Immune reconstitution and survival, following hematopoietic stem cell transplantation in Omani patients with inborn errors of immunity.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for certain inborn errors of immunity. METHODS: A 17-year retrospective cohort study was conducted on 40 immunodeficient patients who underwent HSCT. RESULTS: The median age at transplant was 11.0 months (4.6-61.0). Donors were primarily matched sibling donors (60%). 90% and 85% of patients received conditioning and graft-versus-host disease (GVHD) prophylaxis, respectively. The mean donor chimerism at the last follow-up was 88.6% ± 17.9% (40-100). Median serum immunoglobulin (Ig) G level, CD4+ T-cell count, and CD19+ B-cell count were 11.7 g/L (9.2-13.6), 0.9 × 109/L 0.6-1.2), and 0.5 × 109/L (0.2-0.7), respectively. 29 patients (72.5%) received intravenous immunoglobulins (IVIG) therapy, with a median duration of 10.0 months (4.0-14.0). The median post-transplant follow-up was 6.5 years (IQR:1.4-11.5). The 10-year overall probability of survival is 84.3%. CONCLUSION: Monitoring IRC is important in ensuring adequate disease-free survival.

Real-World Registry on the Pharmacotherapy of Multiple Myeloma and Associated Renal and Pulmonary Impairments in the Greater Gulf Region: Protocol for a Retrospective Real-World Data Study.

BACKGROUND: Multiple myeloma (MM) is the second-most common cancer among hematological malignancies. Patients with active disease may experience several comorbidities, including renal insufficiency and asthma, which may lead to treatment failure. The treatment of relapsed or refractory MM (RRMM) has been associated with multiple factors, causing a decline in progression-free survival as well as overall survival with subsequent lines of therapy. Data about the characteristics of this group of patients in the Greater Gulf region are lacking. OBJECTIVE: The primary objective of this study is to describe the disease characteristics and various treatment approaches or regimens used in the management of patients with RRMM in the Greater Gulf region. METHODS: We will conduct a regional, retrospective study collecting real-world and epidemiological data on patients with MM in countries of the Greater Gulf region. Medical records will be used to obtain the required data. Around 150 to 170 patients' records are planned to be retrospectively reviewed over 6 months without any cross-sectional or prospective intervention. Cases will be collected from Saudi Arabia, the United Arab Emirates, Kuwait, Oman, and Qatar. Descriptive as well as analytical statistics will be performed on the extracted data. The calculated sample size will allow us to estimate the percentages of RRMM cases with acceptable precision while complying with the challenges in light of data scarcity. We will obtain a comprehensive description of the demographic profile of patients with MM; treatment outcomes; the proportion of patients with MM with renal impairment and asthma, chronic obstructive pulmonary disease, or both at the time of diagnosis and any subsequent point; and data related to treatment lines, regimens, and MM-associated morbidities. RESULTS: Patient medical records were reviewed between June 2022 and January 2023 for eligibility and data extraction. A total of 148 patients were eligible for study inclusion, of whom 64.2% (n=95) were male and 35.8% (n=53) were female. The study is currently in its final stages of data analysis. The final manuscript is expected to be published in 2024. CONCLUSIONS: Although MM is a predominant hematological disease, data on its prevalence and patients' characteristics in the Greater Gulf region are scarce. Therefore, this study will give us real-world insights into disease characteristics and various management approaches of patients with MM in the Greater Gulf region. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49861.

Evidence-based Management of Chronic Lymphocytic Leukemia: Consensus Statements from the Gulf Region.

INTRODUCTION: Despite recent advances in diagnosis, prognostication, and treatment options, chronic lymphocytic leukemia (CLL) is still a largely incurable disease. New concepts on diagnosis, staging, treatment, and follow-up on CLL have been incorporated throughout recent years. The lack of regional consensus guidelines has led to varying practices in the management of patients with CLL in the region. AIM: This manuscript aims to reach a consensus among expert hematologists regarding the definitions, classifications, and related practices of CLL. The experts developed a set of statements utilizing their personal experience together with the current literature on CLL management. This consensus aims to provide guidance for healthcare professionals involved in the management of CLL and serves as a step in developing regional guidelines. METHODS: Eight experts responded to 50 statements regarding the diagnosis, staging, treatment, and prognosis of CLL with three potential answering alternatives ranging between agree, disagree, and abstain. This consensus adopted a modified Delphi consensus methodology. A consensus was reached when at least 75% of the agreement to the answer were reached. This manuscript presents the scientific insights of the participating attendees, panel discussions, and the supporting literature review. RESULTS: Of the 50 statements, a consensus was reached on almost all statements. Statements covered CLL-related topics, including diagnostic evaluation, staging, risk assessment, different patient profiles, prognostic evaluation, treatment decision, therapy sequences, response evaluation, complications, and CLL during the COVID-19 pandemic. DISCUSSION/CONCLUSION: In recent years, CLL management has progressed significantly with many diagnostic tests and several novel treatments becoming available. This consensus gathers decades of consolidated principles, novel research, and promising prospects for the management of this disease.

Clinical course and outcomes of COVID-19 in hematopoietic cell transplant patients, a regional report from the Middle East.

The coronavirus disease-2019 (COVID-19) caused by SARS Coronavirus 2 (SARS-CoV-2) is a potentially lethal infection. Cancer patients, and specifically hematopoietic cell transplant (HCT) recipients are severely immunocompromised and may be at a higher risk of a complicated course with this infection. We aimed to study the COVID-19 outcomes and severity in post HCT patients. We retrospectively reviewed post-HCT patients diagnosed with COVID-19 between March 15, 2020, and December 1, 2020 at 10 transplant centers across the Middle East. We identified 91 patients with confirmed SARS-CoV-2 infection across 10 transplant centers. The median age upon presentation with COVID-19 was 35. Fifty two patients were post allo-HCT while the remaining 39 patients were post auto-HCT. The median time from transplant was 14.9 months. Mortality rate was 4.4%. Hospital admission rate was 53%. ICU admission rate was 14%. Mechanical ventilation rate was 10%. Oxygen supplementation rate was 18%. Time from HCT to COVID-19 >6 months was associated with lower admission rates and lower rates of the "severity" composite endpoint. Antibody responses was seen 67% of evaluable patients. In this series of HCT recipients, we report overall favorable clinical outcomes for patients with COVID-19 and provide preliminary insights into the clinical course of this disease in this specific population.

Efficiency of day 4 compared to day 6 stem cell mobilization in allogeneic stem cell donors.

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) given for 4-6 days is commonly used for mobilization of allogeneic stem cell donors. The primary objective of this study is to compare the yield of stem cell mobilization, assessed using a surrogate endpoint of CD34+ cell count, between Day 4 and Day 6. STUDY DESIGN AND METHODS: In this retrospective study we included all allogeneic stem cell donors mobilized with G-CSF for 6 days from January 2003 until October 2015 in the bone marrow transplantation unit at a tertiary academic center. Of 106 donor records reviewed, 84 were with available data and selected for the study. RESULTS: We included 84 donors with median age and weight of 19 years and 60 kg respectively. The median Day 4 WBC and CD34+ cell count were 37.4 × 109/L and 54 × 106/L respectively; while the median Day 6 WBC and CD34+ cell count were 44.4 × 109/L and 86 × 106/L respectively with a statistically significant difference from Day 4 (P < 0.001). In the multivariable model, there were no significant impact of donor's age (P = 0.215), weight (P = 0.108), height (P = 0.428) and mean corpuscular volume (P = 0.263) on the difference in CD34+ cell yield. However, the donor's blood group AB predicated a significantly higher difference (P = 0.036). CONCLUSION: Six days of G-CSF mobilization achieves higher CD34+ cell count than 4 days in allogeneic stem cell donors especially in donors with blood group AB, albeit both approaches give count higher than the successful collection threshold.

Levels of regulatory T cells and invariant natural killer cells and their associations with regulatory B cells in patients with non-Hodgkin lymphoma.

Due to their immunoregulatory properties, several specialized cell subsets, including regulatory T (Treg), invariant natural killer T (iNKT) and regulatory B (Breg) cells, are involved in the pathogenesis of non-Hodgkin lymphoma (NHL). However, the interaction between various cells remains to be elucidated. The aim of the present study was to evaluate the levels of Treg, iNKT and Breg cell subsets and their interrelationships in the peripheral blood (PB) and bone marrow (BM) of patients with B-cell NHL who received rituximab-based regimens and achieved a complete remission. A total of 20 patients and 20 healthy age- and sex-matched controls were prospectively enrolled for investigation of Treg, iNKT and Breg cell subsets in PB and BM by flow cytometry and cell culture. Prior to administration of combination chemotherapy with rituximab, the patients had lower levels of Breg cells and, to a lesser degree, Treg cells, but not iNKT cells, in PB compared with controls. Compartmental differences in the levels of Treg and Breg cell subsets, but not iNKT cells, were observed between PB and BM, suggesting an increase in trafficking through the blood of these regulatory cell subsets to the marrow. Following complete remission, the levels of circulating Treg, iNKT and Breg cell subsets increased. The levels of Treg cells were not significantly associated with iNKT and Breg cell subsets, although negative correlations were observed. Taken together, these results may provide new insights into the potential role of regulatory cell subsets in patients with B-cell NHL. However, whether the observed differences between PB and BM may affect clinical outcomes requires further investigation.

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.

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.

Relapse of Multiple Myeloma Presenting as Lower Lip Numbness.

Multiple myeloma (MM) is an uncommon malignancy characterised by the proliferation of clonal plasma cells. There are few published reports describing the extramedullary presentation of MM manifesting primarily in the head and neck region. In addition, the occurrence of an isolated relapse of MM in these sites is exceedingly rare. We report a 56-year-old female who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2010 with sudden-onset numbness of the lower lip. She had a history of MM in remission following chemotherapy and a bone marrow transplant. Clinical and radiographic examinations were indicative of a possible relapse of MM, which was subsequently confirmed by bone marrow aspiration and histopathological evaluation. This unique case highlights the unusual site of relapse of a haematolymphoid malignancy.

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.

Aetiological profile of women presenting with premature ovarian failure to a single tertiary care center in Oman.

BACKGROUND: Premature ovarian failure is estimated to affect at least 1%-3% of adult women. There are several aetio-pathogenic factors that may cause premature ovarian failure including iatrogenic causes, genetic, autoimmune, infectious and idiopathic. The aim of this study was to identify the aetiological profile of women with premature ovarian failure presenting to Sultan Qaboos University hospital. METHOD: A retrospective medical record review was conducted from June 2006 to October 2012. All women diagnosed with symptoms and/or laboratory evidence of premature ovarian failure (follicle stimulating hormone ≥40 UI/L and less than 40 years of age) were enrolled in this study. Possible causes of premature ovarian failure were obtained and classified into main aetiological factors. RESULTS: There were 90 patients during the study period, of which, 39 (43%) were following chemotherapy and bone marrow transplant. The second most common reason was idiopathic (n = 29; 31%) followed by autoimmune diseases (n = 8; 9%) and genetic disorders (n = 7; 8%). Most chemotherapy cases (69%) were among the young age group, while in the older age group idiopathic was the commonest (48%). CONCLUSION: Compared to the world literature, the most common cause of premature ovarian failure in this study was chemotherapy induced, especially in young girls undergoing bone marrow transplantation. This is due to high prevalence of transplantable hereditary haematological disorders like thalassemia and sickle-cell disease in this part of the world. Current standard of care recommends cryopreservation of ovarian tissue to preserve ovarian function in young girls undergoing bone marrow transplantation for such disorders.

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.

A study on knowledge, attitude, and practice towards premarital carrier screening among adults attending primary healthcare centers in a region in Oman.

BACKGROUND: Despite that hereditary diseases are widespread among the Arab population due to high rates of consanguineous marriages, research regarding community awareness towards premarital carrier screening in some countries such as Oman, is extremely scarce. This study aimed to investigate knowledge and attitude towards premarital carrier screening (PMCS) in Oman. METHODS: A cross-sectional study was conducted using a self-administered questionnaire which was distributed to 400 Omani adults aged 20-35 who attended primary healthcare institutions at the South Batinah Governorate in Oman. RESULTS: The majority of the participants (84.5%) believed that PMCS was necessary, and about half of them (49.5%) supported the view of making PMCS compulsory. On the contrary, approximately one third (30.5%) of the participants reported that they were not in favor of taking the blood screening test. Overall, unwillingness to perform pre-marital testing was associated with female gender, younger age, being single, less education, and increased income. CONCLUSION: Despite the relatively high level of knowledge, about one third of the participants were still reluctant to carry out premarital testing. Such attitude calls for immediate need for community-based campaigns to encourage the public to do premarital testing.

Methemoglobinemia in an elderly patient with glucose-6-phosphate dehydrogenase deficiency: a case report.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder characterized by low levels of the G6PD enzyme. It is present worldwide but with more prevalence in the Middle East and the Mediterranean areas. We report a case of severe hemolysis due to G6PD deficiency manifesting as methemoglobinemia in a 70 year old Omani male never known to have any previous hemolytic episodes or previously diagnosed of G6PD deficiency.