Treatment Pattern and Outcome of Newly Diagnosed Multiple Myeloma Patients in a Resource-Limited Setting.

BACKGROUND: Multiple myeloma is the third most common hematologic malignancy in Malaysia. The introduction of novel agents over the past decades has improved patient outcome and survival substantially. However, these agents incur significant economic burden, thus leading to limited use in less developed countries. This study aims to report on the real-world treatment pattern and outcome of newly diagnosed multiple myeloma (NDMM) patients from a resource-constraint setting. METHODS: This is a retrospective study on NDMM patients diagnosed between 1 January 2008 and 31 December 2022 in a single academic center. Patients' demographic and treatment details were included for analysis of progression free survival (PFS) and overall survival (OS). RESULTS: One hundred and thirty-six NDMM patients with a median age of 64.0 years (ranged from 38 to 87 years old) were included. Bortezomib-containing regimens were the most commonly used induction agent, followed by thalidomide. Almost half of the patients (47.1%) achieved very good partial response (VGPR) or complete remission (CR), while 31.6% achieved partial response (PR). Bortezomib containing regimen was associated with significantly deeper and more rapid response, (p=0.001 and p=0.017, respectively) when compared to other agents. Only 22.8% of these patients proceeded to upfront autologous haematopoietic stem cell transplantation.  The median OS and PFS were 60.0 months and 25.0 months, respectively. Best initial response and upfront autologous stem cell transplantation (ASCT) were significantly associated with better PFS. CONCLUSION: Achieving at least a VGPR significantly associated with better outcome in NDMM patients. In a resource constrain country, we recommend incorporating bortezomib in the induction therapy followed with an upfront ASCT.

CMV Infection Post Allogeneic Hematopoietic Stem Cell Transplantation in a Resource Limited Country.

Cytomegalovirus (CMV) infection is one of the common complications which can lead to significant morbidity and mortality in patients after allogeneic hematopoietic stem cell transplantation (HSCT). As the seroprevalence of CMV infection in Malaysia is high, this study aims to determine the prevalence of CMV infection in patients post HSCT and to evaluate the associated risk factors. Patients who underwent allogeneic HSCT in adult ward from 2008 to 2020 at a tertiary teaching hospital in Kuala Lumpur, Malaysia were studied retrospectively. They were followed up for a minimum of 100 days post-HSCT to determine the incidence of CMV infection. CMV infection was defined according to CMV Drug Development Forum 2014. Risk factors such as type of transplant, serostatus of donor and patients, age, gender, race, presence of graft versus host disease (GVHD) and underlying disease were included for analysis. A total of 112 patients were included. Forty (35.7%) patients had CMV infection with median of onset recorded as 40 days (range 13-95 days). Only haplo-identical HSCT and presence of GVHD were identified as significant risk factors. Patients who had CMV infection had a lower median survival time although this was not statistically significant. The CMV infection rate was comparable with previous reports in Asia and as expected, higher than the western countries. Therefore, vigilant monitoring of CMV infection should be implemented especially in patients who had haplo-identical HSCT and acute GVHD.

KIR genotype and haplotype frequencies in the multi-ethnic population of Malaysia.

Killer cell immunoglobulin-like receptors (KIR) genotype and haplotype frequencies have been reported to vary distinctly between populations, which in turn contributes to variation in the alloreactivity of natural killer (NK) cells. Utilizing the diverse KIR genes to identify suitable transplant donors would prove challenging in multi-ethnic countries, even more in resource-limited countries where KIR genotyping has not been established. In this study, we determined the KIR genotypes from 124 unrelated Malaysians consisting of the Malays, Chinese, Indians, and aboriginal people through polymerase chain reaction sequence-specific primer (PCR-SSP) genotyping and employing an expectation-maximization (EM) algorithm to assign haplotypes based on pre-established reference haplotypes. A total of 27 distinct KIR haplotypes were discerned with higher frequencies of haplotype A (55.2%) than haplotype B (44.8%). The most frequent haplotypes were cA01:tA01 (55.2%), cB01:tB01 (18.1%), and cB02:tA01 (13.3%), while the least frequent haplotypes were cB03:tB01 (1.2%), cB04:tB03 (0.4%), and cB03:tA01 (0.4%). Several haplotypes were identified to be unique to a specific ethnic group. The genotype with the highest frequency was genotype AB (71.8%), followed by AA (19.4%), and BB (8.9%). The Indians exhibited the lowest genotype AA but the highest genotype BB, whereas genotype BB was absent in the aboriginal people. Despite the limitations, the genotype and haplotypes in the Malaysian population were successfully highlighted. The identification of ethnic-specific KIR genotypes and haplotypes provides the first step to utilizing KIR in identifying suitable transplant donors to further improve the transplant outcome in the Malaysian population.

Regulatory network of BLIMP1, IRF4, and XBP1 triad in plasmacytic differentiation and multiple myeloma pathogenesis.

Antibody secreting plasma cell plays an indispensable role in humoral immunity. As activated B cell undergoes germinal center reaction and develops into plasma cell, it gradually loses B cell characteristics and embraces functional changes associated with immunoglobulins production. Differentiation of B cell into plasma cell involves drastic changes in cell structure, granularity, metabolism, gene expression and epigenetic regulation that couple with the mounting capacity for synthesis of a large quantity of antigen-specific antibodies. The interplay between three hallmark transcriptional regulators IRF4, BLIMP1, and XBP1, is critical for supporting the cellular reprograming activities during B to plasma cell transition. IRF4 promotes plasma cell generation by directing immunoglobulin class switching, proliferation and survival; BLIMP1 serves as a transcriptional repressor that extinguishes B cell features; whereas XBP1 controls unfolded protein response that relieves endoplasmic reticulum stress and permits antibody release during terminal differentiation. Intriguingly, high expression of IRF4, BLIMP1, and XBP1 molecules have been reported in myeloma cells derived from multiple myeloma patients, which negatively impact treatment outcome, prognosis, and relapse frequency. Despite the introduction of immunomodulatory drugs in recent years, multiple myeloma is still an incurable disease with poor survival rate. An in-depth review of IRF4, BLIMP1, and XBP1 triad molecules in plasma cell generation and multiple myeloma tumorigenesis may provide clues to the possibility of targeting these molecules in disease management.

The willingness of parents to vaccinate their children younger than 12 years against COVID-19: a cross-sectional study in Malaysia.

BACKGROUND: The initiation of a new drug, for instance, the coronavirus disease 2019 (COVID-19) vaccine in children could be a source of major concern for parents. This study aims to determine the willingness of parents in Malaysia to vaccinate their children younger than 12 years against COVID-19. METHODS: An online cross-sectional survey was conducted nationwide in Malaysia from August 29, 2021, to October 17, 2021. Parents with children younger than 12 years were enrolled via the snowball sampling method. RESULTS: The analysis included data from 3,528 parents (79.5%) of the 4,438 survey responses received. Of these parents, 2,598 (73.6%) were willing, 486 (13.8%) were not willing, and 444 (12.6%) were still hesitant to vaccinate their children against COVID-19. Single parents (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.32-3.04; P = 0.001), parents with secondary or lower education (OR, 1.5; 95% CI, 1.21-1.96; P < 0.001), healthcare workers (OR, 1.7; 95% CI, 1.34-2.26; P < 0.001), parents who had significant contact with COVID-19 (OR, 1.3; 95% CI, 1.09-1.63; P = 0.006), and parents who had been vaccinated against COVID-19 (OR, 15.4; 95% CI, 9.76-24.33; P < 0.001) were found more willing to immunize their children. The common reasons for vaccination given by parents who were willing to immunize their children include protection of children (99.4%), protection of other family members (99.3%), and effectiveness (98.2%). The common reasons against vaccination given by parents who were not willing to immunize their children were uncertainty about the new vaccine (96.1%), concerns about vaccine contents (93.2%), limited vaccine information from physicians (82.3%), and the belief of vaccine was unsafe (79.8%). CONCLUSIONS: In this study, nearly three-quarters of parents were willing to vaccinate their children younger than 12 years against COVID-19. The parents' history of COVID-19 vaccination was the strongest independent predictor of their willingness to vaccinate their children. Therefore, future health education for the COVID-19 vaccine should focus on parents who are prone to vaccine refusal or hesitation, address the common reasons for vaccine refusal, and highlight the vaccine's benefits.

The effect of a single session of 30-min mindful breathing in reducing fatigue among patients with haematological cancer - a randomised controlled trial.

BACKGROUND: Patients with haematological cancer had considerable symptom burden, in which fatigue was the most prevalent. Almost 70% of haematological cancer patients reported fatigue. METHODS: We conducted a parallel-group, non-blinded, randomised control trial at the haemato-oncology unit of University Malaya Medical Centre, from 1st October 2019 to 31st May 2020. Patients included were ≥ 18 years, had histopathological diagnosis of haematological cancer, and fatigue score of ≥4 based on the fatigue subscale of Edmonton Symptom Assessment System (ESAS). Patients allocated to the intervention group received standard care plus a guided 30-min mindful breathing session, while those in control group received standard care. The study outcomes include fatigue severity according to the fatigue subscale of ESAS, visual analogue scale of 0 - 10, and Functional Assessment of Chronic Illness Therapy Fatigue Scale Version 4, at minute 0 and minute 30. RESULTS: Of 197 patients screened, 80 were eligible and they were equally randomised into 30-min mindful breathing versus standard care. Lymphoma (58.9%) was the commonest haematological malignancy, followed by multiple myeloma (13.8%), acute leukaemia (11.3%), myeloproliferative neoplasm (6.3%), chronic leukaemia (5.0%) and myelodysplastic syndrome (5.0%). There was no difference in the demographic and clinical characteristics between the 2 groups. At minute 0, both arms of patients had similar ESAS-fatigue score (median, 5) and FACIT-fatigue score (mean ± SD, 24.7 ± 10.6 for intervention group versus 24.7 ± 9.7 for control group). At minute 30, intervention group had lower ESAS-fatigue score (median, 3 versus 5) and FACIT-fatigue score (mean ± SD, 17.1 ± 10.5 versus 24.8 ± 11.3) compared to control group. Both the ESAS-fatigue score reduction (median, - 2 versus 0, p = 0.002) and FACIT-fatigue score reduction (mean ± SD, - 6.7 versus + 0.8; p < 0.001) for the intervention group were statistically significant. The calculated effect size Cohen's d was 1.4 for between-group comparison of differences in total FACIT-fatigue score. CONCLUSIONS: Our results provide evidence that a single session of 30-min mindful breathing was effective in reducing fatigue in haematological cancer patients. On top of all the currently available methods, 30-min mindful breathing can prove a valuable addition. TRIAL REGISTRATION: NCT05029024 , date of registration 15th August 2021. (Retrospectively registered).

Outcomes of high dose therapy and autologous haematopoietic stem cell transplantation for non-hodgkin lymphoma: A retrospective analysis in a resource-limited country.

AIM: To retrospectively report the clinical outcomes of non-Hodgkin's Lymphoma (NHL) patients post high dose therapy (HDT) with autologous haematopoietic stem cell transplant (AHSCT) and determine whether upfront transplant, which is a first-line consolidative treatment with induction chemotherapy, would be a feasible modality in a resource-limited country. METHODS: The medical records for NHL patients who had undergone HDT followed by AHSCT from October 1997 to November 2016 from two hospitals in Klang Valley, Malaysia were obtained from the medical record database and analysed retrospectively through statistical analysis. RESULTS: A total of 148 patients were retrospectively identified post-AHSCT, where the majority of whom had B cell lymphoma (53.4%). Majority of patients (88.5%) were in complete remission before AHSCT. The overall survival (OS) and event-free survival (EFS) at 3 years were 68.9% and 60.8%, respectively. The major cause of death was disease progression at 73.9%, while transplant-related mortality was 15.2%, with a median follow-up period of 179.5 weeks. CONCLUSION: Our study illustrates the promising outcomes of HDT with AHSCT in NHL patients in a resource-limited country. We recommend larger studies to be conducted in the future with a longer duration of follow-up to validate our findings.

Evolution of Hematopoietic Stem Cell Transplant Programs in Malaysia.

Hematopoietic stem cell transplantation (HSCT) is now widely practiced worldwide. It has the potential to cure many hematological diseases, such as acute leukemia and thalassemia. As an emerging country, Malaysia has made advancements despite many challenges. HSCT has evolved rapidly since the first pediatric allogeneic HSCT case in 1987. The first adult HSCT was performed 5 years later in 1993. Currently, a total of 13 hospitals offer HSCT services throughout Malaysia. These include private healthcare services, substantially funded government hospitals governed by the Ministry of Health, and partially funded teaching hospitals governed by the Ministry of Education. Until 2015, 1,987 allogeneic and 1,648 autologous HSCT procedures were performed. This article narrates the history and development of HSCT in Malaysia and briefly discusses the challenging issues in this area.