Pharmacogenetics and the treatment of chronic myeloid leukemia: how relevant clinically? An update.

Despite the excellent efficacy and improved clinical responses obtained with imatinib mesylate (IM), development of resistance in a significant proportion of chronic myeloid leukemia (CML) patients on IM therapy have emerged as a challenging problem in clinical practice. Resistance to imatinib can be due to heterogeneous array of factors involving BCR/ABL-dependent and BCR/ABL-independent pathways. Although BCR/ABL mutation is the major contributory factor for IM resistance, reduced bio-availability of IM in leukemic cells is also an important pharmacokinetic factor that contributes to development of resistance to IM in CML patients. The contribution of polymorphisms of the pharmacogenes in relation to IM disposition and treatment outcomes have been studied by various research groups in numerous population cohorts. However, the conclusions arising from these studies have been highly inconsistent. This review encompasses an updated insight into the impact of pharmacogenetic variability on treatment response of IM in CML patients.

A comparison between infrared tympanic thermometry, oral and axilla with rectal thermometry in neutropenic adults.

BACKGROUND: This study assessed the agreement between infrared tympanic membrane (TM), axillary, corrected axillary (+0.5 degrees C), oral, and corrected oral (+0.3 degrees C) to rectal thermometry as reference standard in neutropenic adults. The sensitivity and specificity of the mentioned thermometries in detecting rectal fever (> or =38 degrees C) were also analysed. METHOD: This is a comparative diagnostic test study. A total of 400 sets of blinded simultaneous temperature readings were measured from 21 haemato-oncology in-patients with neutropenia following chemotherapy. Three-hundred sets were then randomly sampled. Agreements were analysed using random two-way intraclass correlation (ICC). Sensitivity and specificity were analysed using contingency 2x2 table. FINDINGS: Both right and left TM thermometry have good correlation with rectal thermometry; 0.810 (95% CI, 0.748-0.855) and 0.770 (95% CI, 0.713-0.815) respectively. Axilla thermometry has weak agreement (ICC 0.486 (95% CI, 0.118-0.689)) with rectal thermometry. The sensitivity (sn) and specificity (sp) in detecting rectal fever (> or =38 degrees C) were: right TM (sn) 0.712 (95% CI, 0.586-0.814), (sp) 0.957 (95% CI, 0.920-0.978); oral (sn) 0.561 (95% CI, 0.433-0.681), (sp) 0.983 (95% CI, 0.954-0.995); and axilla (sn) 0.348 (95% CI, 0.238-0.477), (sp) 0.996 (95% CI, 0.973-0.999). INTERPRETATION: Single tympanic membrane thermometry is in good agreement with rectal thermometry. It is more sensitive than oral or axillary thermometry in detecting rectal fever.