Results are expressed as nmol of 6-MMP produced per mL of packed erythrocytes per hour of incubation at 37°C. If the samples were not assayed immediately, they were stored at -70°C. However, all samples were assayed within four days of collection. Repeat analysis of one sample showed an interassay precision of 100% over the course of the study.
Of the 29 patients enrolled in the study, 15 were randomized to group 1 and, thus, did not have their TPMT activity determined. The remaining 14 were randomized to group 2, and their TPMT activity tested as normal. The demographics of the groups were similar except for the difference in sex between the two groups.
Eight patients from group 1 and eight patients from group 2 (53% and 57%, respectively) withdrew from the study (Table 3). Five patients in each group withdrew due to intractable clinical symptoms of nausea, vomiting, myalgia, fatigue, leg cramps or headaches. One patient in group 1 developed leukopenia (2.2×109/L) seven months after starting AZA and was withdrawn. Two patients in group 1 developed elevated liver enzymes (ALT 82 U/L, AST 52 U/L and GGT 165 U/L and ALT 329 U/L, AST 302 U/L and GGT 503 U/L, respectively) at two weeks and two months after drug initiation, respectively, and were withdrawn.
TABLE 3 Reasons for withdrawal from the study
|Reasons for withdrawal||Group 1 (n=8)||Group 2 (n=8)|
|Nausea, vomiting, myalgia,||5||5|
|fatigue, leg cramps or headaches, n|
|Elevated liver enzymes, n||2||0|
|No therapeutic effect, n||0||2|
Group 1: No thiopurine methyltransferase assay before initiation of azathioprine; Group 2: thiopurine methyltransferase assay performed before initiation of azathioprine