A pioneer experience in Malaysia on In-house Radio-labelling of 131I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose 131I-rituximab-BEAM conditioning autologous transplant

Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies – 90Y-ibritumomab tiuxetan is expensive and 131I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling 131I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling 131I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose 131I-rituximab (6000 MBq/163 mCi) combined with BEAM conditioning for autologous HSCT

In-House Radio-Labelling Of 131i-Rituximab In Threatment Of Cd20+ B-Cell Non-Hodgkin’s Lymphoma: A Pioneer Experience In Malaysia

Background Radioimmunotherapy (RIT) is an established treatment modality in Non-Hodgkin’s lymphoma (NHL). The only two commercially available RITs - 90Y-ibritumomab tiuxetan (Zevalin®) is expensive and 131I-tositumomab has been discontinued from commercial production. In resource limited environment, 90Y-ibritumomab tiuxetan and autologous haematopoietic stem cell transplantation (HSCT) might not be possible. Self-labelling 131I-rituximab might be the only viable practical option. There is no randomized controlled trial comparing RIT versus autologous HSCT in NHL to examine the possibility of RIT substituting autologous HSCT. We reported our pioneer experience in Malaysia on self-labelling 131I-rituximab, substituting autologous HSCT and a patient, whom to our knowledge, is the first reported case received high dose 131I-rituximab (6000 MBq or 163 mCi) combined with BEAM conditioning for autologous HSCT. Clinical Presentation Six patients (Diffuse Large B-cell Lymphoma (DLBCL) (n = 4), Follicular Lymphoma (FL) grade 2 (n = 2)), who were primary refractory/progressive except one and indicated but unable to receive autologous HSCT, and one primary refractory and progressive Primary Mediastinal (thymic) Large B-cell Lymphoma (PMBL), median age 60 (range 26-62), M:F = 6;1, received self-labelling 131I-rituximab from August to October 2014. Six patients received the usual dosage and one patient with PMBL received high dose combined with BEAM conditioning autologous HSCT. Median follow-up was 15.5 months (range 12.5-16.5). They achieved complete response (CR) (except PMBL - partial response (PR)) as the best response. At the latest follow-up, all the DLBCL remained in CR, one FL had slow progressive disease not symptomatic nor requiring intervention, one FL died after three months of 131I-rituximab due to rectal papillary mucinous adenocarcinoma which was symptomatic and diagnosed after 131I-rituximab, and the PMBL remained in PR. In our very limited experience young patients age less than 60 tolerated the treatment well without grade 4 neutropaenia or thrombocytopaenia. Three out of four elderly patients age 60 or above developed grade 4 haematoloigcal toxicity, which might be related to undiagnosed bone marrow infiltration because two of them had FL. Except for the patient who had developed rectal carcinoma and pre-existing myelodysplastic syndrome (MDS), none developed febrile neutropaenia or required antibiotics. None developed hypothyroidism, myelodysplastic syndrome or acute myeloid leukaemia, albeit follow-up is still short. Intervention (& Technique) The usual dosage: 5 mCi on Day 0 (dosimetry dose) and total-body dose 0.75 Gy on Day 7 (therapeutic dose). High dose: 6000 MBq (163 mCi) on Day -18 combined with BEAM conditioning, started on Day -8, for autologous HSCT. Discussion/Conclusion Self-labelled 131I-rituximab may be a viable option to substitute autologous HSCT in refractory/relapse NHL, especially when autologous HSCT is not feasible. It is is definitely cheaper and halves the cost of Zevalin®. Its use in PMBL warrants further study

Comparison of Mortality Outcomes in Acute Myocardial Infarction Patients With or Without Standard Modifiable Cardiovascular Risk Factors

Background: Acute myocardial infarction (AMI) cases have decreased in part due to the advent of targeted therapies for standard modifiable cardiovascular disease risk factors (SMuRF). Recent studies have reported that ST-elevation myocardial infarction (STEMI) patients without SMuRF (termed "SMuRF-less") may be increasing in prevalence and have worse outcomes than "SMuRF-positive" patients. As these studies have been limited to STEMI and comprised mainly Caucasian cohorts, we investigated the changes in the prevalence and mortality of both SMuRF-less STEMI and non-STEMI (NSTEMI) patients in a multiethnic Asian population. Methods: We evaluated 23,922 STEMI and 62,631 NSTEMI patients from a national multiethnic registry. Short-term cardiovascular and all-cause mortalities in SMuRF-less patients were compared to SMuRF-positive patients. Results: The proportions of SMuRF-less STEMI but not of NSTEMI have increased over the years. In hospitals, all-cause and cardiovascular mortality and 1-year cardiovascular mortality were significantly higher in SMuRF-less STEMI after adjustment for age, creatinine, and hemoglobin. However, this difference did not remain after adjusting for anterior infarction, cardiopulmonary resuscitation (CPR), and Killip class. There were no differences in mortality in SMuRF-less NSTEMI. In contrast to Chinese and Malay patients, SMuRF-less patients of South Asian descent had a two-fold higher risk of in-hospital all-cause mortality even after adjusting for features of increased disease severity. Conclusion: SMuRF-less patients had an increased risk of mortality with STEMI, suggesting that there may be unidentified nonstandard risk factors predisposing SMuRF-less patients to a worse prognosis. This group of patients may benefit from more intensive secondary prevention strategies to improve clinical outcomes

Association between smoking status and outcomes in myocardial infarction patients undergoing percutaneous coronary intervention

Smoking is one of the leading risk factors for cardiovascular diseases, including ischemic heart disease and hypertension. However, in acute myocardial infarction (AMI) patients, smoking has been associated with better clinical outcomes, a phenomenon termed the “smoker’s paradox.” Given the known detrimental effects of smoking on the cardiovascular system, it has been proposed that the beneficial effect of smoking on outcomes is due to age differences between smokers and non-smokers and is therefore a smoker’s pseudoparadox. The aim of this study was to evaluate the association between smoking status and clinical outcomes in ST-segment elevation (STEMI) and non-STEMI (NSTEMI) patients treated by percutaneous coronary intervention (PCI), using a national multi-ethnic Asian registry. In unadjusted analyses, current smokers had better clinical outcomes following STEMI and NSTEMI. However, after adjusting for age, the protective effect of smoking was lost, confirming a smoker’s pseudoparadox. Interestingly, although current smokers had increased risk for recurrent MI within 1 year after PCI in both STEMI and NSTEMI patients, there was no increase in mortality. In summary, we confirm the existence of a smoker’s pseudoparadox in a multi-ethnic Asian cohort of STEMI and NSTEMI patients and report increased risk of recurrent MI, but not mortality, in smokers

Association of body mass index, metabolic health status and clinical outcomes in acute myocardial infarction patients: a national registry-based study

IntroductionObesity is an important risk factor for acute myocardial infarction (AMI), but the interplay between metabolic health and obesity on AMI mortality has been controversial. In this study, we aimed to elucidate the risk of short- and long-term all-cause mortality by obesity and metabolic health in AMI patients using data from a multi-ethnic national AMI registry.MethodsA total of 73,382 AMI patients from the national Singapore Myocardial Infarction Registry (SMIR) were included. These patients were classified into four groups based on the presence or absence of metabolic diseases, diabetes mellitus, hyperlipidaemia, and hypertension, and obesity: (1) metabolically-healthy-normal-weight (MHN); (2) metabolically-healthy-obese (MHO); (3) metabolically-unhealthy-normal-weight (MUN); and (4) metabolically-unhealthy-obese (MUO).ResultsMHO patients had reduced unadjusted risk of all-cause in-hospital, 30-day, 1-year, 2-year, and 5-year mortality following the initial MI event. However, after adjusting for potential confounders, the protective effect from MHO on post-AMI mortality was lost. Furthermore, there was no reduced risk of recurrent MI or stroke within 1-year from onset of AMI by the MHO status. However, the risk of 1-year mortality was higher in female and Malay AMI patients with MHO compared to MHN even after adjusting for confounders.ConclusionIn AMI patients with or without metabolic diseases, the presence of obesity did not affect mortality. The exception to this finding were female and Malay MHO who had worse long-term AMI mortality outcomes when compared to MHN suggesting that the presence of obesity in female and Malay patients may confer worsened outcomes

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

Association of body mass index, metabolic health status and clinical outcomes in acute myocardial infarction patients: a national registry-based study

10.3389/fcvm.2023.1142078FRONTIERS IN CARDIOVASCULAR MEDICINE1

Comparison of Mortality Outcomes in Acute Myocardial Infarction Patients With or Without Standard Modifiable Cardiovascular Risk Factors

10.3389/fcvm.2022.876465FRONTIERS IN CARDIOVASCULAR MEDICINE

Comparison of the modified Singapore myocardial infarction registry risk score with GRACE 2.0 in predicting 1-year acute myocardial infarction outcomes

10.1038/s41598-022-16523-6SCIENTIFIC REPORTS12