Long-term efficacy of imatinib in a practical setting is correlated with imatinib trough concentration that is influenced by body size: a report by the Nagasaki CML Study Group.

Imatinib has dramatically improved long-term survival of chronic myelogenous leukemia (CML) patients. To analyze its efficacy in a practical setting, we registered most of CML patients in Nagasaki Prefecture of Japan. Of these, 73 patients received imatinib as an initial therapy. The overall survival rate of these patients was 88.7% at 6 years, and the cumulative complete cytogenetic response rate was 82.5% at 18 months. These results are comparable with the data of other reports including the IRIS study; however, the administered imatinib dose was smaller in our study than that in other reports. To address these discrepancies, we measured the trough concentration of imatinib among 35 patients. Although 39% of the patients were administered less than 400 mg/day, the trough level was comparable to those of previous reports. The trough level of imatinib showed a significant relationship with its efficacy, and was clearly related to dose of imatinib administrated and dose of imatinib divided by body surface area (BSA). Considering the smaller BSA of Japanese patients as compared to those of foreign origin, the results suggest that a lower dose of imatinib could maintain enough trough level and provided excellent results for the treatment of CML in our registry.

Primary T-cell lymphoma of the thyroid gland with chemokine receptors of Th1 phenotype complicating autoimmune thyroiditis.

Lymphoma of the thyroid is almost exclusively derived from B cells of mucosa-associated lymphoid tissue (MALT), and frequently co-exist with autoimmune thyroiditis in which most infiltrating cells are of Th1 cell origin. We present here two rare cases of peripheral T-cell lymphoma (PTCL) based on chronic thyroiditis with the phenotype CD3+, CD4+, CD8-, TCR+. Furthermore, lymphoma cells in both cases were CXCR3+, CCR5+ and ST2(L)-, suggesting a Th1 cell origin. Eight of 11 cases of PTCL of the thyroid in the literature, including our cases, were associated with thyroiditis. Except for one tumor of T-cell type, all of the five lymphomas analyzed for CD4 expression were positive for the antigen. Among them, both those examined for chemokine receptors were phenotypically of Th1-cell origin with a background of thyroiditis, suggesting that Th1 activation induced by chronic inflammation could lead to PTCL of themselves as well as MALT-lymphoma of B cells.