The Sarawak Myelofibrosis (SaMy) experience: Demographics and outcome of myelofibrosis patients in Sarawak, Malaysia.

Introduction: Myelofibrosis is a rare disease. There is currently no published data reporting the demographics and outcome of myelofibrosis patients in Malaysia. We aimed to study the demographics, clinical characteristics, and outcome of our patients in Sarawak. Materials and methods: This non-interventional, retrospective, and multi-center study was conducted on secondary data of medical records collected at four Sarawak Public Hospitals. All adult myelofibrosis patients diagnosed between January 2001 and December 2021 were included. Results: A total of 63 patients (male 31) with myelofibrosis were included-47 (74.6%) primary and 16 (25.4%) secondary myelofibrosis. Eleven had antecedent polycythaemia vera, whereas five transformed from essential thrombocythaemia. The combined annual incidence rate was 0.182 per 100,000 population. The period prevalence per 100,000 population over the entire study duration was 2.502. The median age was 59.0 years (33.0-93.0). Majority had high-risk (34/63(54.0%)) and intermediate-2 risk disease (19/63(30.2%)). JAK2V617F mutation was identified in 52 patients (82.5%), followed by CALR mutation in 6 (9.5%) and negative for both mutations in 5 (7.9%). Hydroxyurea was used as first-line therapy in 41/63 (65.1%), followed by interferon (8/63(12.7%)) and ruxolitinib (4/63(6.3%)). Out of 46 patients who received second-line therapy, 18 (39.1%) were switched to ruxolitinib and 9 (19.6%) to interferon. The median age of survival for overall patients was 6.8 years. The use of ruxolitinib in myelofibrosis patients showed a better overall 5-year survival compared to the no ruxolitinib arm, despite no statistical significance (p = 0.34). Patients who had good performance status had lower hazard of death than patients who had poor performance status (high-risk (95% confidence intervals): 0.06(0.013-0.239), p < 0.001). Patients with intermediate risk disease had better overall survival compared to those in high-risk group (95% confidence intervals): 0.24(0.082-0.695), p = 0.009). Conclusion: This registry provides a real-world overview of myelofibrosis patients in our state and highlights the key insight into the unmet clinical need.

Secondary hemophagocytic lymphohistiocytosis: an unusual complication in disseminated Mycobacterium tuberculosis.

Tuberculosis-associated hemophagocytic lymphohistiocytosis (TB-HLH) is a rare and life-threatening complication of tuberculosis infection. Early recognition and treatment of TB-HLH is crucial for improving outcomes. Treatment typically involves a combination of antituberculosis therapy and immunosuppressive therapy to control the immune system's overreaction. In this report, we present the case of a 53-year-old ambulance driver who was diagnosed with TB-HLH. His CT scan revealed splenic abscesses, hepatomegaly and bilateral lung consolidation. He subsequently developed multiorgan failure, including acute respiratory distress syndrome (ARDS), transaminitis and bone marrow dysfunction. The clinical course and simultaneous increase in serum ferritin raised the suspicion of HLH. His Hscore was 254, indicating a high probability of hemophagocytic syndrome. TB diagnosis was confirmed by positive endotracheal TB GeneXpert and bone marrow aspiration (BMA) which detected acid-fast bacilli organisms. The patient was promptly started on anti-TB, dexamethasone and IVIG. The patient responded well to treatment and made a full recovery without any lasting complications. This case highlights the importance of promptly recognising HLH and identifying the underlying cause. In critically ill patients, it is crucial not to delay HLH-specific treatment while working up for differential diagnosis.

Cost of Treatment for Myelofibrosis Patients in Ministry of Health Hospitals in Sarawak, Malaysia.

OBJECTIVE: Primary myelofibrosis is a rare type of myeloproliferative neoplasm with an annual incidence rate of 0.47 per 100,000. A retrospective, observational study was conducted to determine the disease evolution and costs of treatment for myelofibrosis (MF) patients managed in 4 Ministry of Health (MOH) hospitals in Sarawak, Malaysia. METHODS: The estimation of treatment cost was a planned analysis of the Real World Evidence (RWE) study which included retrospective chart review of adult MF patients treated in Sarawak General, Sibu, Bintulu and Miri Hospitals. The study was approved by Sarawak General Hospital HRRC and MREC. The current study was conducted to estimate the cost of out-patient visits, hospitalisation, transfusion and medication from the perspective of MOH. Out-patient visits and hospitalisation costs were calculated using current unit costs for full fee-paying charges of MOH hospitals. Transfusion costs were estimated for packed cell and platelet transfusions. Medication costs were calculated using drug prices from IQVIA database for MOH hospital sub-sector in 2021. Unit costs were standardised to index year of 2021. RESULT: Data from 63 patients was available for analysis. Mean annual health resource utilisation (HRU) was 6.13 clinic visits, 9.47 days of hospitalisation and 1.61 transfusions per patient per year. Mean HRU cost was RM23,320 (USD5,217) per patient per year, comprised of RM19,122 (USD4,278) in drug costs, RM3,030 (USD678) for hospitalisation, RM799 (USD178) for transfusions and RM368 (USD82) for outpatient cost. CONCLUSION: The present analysis suggests that medication and hospitalisation were the main drivers of costs for MF treatment in Sarawak MOH hospitals. This study provides the first RWE estimate of the cost of MF in Malaysia and may provide insight into unmet clinical needs and a guide for further health economic research into the treatment of MF.

Clinical Epidemiology, Treatment Outcome and Mortality Rate of Newly Diagnosed Immune Thrombocytopenia in Adult Multicentre Study in Malaysia.

Background: Immune thrombocytopenia (ITP) is well characterized in Western, European and other Asia-Pacific countries. Nevertheless, the clinical epidemiology, treatment pattern and disease outcome of ITP in Malaysia are still limited and not well known. Objective: This study aimed to describe the clinical epidemiology, treatment outcome and mortality of ITP patients in haematology tertiary multicentre in Malaysia. Methods: Clinical and laboratory data of newly diagnosed adults with ITP by a platelet count <100 × 109/L from January 2010 to December 2020 were identified and analyzed. Results: Out of 500 incident ITP, 71.8% were females with a striking age preponderance of both genders among those aged 18-29 years. The median age was 36 years. The median platelet count was 17.5 × 109/L, 23.0% had a secondary ITP, 34.6% had a Charlson's score ≥1, 53.0% had bleeding symptoms including 2.2% intracranial bleedings (ICB). Helicobacter pylori screening was performed in <5% of cases. Persistency and chronicity rates were 13.6% and 41.8%, respectively. Most (80.6%) were treated at diagnosis onset and 31.2% needed second-line treatment. Throughout the course of ITP, 11.0% of patients died; 3.0% and 8.0% with bleeding and non-bleeding related ITP. Conclusion: This study confirms the epidemiology of ITP is comparable with worldwide studies. Our incidence is high in the female, Malay ethnicity, primary ITP and events of cutaneous bleeding at ITP onset with 18-29 years predominance age group for both genders. The frequency of persistent and chronic ITP is inconsistent with published literature. Corticosteroids and immunotherapies are the most prescribed first-line and second-line pharmacological treatments. Thrombopoietin receptor agonist medications (TPO-RAs) usage is restricted and splenectomy is uncommon. Our mortality rate is similar but ITP related bleeding death is fourth-fold lower than previous studies. Mortality risks of our ITP patients include age ≥60 years, male, severe bleeding at presentation, CCI≥1 and secondary ITP.

Trichobezoar masquerading as massive splenomegaly: Rapunzel's syndrome revisited.

Trichobezoars are usually formed due to ingestion of hair or hair-like fibres and present with a wide spectrum of clinical manifestations. We report a case of Rapunzel's syndrome associated with trichotillomania in a 16-year-old girl who presented to our Haematology unit with complaints of fatigue, abdominal distention, and early satiety. Initial evaluation demonstrated anaemia, thrombocytosis, and a left hypochondrial mass suggestive of splenomegaly. However, ultrasound of the abdomen showed no hepatosplenomegaly and blood investigations were not suggestive of haematological malignancy. Not long after, the patient presented to the emergency department with suspected acute abdomen. Computed tomography of the abdomen revealed intraluminal gastric and jejunal masses causing small bowel obstruction. Emergency laparotomy confirmed gastric and jejunal trichobezoars, and subsequent psychiatric evaluation confirmed trichotillomania. Clinicians should consider trichobezoar in the differential diagnosis of abdominal pain and a non-tender 'spleen-like' abdominal mass.

A family of three with haemoglobin Cheverly: low oxygen saturation in stable patients.

Haemoglobin (Hb) Cheverly is a rare, low oxygen affinity haemoglobinopathy. It is a result of point mutation at the 45 codon of the beta globin genes that leads to substitution of phenylalanine by serine. It is characterised by spuriously low peripheral oxygen saturation with normal arterial oxygen saturation. We describe a family of three with Hb Cheverly in Sarawak General Hospital, Malaysia. It was discovered through incidental finding during hospital admission for unrelated complaints. Laboratory testing revealed abnormal haemoglobin detected at the C window of the high performance liquid chromatography. Subsequent DNA analysis detected replacement of thymidine by cytosine at the beta globin genes. Hb Cheverly may or may not have clinical significance as most of the patients live a normal life; however, it is crucial for us to make early diagnosis to prevent unnecessary extensive investigations for hypoxaemia detected via pulse oximetry, especially in the midst of COVID-19 pandemic.

Impact of timely BCR-ABL1 monitoring before allogeneic stem cell transplantation among patients with BCR-ABL1-positive B-acute lymphoblastic leukemia.

BACKGROUND: With the emergence of tyrosine kinase inhibitors and the incorporation of stringent measurable residual disease (MRD) monitoring, risk stratification for BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients has changed significantly. However, whether this monitoring can replace conventional risk factors in determining whether patients need allogeneic stem cell transplantation is still unclear. This study aimed to determine the impact of BCR-ABL1 monitoring on the outcome of patients with BCR-ABL1-positive ALL after allogeneic stem cell transplantation. METHODS: We retrospectively analyzed the survival outcome of patients with BCR-ABL1-positive ALL based on the quantification of BCR-ABL1 at 3 timepoints: the end of induction (timepoint 1), post-consolidation week 16 (timepoint 2), and the end of treatment for patients who were either transplant-eligible or non-transplant eligible (timepoint 3). RESULTS: From 2006 to 2018, a total of 96 patients newly diagnosed with BCR-ABL1-positive ALL were treated with chemotherapy and tyrosine kinase inhibitors. Thirty-eight (41.3%) patients achieved complete remission, and 33 patients underwent allogeneic stem cell transplantation. Our data showed that pre-transplant MRD monitoring by real-time quantitative polymerase chain reaction had the highest correlation with survival in patients with BCR-ABL1-positive ALL, especially for those who underwent allogeneic stem cell transplantation. CONCLUSION: Patients without MRD pre-transplantation had superior survival compared with those who had MRD, and they had excellent long-term outcomes after allogeneic stem cell transplantation.

Successful Non-surgical Treatment of an Acute Calculous Cholecystitis in a Myeloma Patient with Covid-19: Case Report.

COVID-19 has a wide spectrum of clinical phenotypes. While fever and cough are the most common symptoms, abdominal pain is rarely reported. We report the first case of COVID-19 pneumonia in an elderly patient with multiple myeloma (MM), complicated by acute calculous cholecystitis (ACC). A 73-year-old gentleman with underlying IgG kappa MM, presented with fever, cough and dyspnoea. His nasopharyngeal swab was positive for SARS-CoV-2. Piperacillin/tazobactam and oral hydroxychloroquine were started in addition to granulocyte colony-stimulating factor (GCSF) support due to neutropenia. Patient deteriorated on day 5, requiring high flow oxygen support. Dexamethasone, low molecular weight heparin prophylaxis and one dose of intravenous immunoglobulin were given. Despite negative swab on day 10, he developed ACC on day 17. With antibiotics and supportive care, patient showed full recovery without any surgical intervention. It remains elusive whether the gallbladder might be vulnerable to COVID-19, necessitating further validation via prospective studies.

Correction to: Thrombosis and Bleeding as Presentation of COVID-19 Infection with Polycythemia Vera: a Case Report.

[This corrects the article DOI: 10.1007/s42399-020-00537-0.].

Thrombosis and Bleeding as Presentation of COVID-19 Infection with Polycythemia Vera. A Case Report.

Coronavirus disease (COVID-19) has a wide spectrum of clinical manifestations. In this case report, we describe our first case of COVID-19 pneumonia that was complicated by cerebral venous thrombosis and bleeding in a patient with polycythemia vera. Madam A, a 72-year-old lady with polycythemia vera, ischemic stroke, hemorrhoids, diabetes mellitus, hypertension, and dyslipidemia was admitted to the hospital for COVID-19 pneumonia. She was treated with hydroxychloroquine and lopinavir/ritonavir as per hospital protocol. She continued taking hydroxyurea and aspirin for her treatment of polycythemia vera. Subsequently, she developed rectal bleeding when her platelet count was 1247 × 103/µl, even though she was not on an anticoagulant. Her aspirin was withheld. One week later, she was readmitted to the hospital for cerebral venous thrombosis and her D-dimer was 2.02 µg/ml. She was commenced on a therapeutic dose of low molecular weight heparin. Following that, her D-dimer level showed a decreasing trend and normalized upon her discharge. Patients with polycythemia vera are prone to develop thrombotic and bleeding complications. Management of this group of patients has become more complex with COVID-19 infection. It is crucial for us to decide when to start an anticoagulant especially when there is a history of recent bleeding. We need to balance the risks of further bleeding versus potentially fatal thrombotic events. Studies have shown that D-dimer can be used as a clinical marker to predict thrombotic events in COVID-19 infection. Patients with COVID-19 infection and polycythemia vera will benefit from both pharmacological thromboprophylaxis and close monitoring for bleeding.

Low-molecular-weight heparins or heparinoids versus standard unfractionated heparin for acute ischaemic stroke.

BACKGROUND: Low-molecular-weight heparins (LMWHs) and heparinoids are anticoagulants that may have more powerful antithrombotic effects than standard unfractionated heparin (UFH) but a lower risk of bleeding complications. This is an update of the original Cochrane Review of these agents, first published in 2001 and last updated in 2008. OBJECTIVES: To determine whether antithrombotic therapy with LMWHs or heparinoids is associated with a reduction in the proportion of people who are dead or dependent for activities in daily living compared with UFH. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched February 2017), the Cochrane Central Register of Controlled Trials (CENTRAL: the Cochrane Library Issue 1, 2017), MEDLINE (1966 to February 2017), and Embase (1980 to February 2017). We also searched trials registers to February 2017: ClinicalTrials.gov, EU Clinical Trials Register, Stroke Trials Registry, ISRCTN Registry and the World Health Organization (WHO) International Clinical Trials Registry Platform. SELECTION CRITERIA: Unconfounded randomised trials comparing LMWH or heparinoids with standard UFH in people with acute ischaemic stroke, in which participants were recruited within 14 days of stroke onset. DATA COLLECTION AND ANALYSIS: Two review authors independently chose studies for inclusion, assessed risk of bias and trial quality, extracted and analysed the data. Differences were resolved by discussion. MAIN RESULTS: We included nine trials involving 3137 participants. We did not identify any new trials for inclusion in this updated review. None of the studies reported data on the primary outcome in sufficient detail to enable analysis for the review. Overall, there was a moderate risk of bias in the included studies. Compared with UFH, there was no evidence of an effect of LMWH or heparinoids on death from all causes during the treatment period (96/1616 allocated LMWH/heparinoid versus 78/1486 allocated UFH; odds ratio (OR) 1.06, 95% CI 0.78 to 1.47; 8 trials, 3102 participants, low quality evidence). LMWH or heparinoid were associated with a significant reduction in deep vein thrombosis (DVT) compared with UFH (OR 0.55, 95% CI 0.44 to 0.70, 7 trials, 2585 participants, low quality evidence). However, the number of the major clinical events such as pulmonary embolism (PE) and intracranial haemorrhage was too small to provide a reliable estimate of the effects. AUTHORS' CONCLUSIONS: Treatment with a LMWH or heparinoid after acute ischaemic stroke appears to decrease the occurrence of DVT compared with standard UFH, but there are too few data to provide reliable information on their effects on other important outcomes, including functional outcome, death and intracranial haemorrhage.