UPLC-Tandem Mass Spectrometry for Quantification of Busulfan in Human Plasma: Application to Therapeutic Drug Monitoring.

Busulfan (Bu) is an alkylating agent commonly used in preparative regimens for hematologic malignant and non-malignant patients undergoing hematopoietic stem cell transplantation (HSCT). The objective of the present study was to develop an UPLC-MS/MS method for quantification of Bu in human plasma. A total of 55 patients with hematologic malignancies (n = 34) and non- malignancies (n = 21) received myeloablative Bu therapy prior to HSCT. A tandem mass spectrometric method was developed and validated to quantify Bu levels in these patients. The method was fully validated over the concentration range of 25-2000 ng/mL (r > 0.99). The assay method demonstrated good precision and accuracy. Stability studies indicated that the drug was stable in various conditions. Incurred sample reanalysis findings were within acceptable ranges (<15% of the nominal concentration). Based on the 1st dose AUC results, one third of hematologic malignant patients and half of non-malignant patients needed dose adjustment. However, in subsequent doses (5th, 9th, and 13th), 77%, 82% and 82%, respectively, of hematologic malignant patients and 71%, 67% and 86%, respectively, of non-malignant patients achieved the target range of Bu AUC. The suitability of the developed method for routine TDM of Bu in HSCT patients was demonstrated. The study suggests that the pharmacokinetic profile of Bu varies in both groups.

Representation of expatriates among cancer patients in Kuwait and the need for culturally-competent care.

From 2000 to 2007, 11,793 cancer patients received treatment in Kuwait. Non-Kuwaitis accounted for 6,016 (51%) patients. They came from 68 countries, mainly from the World Health Organization Eastern Mediterranean (59%) and South-East Asian (20%) regions. The majority (69%) was from low- and low-middle income countries. Thirty-seven percent were from non-Arabic speaking countries. To provide culturally-competent care for expatriate patients, there is a need to explore the impact of their ethnic, sociocultural, economic, language diversity, and expatriation-related stressors on different aspects of cancer care.

The palliative prognostic index for the prediction of survival and in-hospital mortality of patients with advanced cancer in Kuwait.

INTRODUCTION: Prognostic scoring systems are increasingly used in cancer care. One of these systems is the Palliative Prognostic Index (PPI) which is based on clinical findings. Few studies validated the PPI in different settings. Our aim was to test the predictive value of the PPI in an acute cancer care setting. METHODS: Prospective study that included patients with advanced cancer admitted to a tertiary cancer center in Kuwait. Patients were divided according to the PPI score into three groups: A (PPI≤3), B (PPI>3- ≤6), and C (>6). RESULTS: The study included 91 hospitalized patients. At the time of PPI assessment, the plan of treatment was best supportive care only in 70 (77%) patients. The majority (80%) of included patients died in-hospital. The in-hospital mortality rate for patients with a PPI>6 was significantly higher than those with ≤6 (93% versus 56%, p<0.001). Using a cutoff point of PPI>6, in-hospital mortality was predicted with a 73% sensitivity, 78% specificity, 93% positive predictive value, and 41% negative predictive value. The median survival was 61 days (95% confidence interval [CI]: 25.8-96.2) for group A, 20 days (95% CI: 4.5-35.5) for group B, and 6 days (95% CI: 4-8) for group C. The difference in survival was highly significant (p<0.001). CONCLUSION: The results suggest that the PPI may be helpful for oncologists in predicting survival and in-hospital mortality of patients with advanced cancer in the acute care setting.

Frequencies of non-Hodgkin's lymphoma subtypes in Kuwait: comparisons between different ethnic groups.

There is a wide variation in the prevalence of various subtypes of non-Hodgkin's lymphoma worldwide. The aim of this study was to determine the relative frequency of different subtypes of non-Hodgkin's lymphoma in Kuwait based on the Revised European-American Lymphoma (REAL) classification. From 1998 to 2006, 738 subjects were included that were registered with non-Hodgkin's lymphoma in the population-based cancer registry at the Kuwait Cancer Control Center. Expert pathologists reviewed histological slides from all subjects. We performed detailed immunohistochemical studies and classified subjects based on the REAL classification. The prevalence of different types of non-Hodgkin's lymphoma was determined based on age, sex, site of disease, and ethnicity. Ethnicity groups comprised Kuwaiti Arabs, non Kuwaiti Arabs, Asians, and others. The prevalence of B- and T-cell lymphomas was 81.8% and 14.2%, respectively. The most common age group was 41-60 years old. The three most common subtypes in Kuwaiti Arabs were diffuse large B-cell lymphoma (46.5%), follicular lymphoma (15.5%), and mycosis fungoides (9.3%). In non-Kuwaiti Arabs, the most common subtypes were diffuse large B-cell lymphoma (48%), B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (15.8%), and follicular lymphoma (12.7%). Overall, non-Kuwaiti Arabs exhibited the highest prevalence (59%), and 54% of all cases had extranodal presentation. Compared to the Western world, Kuwait had a lower prevalence of follicular lymphoma, a higher prevalence of diffuse large B-cell lymphoma and extranodal presentation, and a high frequency of mycosis fungoides. Compared to other parts of Asia, Kuwait had a lower frequency of peripheral T-cell lymphomas.