Busulfan (Bu)-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2mg/kg/day (FBD) given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring (TDM) of Bu. We compared the Bu dose given using TDM with the FBD of 3.2mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15years (range 2-55years) with 57% adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients, while the remaining 54% were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39mg/day with a statistically significant difference (p<0.001) even after adjusting for the weight (median total FBD of 349mg, median TDM dose of 494mg, p<0.0001). Age and underlying condition (malignant vs. nonmalignant) were the main factors affecting Bu clearance (p<0.001 and p<0.07, respectively). TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture.
Most anticancer agents show wide variability in pharmacokinetics (PK) and have a narrow therapeutic index which makes fixed dosing suboptimal. To achieve the best therapeutic outcomes with these agents, many studies have postulated using PK or therapeutic drug monitoring (TDM)-guided dosing. However, multiple factors contribute to the variability in PKs making the application of TDM in practice challenging. Also, despite the known association with clinical outcomes, standard guidelines on PK-guided dosing are lacking for most agents. Understanding the factors that contribute to PK variability and their impact is essential for dose individualization. The purpose of this review is to discuss the factors that contribute to the PK variability of anticancer agents and the challenges faced in practice when individualizing doses for certain widely used agents. Searching the literature has identified several gaps and efforts are needed to ensure better targeting of cancer therapeutics.
Objectives We sought to assess the prevalence of gestational trophoblastic diseases (GTD) among pregnant women at Sultan Qaboos University Hospital (SQUH) and compare our results with the international studies. We also sought to determine the risk factors, histological features, sonographic findings, and outcomes in women with GTD. Methods We conducted a retrospective cohort study of all women diagnosed with GTD and followed at SQUH between November 2007 and October 2015. We collected data on maternal demographics, risk factors, sonographic features, histological diagnosis, follow-up period, and chemotherapy treatment from the hospital information system. Results Sixty-four women with GTD were included in the study with a mean age of 31.0±7.5 years, mean gravidity 4.0, and parity 2.0. The prevalence of GTD was 0.3% (one in 386 births), and the most common risk factors were increased maternal age and multiparity. A partial hydatidiform mole was diagnosed in 54.7%, complete hydatidiform mole in 43.8%, and invasive mole in 1.6% of women. Eleven percent of women required chemotherapy. Typical ultrasound features for partial molar pregnancy were present in 54.7% of our sample, while snowstorm appearance was seen in 89.3% of those with complete mole. Negative beta-human chorionic gonadotropin was achieved 70 days after diagnosis in 41 women. Conclusions The awareness of the risks and complications of GTD among physicians with close follow-up is paramount. There is a need to establish a national registry of GTD cases in Oman.
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Objectives: This study was conducted to assess pregnancy outcomes in women with systemic lupus erythematosus (SLE) in Oman. Methods: A retrospective cohort study of 149 pregnancies in 98 women with SLE was conducted over 10 years to evaluate the impact of clinical and laboratory parameters in predicting adverse pregnancy outcomes. Results: Mean maternal age was 30.6 ± 5 years ranging from 20–44 years, and the mean disease duration was 10 ± 5 years, ranging from 2–27 years. The most common maternal manifestations were joint pain in 36 (24.2%), lupus nephritis (LN) in 18 (12.08%), preeclampsia in 11 (7.4%), eclampsia in three (2%) and lupus flare in one pregnancy. The live birth rate was 139 (93.3%) with a mean gestational age of 36 ± 2 weeks ranging from 26–40 weeks. In total, 55 (39.6%) were preterm deliveries, six (4%) pregnancies ended in miscarriage, and four (2.7%) resulted in intrauterine fetal death. Intrauterine growth restriction was observed in 49 babies (35%). A significant association was found between hypertension (HTN) and miscarriage (P = 0.024) and preterm birth (P = 0.019). In addition, HTN was positively associated with preeclampsia (P = 0.004) and LN (P = 0.048). Antiphospholipid syndrome impacted preterm birth (P = 0.013) and postpartem haemorrhage (PPH) (P = 0.027) and was found to be a significant predictor for women developing deep vein thrombosis and pulmonary embolism (P <0.001 for both). Conclusion: Despite potential complications, most pregnancies complicated by SLE in Oman result in good outcomes. Adverse pregnancy outcomes, however, may still occur in women with SLE. In women with SLE, pregnancy planning, careful antenatal monitoring and efficient SLE treatment need to be undertaken for successful pregnancy outcomes. Keywords: Systemic Lupus Erythematosus; Pregnancy Outcomes; Lupus Nephritis; Antiphospholipid Antibodies; Neonatal Lupus.
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