained their initial histologic pattern (P < 0.001).7 Median survival following histologic progression was 4 months in a series of follicular low-grade lymphomas from Denmark,6 and 12 months in a series from Iowa.26 The median survival following histologic transformation was approximately 1 year in a series from London.20 In another series of 74 patients from Stanford, the median survival was 22 months following transformation (Figure 67.1).22 Limited stage at the time of transformation (P = 0.01), absence of prior therapy (P = 0.01), and response to therapy (P = 0.005) were associated with longer survival after transformation. These results have been used to support the use of a "watch-and-wait" approach for the initial management of patients with low-grade follicular lymphomas. Finally, a French series examined outcomes of patients with follicular lymphomas who were treated on phase III trials.27 The 5-year survival was estimated to be 15% for patients with subsequent transformation, as compared to 45% for those who retained follicular architecture (P = .00001).

These results demonstrate that histologic transformation is frequently associated with aggressive clinical behavior and poor survival. In some series, overall survival from the time of diagnosis was shorter in patients who subsequently demonstrated histologic progres-sion.5 7 Nevertheless, transformation may be a late event in the course of disease, and survival from the time of diagnosis may not be different when patients with unchanged histology are compared to patients who have undergone transformation.1516

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