Mohammed Al-Huneini

Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

OBJECTIVES Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX) side effects in patients with thalassemia major or intermedia. METHODS A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female) with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period. RESULTS Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s) in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline), feeling unwell (2), severe diarrhea (1), pregnancy (1), death unrelated to chelator (2) and rise in serum transaminases (2). Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013). CONCLUSION Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.

Safety of stem cell mobilization in donors with sickle cell trait

High WBC plays a major role in the pathogenesis of many of the complications seen in patients with sickle cell disease (SCD).1 Individuals with Sickle cell trait may develop SCD-related complications in conditions of severe stress.2 G-CSF increases the WBC and may contribute to some of the complications in individuals with sickle cell trait when used in stem cell mobilization. To the best of our knowledge, only one small study3 assessed the safety of the mobilization of stem cells in individuals with sickle cell trait. Herein, we aimed to compare mobilization adverse events between donors with and without sickle cell trait.

Rituximab leads to long remissions in patients with chronic immune thrombocytopenia

OBJECTIVES To assess the response rate and duration of response in patients with chronic immune thrombocytopenia (ITP) receiving rituximab. METHODS We retrospectively analyzed 32 consecutive patients with chronic ITP who were treated in two tertiary centers in Oman. Response assessment was based on the American Society of Hematology criteria. RESULTS Nineteen patients (59%) had an initial response. However, six of the 19 patients lost their response leaving 13 patients with long-lasting remissions. The median age at diagnosis was 25 years (range 14-58). The median time from diagnosis to rituximab therapy was 21 months. The median follow-up after starting rituximab was 26 months. The overall cumulative response rate was 59% (complete response 44%, partial response 15%) and the median time to respond was 30 days with a response rate of 44% at four weeks. In all responders, the cumulative rate of loss of response was 32% with a median time to lose response of 54 months. CONCLUSIONS The use of rituximab in ITP achieves high response rate and long remission duration. Our study was limited by the small sample size and further larger prospective studies are recommended.

Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients

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.

First Implementation of Transfusion Consent Policy in Oman : Audit of compliance from a tertiary care university hospital

OBJECTIVES Transfusions are a common medical intervention. Discussion of the benefits, risks and alternatives with the patient is mandated by many legislations prior to planned transfusions. At the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, a written transfusion consent policy was introduced in March 2014. This was the first time such a policy was implemented in Oman. This study therefore aimed to assess adherence to this policy among different specialties within SQUH. METHODS The medical records of patients who underwent elective transfusions between June and August 2014 were reviewed to assess the presence of transfusion consent forms. If present, the consent forms were examined for completeness of patient, physician and witness information. RESULTS In total, the records of 446 transfused patients (299 adult and 147 paediatric patients) were assessed. Haematology patients accounted for 50% of adult patients and 71% of paediatric patients. Consent was obtained for 75% of adult and 91% of paediatric patients. The highest adherence rate was observed among adult and paediatric haematology specialists (95% and 97%, respectively). Consent forms were correctly filled out with all details provided for 51% and 52% of adult and paediatric patients, respectively. Among inadequately completed forms, the most common error was a lack of witness details (20-25%). CONCLUSION In most cases, the pre-transfusion consent policy was successfully adhered to at SQUH. However, further work is required to ensure full compliance with the consent procedure within different specialties. Implementation of transfusion consent in other hospitals in the country is recommended.

Acute massive splenic infarction with complete liquefaction of the spleen in sickle cell disease

To the Editor: The link between splenic sequestration and massive infarction has been noted by several authors.1,2 Large splenic infarcts have been reported in sickle cell trait patients with normal sized spleens, an event precipitated by hypoxia during high altitude flights in an unpressurised aircraft or during mountain climbing. Massive splenic infarction has also been reported in patients with other sickle cell variants, where splenomegaly is common mainly in Hb sickle cell disease (SCD), in Sβ+ thalassaemia and Hb SE disease.3 Many of these patients start with splenic sequestration syndrome, followed by clinical deterioration leading to splenic infarction. In SCD, infarction is reportedly induced by stressful conditions including severe generalized painful crisis, septicemia, the postoperative period, strenuous exercise and in the postpartum state. It has also been reported following high altitude travel, including flying in modern pressurized aircraft. Hence SCD patients with splenomegaly are advised against air travel when possible, and if deemed unavoidable, they are advised to have a pre-travel simple or exchange transfusion in addition to adequate hydration. In a study of 134 SCD patients who underwent splenectomy in Saudi Arabia, only two patients (1.49%) had massive splenic infarction.3 Repeated attacks of vaso-occlusion, which are usually small and often asymptomatic leading to splenic infarction, often occur in children and result in autosplenectomy. However a significant number of SCD patients in Oman (60%) have preserved splenic function with some splenomegaly, well into adulthood, making them liable for splenic complications including sequestration and infarction.4,5 The preserved spleen is due in part at least to the high prevalence of both alpha-thalassaemia (48%), and betathalassaemia (2.6%) in the country.5 Similar results in the temporal sequence of splenic dysfunction in SCD have been reported by others in the region.6 While splenic infarction is a well recognized complication of SCD, massive splenic infarction with complete liquefaction of the spleen is rarely reported.7 We report our experience with three patients with SCD who had massive splenic infarction among a large number of patients with SCD who had splenectomy (Table 1, 2). All our patients with splenic sequestration had elevated HbF at a mean of 7.1% in general and 22% among the three patients with massive infarction. Noticeably, patients with massive splenic infarction had a significantly elevated HbF (P=.0001, unpaired t test). Although elevated HbF is usually compatible with a milder course for SCD, and in association with thalassaemia, helps to preserve the spleen into adulthood, high Hb F in these patients did not seem to protect them from getting splenic infarction or sequestration.8 On the contrary, this study suggest that a significantly elevated HbF may indeed be a predictor of high risk for massive splenic infarction when the spleen is preserved into adulthood, and under conditions that may lead to tissue hypoxia like stress, infections, hypoxia, strenuous exercise and high altitude. Sickling of erythrocytes occurs in efferent channels of the spleen, which sets a chain of reactions that progressively involves more efferent channels culminating in a large splenic infarction. Studies of blood flow through the spleen done during periods of acute splenic sequestration, verify that blood flow is greatly retarded and sluggish.7 Therefore, in the presence of the above precipitating factors, patients with SCD who develop acute splenic sequestration are at risk of Table 1. laboratory test results in sickle cell disease patients, including three patients with massive splenic infarction.

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.

Hematopoietic stem cell transplantation in the Sultanate of Oman

The Sultanate of Oman is one of the Arabian Gulf countries with a total population of 4,414,051 as of mid 2016, of which 2,427,825 are Omanis. The gross national income per capita was 7327.7 RO (Omani rial; equivalent to US

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

19,033) in 2014. There are two hematopoietic stem cell transplantation (HSCT) centers in Oman: the Sultan Qaboos University Hospital (SQUH; allogeneic and autologous) and the Royal Hospital (RH; autologous). HSCT activity in Oman started in 1995 at the SQUH center, which had only one bed, and four cases were performed in that year. The number of allogeneic HSCTs at the SQUH ranged between four and 29 cases per year, of which malignancy was the main indication for transplantation (47%). Most of the transplants were performed from identical sibling donor. T-deplete haploidentical and recently T-replete haploidentical HSCT were also performed at the SQUH center. In the allogeneic HSCT cohort transplanted at the SQUH, the risk of acute graft-versus-host disease (Grades II-IV) was 18%, whereas the risk of extensive chronic graft-versus-host disease was 8%. The HSCT unit at the RH, which started in 2014, performs autologous HSCT procedures only. The number of autologous HSCT cases at the RH ranged between three and 16 cases per year. Limited bed availability is a frequent obstacle to HSCT in Oman. Construction of a much larger national HSCT center is about to be completed, which will likely improve access to transplant services in Oman.

Stem Cell Transplantation in Patients with Sickle Cell Disease

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.