Clinicopathological Profile of Paroxysmal Nocturnal Hemoglobinuria among Omani Patients: A Case Series.

We aimed to estimate the nature and prevalence of paroxysmal nocturnal hemoglobinuria (PNH) among Omani patients. We performed a retrospective review of all patients who were tested for PNH by flow cytometry at the Sultan Qaboos University Hospital, Muscat, between 2012 and 2019. Manifestations, treatment modalities, and outcomes were assessed. A total of 10 patients were diagnosed or were on follow-up for PNH (median age 22.5 years). Clinical manifestations included fatigue (80%) and anemia (70%). Six patients had classical PNH with hemolysis, three had PNH in the context of aplastic anemia, and one patient had subclinical PNH. The median total clone size (type II + III) for neutrophils was 95.5 (range: 1.5-97) (FLAER/CD24) and for monocytes was 91.6 (range = 0.04-99) (FLAER/CD14). Four patients had clone sizes > 50% at the time of diagnosis. The median follow-up period of the patients was 62 months (range = 8-204 months). One patient suffered thrombosis. Three patients were on immunosuppressant agents, five were initiated on eculizumab, and four had a bone marrow transplant. No deaths were reported in the cohort. The estimated average incidence of PNH among Omani patients was 1.5 per 5 000 000. PNH is rare in the Omani population. The predominant presentation is hemolytic anemia.

Busulfan clearance does not predict the development of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a life-threatening complication following hematopoietic stem cell transplant (HSCT). Busulfan has a narrow therapeutic index and its concentration was found to correlate with VOD. Our primary objective was to assess the association between busulfan clearance and VOD in HSCT patients. In this retrospective analysis, we included patients who received their HSCT between 2003 and 2014 and followed at Sultan Qaboos University Hospital. All patients who received dose-targeted busulfan-containing conditioning were included. Target steady-state concentration (Css) was 800-900 ng/ml. VOD was assessed using modified Seattle criteria. The impact of busulfan clearance on VOD was analyzed using univariable logistic regression model. Seventy-three patients were included with a mean age of 15 years. Of those, 47% were transplanted for hematological malignancies and 53% for inherited hemoglobinopathies. Target Css was achieved in 85% of patients. The rate of VOD was 17%. There was no significant impact of busulfan clearance (p = 0.919) or area-under-the-concentration-time-curve (p = 0.275) on VOD. Targeting busulfan Css into narrow therapeutic range may have accounted for the findings. The risk of VOD might be related to other factors such as the genetic background, and more studies are required to investigate these factors.

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.

First Cytogenetic Profile of Omani Patients with de novo Myelodysplastic Syndromes: Comparison with data from Asia, Africa, Europe and North and South America.

Clonal cytogenetic abnormalities have been reported among 30-80% of patients with myelodysplastic syndromes (MDS); however, 20-70% of patients with MDS show a normal karyotype that may nevertheless harbour a cryptic genetic alteration. Earlier reports have suggested that the distribution of specific chromosomal aberrations varies among Western and Asian countries, with geographical and ethnic differences in the frequency of specific chromosomal aberrations. This article compared the cytogenetic data of 36 adult Omani patients with MDS to previously reported data from other populations. Differences were noted between the percentages of clonal aberrations and the median age of Omani subjects at presentation in comparison to individuals of different ethnicities and from various geographical locations. To the best of the authors' knowledge, this is the first report to describe the cytogenetic data of patients with MDS from Oman.

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$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.

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.

Transfusion Consent in Oman: Physicians' Perception at a Tertiary Care University Hospital.

OBJECTIVES: Transfusion is a common intervention that mandates the discussion of benefits, risks, and alternatives to planned transfusions. In Oman, transfusion consent was first introduced at the Sultan Qaboos University Hospital in March 2014. We sought to evaluate our physicians' opinions, attitudes, and perception of the transfusion consent process. METHODS: Attending physicians of different specialties were invited to complete an anonymous survey on transfusion consent. RESULTS: A total of 114 physicians responded to the survey. Transfusion benefits and risks were explained regularly by 91% and 87% of the surveyed physicians, respectively. On the other hand, alternatives were declared by only 38%. Discomfort with the consent process was admitted by 10% of the physicians. There was no statistically significant association between discomfort in obtaining the consent and the physician seniority (p = 0.801), nor their specialties (p = 0.623). The importance of the consent process was acknowledged by 80% of surveyed physicians, who supported its implementation in other hospitals. CONCLUSION: This survey reflects positive attitudes of the surveyed physicians on the importance of transfusion consent. However, actions are required to achieve physicians' full ease with the process and to ensure that transfusion alternatives are discussed. We advocate implementation of transfusion consent in other hospitals in Oman.

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.

Biclonal Gammopathy in Chronic Lymphocytic Leukemia: Case Report and Review of the Literature.

Monoclonal gammopathies are frequently seen in B-cell malignancies. Monoclonal proteins are seen in a significant proportion of patients with chronic lymphocytic leukemia (CLL), which is a clonal disorder of mature B cells. The use of more sensitive laboratory methods has enabled the detection of monoclonal proteins or light chains in the serum and/or urine in the majority of these patients. The presence of some of these monoclonal proteins may explain the different autoimmune phenomena that are associated with this disease. Some reports indicate that the finding of monoclonal proteins has a negative impact on patients' survival. The presence of two different monoclonal proteins (i.e. biclonal gammopathy) is on the other hand rare. Most of the reported cases in the literature are of patients with plasma cell disorders. In this report, we describe a rare occurrence of biclonal gammopathy in a patient with CLL. Serum protein electrophoresis and immunofixation, which were negative at the time of initial diagnosis, showed biclonal immunoglobin A (IgA) kappa and IgA lambda during the course of the disease. The patient's disease showed steady progression, despite multiple treatments. Although this could just be the result of using more sensitive laboratory techniques, biclonal gammopathy in this patient likely reflects the evolution of another clone, which would explain the encountered resistance to therapy. Because of paucity of reports, the impact of biclonal gammopathies in such patients is not known and an effort to collectively report the presentation and outcome of these patients is needed to further understand the pathophysiology and clinical significance of such a finding.

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.

Lymphoproliferative Disorders in Patients with Chronic Myeloid Leukemia: A Single-Center Case Series.

Lymphoproliferative disorders presenting simultaneously with or subsequent to the occurrence of chronic myeloid leukemia (CML) have rarely been reported. Herein, we report 8 cases of a variety of lymphoproliferative conditions associated with CML at different times during the course of the disease. All 8 patients were treated with tyrosine kinase inhibitors at some point during the course of their illness. The literature regarding the uncommon association of these apparently unrelated disorders is reviewed as well as the possible underlying mechanisms that could be associated with this phenomenon.

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 (R(2)) 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.

Acute Allograft Renal Vein Thrombosis: A Case Report.

Renal graft thrombosis is a serious and devastating complication of renal transplant that ultimately results in graft loss. It is associated with acute and hyper-acute rejections; however, the underlying cause in large proportion of patients remains unknown. We report a case of a young male who underwent live related kidney transplant but lost the graft on the operating table due to renal vein thrombosis (RVT).

Successful management of severe hemolytic disease of the fetus due to anti-Jsb using intrauterine transfusions with serial maternal blood donations: a case report and a review of the literature.

BACKGROUND: The management of pregnant women with anti-Jsb is challenging due to the paucity of antigen-negative blood for fetal and neonatal transfusion. CASE REPORT: A 29-year-old woman with anti-Jsb was referred for assessment of recurrent fetal losses. With the presence of the sister as a historically matched donor, she was planned for active surveillance for fetal anemia during pregnancy. STUDY DESIGN AND METHODS: The fetus remained well until 21 weeks of gestation when signs of fetal anemia and early hydrops fetalis were noted. Anti-Jsb titer was at 128. The sister's red blood cells (RBCs) were cross-match incompatible. Urgent intrauterine transfusion (IUT) was performed with washed irradiated maternal RBCs, donated after cessation of heparin. The mother was given intravenous iron (IV-Fe) and continued on weekly recombinant human erythropoietin (rHu-EPO). RESULTS: Repeated IUTs were needed every 1 to 3 weeks. Throughout a 7-week period, three maternal donations were performed with total donated whole blood volume of 1250 mL, supporting four IUTs. At 29 weeks of gestation, the procedure was complicated by umbilical cord hematoma necessitating urgent cesarean section. A male newborn was delivered, transfused at birth, and subsequently treated with phototherapy and five top-up transfusions. CONCLUSION: This case represents a successful example of managing hemolytic disease of the fetus due to a rare antibody using maternal blood. It also supports previous data on safety of maternal donations during pregnancy and the use of combination of rHu-EPO and IV-Fe as a supportive measure.

Genital ulcer development in patients with acute promyelocytic leukaemia treated with all-trans retinoic Acid: a case series.

We report here four cases of genital ulcers that developed after the administration of all-trans retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia (APL). Between October 2007 and March 2010, three males and one female (age range 19-35 years) were identified to have genital ulcers after being prescribed all-trans retinoic acid (ATRA) as a part of chemotherapy for APL. This is the first series of cases describing genital ulcers, as a unique and rare complication of ATRA used for treatment of APL in these patients, with no other cause identified. Following temporary cessation of ATRA for a few days in these three cases, improvement of the ulcers was noted.

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.