Stem Cell Transplantation in Patients with Sickle Cell Disease

Hematopoietic stem cell transplantation (HSCT) is currently the only established cure for sickle cell disease (SCD). Replacement of the stem cell that has the defective beta globin allele with the normal gene decreases hemoglobin S and the risk of complications of SCD. The first case reported was a girl with acute myeloid leukemia and SCD who received HSCT and achieved long-term SCD and leukemia-free survival. Given the favorable outcomes of HSCT with thalassemia major using myeloablative preparative regimens, this approach became widely used in the initial studies of HSCT in SCD. The current standard of care is to use a myeloablative stem cell transplantation in patients with severe disease who have human leukocyte antigen–identical sibling. HSCT improves organ function, quality of life, and overall and disease-free survival. However, this is associated with high risk of gonadal dysfunction and graft versus host disease in addition to the mortality associated with the myeloablative HSCT. Reduced-intensity HSCT has also been reported with high rates of engraftment and favorable outcomes. This has been introduced to lower the gonadal dysfunction, mortality, and graft versus host disease associated with myeloablative approaches. Other approaches include HSCT using matched unrelated donors, cord blood units, and human leukocyte antigen haploidentical donors. Unfortunately, graft rejection is a common complication with these approaches. In this chapter, we review the indications of HSCT for SCD and outcomes of different transplant strategies including alternative donor transplant, graft rejection, and infertility after transplantation

Impact of Home-to-Centre Distance on Bone Marrow Transplantation Outcomes

Objectives: Haematopoietic stem cell transplantation (HSCT) in Oman started in 1994 at Sultan Qaboos University Hospital (SQUH), Muscat, Oman. Previous studies have suggested that longer driving time to the transplant centre (DTC) independently correlates with worse overall survival (OS). Therefore, this study aimed to examine the impact of DTC on OS and acute graft-versus-host disease (aGvHD). Methods: This retrospective study included all patients who underwent HSCT between February 2006 and December 2016 at SQUH. The DTC was determined using Google Maps (Google LLC., Mountain View, California, USA). The probability of OS was estimated using a Kaplan-Meier estimator and the impact of DTC on OS was compared using a Cox model. Results: A total of 170 patients were included in this study of which 52% were male and 28% were from the Al Batinah region. The mean age was 14.2 ± 12.2 years. The mean haemoglobin, platelet and white blood cell counts before the HSCT were 10.3 ± 1.7 g/dL, 207 ± 131 × 109/L and 5.1 ± 5.9 × 109/L, respectively. The median DTC for those with aGvHD was 84 minutes, which is similar to patients without aGvHD (P = 0.918). The hazard ratio for DTC as a predictor of OS was 1.0 (P = 0.901). Conclusion: In this single centre study, DTC did not impact aGvHD or OS in patients post-HSCT. The study was limited by its retrospective design and the small sample size. It is recommended that these results be confirmed in a prospective study. Keywords: Hematopoietic Stem Cell Transplantation; Graft Versus Host Disease; Survival Analysis; Travel; Oman

Perinatal Outcome in Pregnancies with Extreme Preterm Premature Rupture of Membranes (Mid-Trimester PROM)

Preterm premature rupture of membranes (PPROM) is defined as the rupture of fetal membranes before 37 weeks. Extreme PPROM occurs before 26 weeks’ gestation and can result in perinatal morbidity and mortality. The aim of this study was to study the perinatal outcomes of mothers with extreme PPROM. Methods: A retrospective cohort study of 44 consecutive pregnant women, presenting with PPROM before 26 weeks’ gestation, was conducted from January 2006 to December 2011 at Sultan Qaboos University Hospital, Oman. Maternal and neonatal information was collected from medical records, and delivery and neonatal unit registries. Women with PPROM presenting after 26 weeks’ gestation, those with multiple gestations, or other types of preterm deliveries were excluded from the study. Results: Of the 44 preterm infants admitted to the Neonatal Intensive Care Unit, 24 (55%) survived, 7 (16%) died within 24 hours of birth, 9 (20%) were miscarried, and 4 (9%) were stillbirths. Neonatal sepsis and pulmonary hypoplasia were the major causes of death. Neonatal complications among the surviving infants included prematurity in 11 (46%), respiratory distress syndrome in 19 (79%), sepsis in 12 (50%), and low birth weight in 11 (46%). The neonatal survival rate was significantly associated with the gestational age at delivery but not with the gestational age upon rupture of membranes. Conclusion: Extreme PPROM was associated with adverse perinatal outcomes. The results of this study will help obstetricians and neonatologists in counselling couples experiencing PPROM. Future studies of long-term neonatal morbidityshould have larger sample sizes and include more hospitals

Echocardiographic Evidence of Early Diastolic Dysfunction in Asymptomatic Children with Osteogenesis Imperfecta

Objectives: Structural and functional cardiovascular abnormalities have been reported in adults with osteogenesis imperfecta (OI); however, there is a lack of paediatric literature on this topic. This study aimed to investigate cardiovascular abnormalities in children with OI in comparison to a control group. Methods: This case-control study was conducted at the Sultan Qaboos University Hospital in Muscat, Oman, between May 2013 and August 2014. Data from eight patients with OI and 24 healthy controls were compared using conventional and tissue Doppler echocardiography (TDE). Results:The OI group had significantly lower peak early mitral valve flow velocity (P = 0.027), peak a-wave reversal in the pulmonary vein (P = 0.030) and peak early diastolic velocity of the mitral valve and upper septum (P = 0.001 each). The peak late diastolic velocities of the mitral valve (P = 0.002) and the upper septum (P = 0.037) were significantly higher in the OI group; however, the peak early/late diastolic velocity ratios of the mitral valve (P = 0.002) and upper septum (P = 0.001) were significantly lower. Left ventricular dimensions and aortic and pulmonary artery diameters were larger in the OI group when indexed for body surface area. Both groups had normal systolic cardiac function. Conclusion: Children with OI had normal systolic cardiac function. However, changes in myocardial tissue Doppler velocities were suggestive of early diastolic cardiac dysfunction. They also had increased left ventricular dimensions and greater vessel diameters. These findings indicate the need for early and detailed structural and functional echocardiographic assessment and follow-up of young patients with OI

Unusual Indolent Course of a Chronic Active Epstein-Barr Virus-Associated Natural Killer Cell Lymphoproliferative Disorder

Natural killer (NK) cell lymphoproliferative disorders are uncommon and the Epstein-Barr virus (EBV) plays an important aetiological role in their pathogenesis. We report a 20-year-old male with a chronic active EBV infection associated with a NK cell lymphoproliferative disorder which had an unusual indolent course. He presented to the Sultan Qaboos University Hospital in Muscat, Oman, in December 2011 with a history of intermittent fever and coughing. Examinations revealed generalised lymphadenopathy, hepatosplenomegaly, leukocytosis, transaminitis, diffuse bilateral lung infiltrates and bone marrow lymphocyte involvement. A polymerase chain reaction (PCR) test revealed a high EBV viral load in the peripheral blood cells. The patient received a course of piperacillin-tazobactam for Klebsiella pneumoniae, but no active treatment for the lymphoproliferative disorder. However, his lymphocyte count, serum lactate dehydrogenase and liver enzymes dropped spontaneously. In addition, EBV PCR copies fluctuated and then decreased significantly. He remained clinically asymptomatic over the following four years.

Knowledge and Attitudes Towards Clinical Trial Participation in Oman: A cross-sectional study

Objectives: Clinical trials are prospective studies on human subjects designed to answer various clinical questions. However, only a limited number of clinical trials have been conducted in Oman. This study aimed to assess the knowledge and attitudes of Omani patients and their relatives towards participating in clinical trials. Methods: This cross-sectional study was conducted between October 2015 and March 2016 among 174 patients and relatives attending the Haematology and Oncology Outpatient Clinics and Day Care Unit of the Sultan Qaboos University Hospital, Muscat, Oman. A self-administered questionnaire was designed to elicit participants’ knowledge of and attitudes towards participation in clinical trials. Results: A total of 100 patients and relatives agreed to take part in the study (response rate: 57.5%). The male-to-female ratio was 1:1.2. Only 31.3% of the studied population knew what clinical trials were and only 6.5% had themselves previously participated in a clinical trial. The majority agreed or strongly agreed that they would participate in clinical trials related to their own condition (59.2%). Overall, 89.7% expected to be informed about potential clinical trials by their treating physicians. Conclusion: Omanis had a low level of knowledge of clinical trials and a very low rate of previous participation in such trials, despite a moderate level of interest. Patients should therefore be educated and informed of ongoing clinical trials in order to improve participation rates for clinical trials conducted in Oman

Impact of Blood Transfusion on Troponin I Levels and Outcomes after Cardiac Surgery: A Cohort Study

Objectives: Increased cardiac troponin I (TI) has been suggested to be a sensitive indicator of intraoperative myocardial injury. We investigated the association of transfusion on TI levels post-surgery and outcomes in patients undergoing elective cardiac surgeries. Methods: We conducted a retrospective review of 542 patients. Patients were divided into two groups based on TI levels at 24 hours (TI24) (> 6.5 µg/L vs. ≤ 6.5 µg/L). The impact of transfusion on TI levels was estimated using logistic regression and adjusted for using a multivariable model that included aortic cross-clamp time and preoperative ejection fraction. The effect of TI on the clinical outcomes was examined. Results: Red blood cell (RBC) transfusion was found to be associated with high TI levels (odds ratio (OR) = 2.33, p = 0.007, 95% confidence interval (CI): 1.30–4.30). A trend was observed when aortic cross-clamp time and preoperative ejection fraction were adjusted for (OR = 2.06, p = 0.080, 95% CI: 0.90–4.70). An association was found between aortic cross-clamp time and high TI levels in the multivariable model (OR = 1.01, p = 0.028, 95% CI: 1.00–1.02). Elevated TI levels was associated with higher mortality (OR = 4.15, p = 0.017, 95% CI: 1.29–13.08), renal failure (OR = 2.99, p = 0.004, 95% CI: 1.41–6.32), and increased length of stay in-hospital (OR = 4.50, p = 0.020, 95% CI: 0.69–8.30). Conclusions: RBC transfusion is associated with increased TI24 post-cardiac surgery and worse outcomes, albeit a confounding effect cannot be excluded. Larger studies are required to confirm these findings

Non-Invasive Haemoglobin Estimation in Patients with Thalassaemia Major

Objectives: This study aimed to validate pulse CO-oximetry-based haemoglobin (Hb) estimation in children and adults with thalassaemia major (TM) and to determine the impact of different baseline variables on the accuracy of the estimation. Methods: This observational study was conducted over a five-week period from March to April 2012. A total of 108 patients with TM attending the daycare thalassaemia centre of a tertiary care hospital in Muscat, Oman, were enrolled. Spot (Sp) Hb measurements were estimated using a Pronto-7® pulse CO-oximetry device (Masimo Corp., Irvine, California, USA). These were compared to venous samples of Hb using the CELL-DYN Sapphire Hematology Analyzer (Abbott Diagnostics, Abbott Park, Illinois, USA) to determine the reference (Ref) Hb levels. A multivariable linear regression model was used to assess the impact of baseline variables such as age, gender, weight, height, Ref Hb and blood pressure on the Hb estimations. Results: Of the 108 enrolled patients, there were 54 males and 54 females with a mean age of 21.6 years (standard deviation [SD] = 7.3 years; range: 2.5–38 years). The mean Ref Hb and Sp Hb were 9.4 g/dL (SD = 0.9 g/dL; range: 7.5–12.3 g/dL) and 11.1 g/dL (SD = 1.2 g/dL; range: 7.5–14.7 g/dL), respectively. The coefficient of determination (R2) was 21% with a mean difference of 1.7 g/dL (SD = 1.1 g/dL; range: −0.9–4.3 g/dL). In the multivariable model, the Ref Hb level (P = 0.001) was the only statistically significant predictor. Conclusion: The Pronto-7® pulse CO-oximetry device was found to overestimate Hb levels in patients with TM and therefore cannot be recommended. Further larger studies are needed to confirm these results

Impact of Aberrant Myeloid Antigen Expression on Outcomes of Patients with T-cell Acute Lymphoblastic Leukemia

Objectives: To evaluate the impact of myeloid antigen expression on complete remission (CR), event-free survival (EFS), and overall survival (OS) in patients with T-cell acute lymphoblastic leukemia (T-ALL) treated with intensive chemotherapy. Methods: We retrospectively reviewed consecutive patients diagnosed with T-ALL and treated in Sultan Qaboos University Hospital and Royal Hospital in Oman between 2004 and 2010. The diagnosis of T-ALL was established using French-American-British classification or World Health Organization criteria. Patients were considered having myeloid antigen expression if they expressed CD13, CD33, or both (My+ and My–). Results: Of the 39 patients, 38 were included in the study (25 patients with My– and median age of 18.4 years, 13 patients with My+ and median age of 22.0 years). Median follow-up was 12 months. Thirty-two out of the total cohort were eligible for response-rate assessment. Twenty-nine patients (90.6%) achieved CR with one or two courses of chemotherapy with similar CR rates between the two groups (p = 0.880). Twenty-five percent (5/20) of the patients with My– required two courses of induction, whereas 58.3% (7/12) of My+ required two courses of induction and the difference was statistically significant (p = 0.040). In the multivariable analysis; age, gender, initial white blood cell count, central nervous system disease, and myeloid antigen expression were not statistically significant predictors of CR. The EFS and OS were similar between the My+ and My– groups p = 0.180 and p = 0.440, respectively. Conclusions: Patients with T-ALL with myeloid antigen expression need more courses of induction; however, rates of CR, EFS, and OS are not different from those without myeloid antigen expression. Larger prospective studies are required to confirm these findings