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"—," Absent; "+," present; "+/—," may be present; OS4y, 4 year overall survival; ULN, upper limit of normal. a Patients with ATL who do not fit criteria for smouldering, chronic, or lymphoma subtypes. b With T lymphocytes >3.5 X 109/L (including abnormal T lymphocytes).

c If abnormal T lymphocytes in PB <5%, patients should have biopsy-proven malignant lesion(s). d Biopsy-proven; +/— no specific qualification.

"—," Absent; "+," present; "+/—," may be present; OS4y, 4 year overall survival; ULN, upper limit of normal. a Patients with ATL who do not fit criteria for smouldering, chronic, or lymphoma subtypes. b With T lymphocytes >3.5 X 109/L (including abnormal T lymphocytes).

c If abnormal T lymphocytes in PB <5%, patients should have biopsy-proven malignant lesion(s). d Biopsy-proven; +/— no specific qualification.

Modified from Shimoyama et al. 1991.

and median survivals of 4.7-10 months.1635-37 Attempts to improve the response rates and OS led to the incorporation of multiple non-cross-resistant agents, extended duration of therapy, and incorporation of intrathecal chemotherapy (in an attempt to prevent meningeal recurrence), yielding CR rates of 17-44% (Table 63.2).1'24'31-33'38-44 Responses were not durable and significantly lower for patients with ATL compared with B-cell non-Hodgkin's lymphoma or peripheral T-cell lymphoma.383942 Reported response durations were less than 8 months,3244 and median OS was only 5.5-13 months.

These studies32,38,39,42,44 demonstrate the limitations of treating patients with ATL with conventional agents. The lack of good-quality responses (i.e., CRs) achieved with chemotherapy is a consequence of several factors: intrinsic resistance of ATL cells secondary to P-glycopro-tein overexpression, mutations of the tumor suppressor gene p53, expression of the free-radical scavenger, ATL-derived factor, and abnormalities of topoisomerase II activities.45-50

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