A review on the epidemiology of invasive fungal infections in Asian patients with haematological malignancies (2011-2021).

The incidences of invasive fungal infection (IFI) are increasing especially in patients diagnosed with haematological malignancies due to their immunocompromised nature. Risk factors include advanced age, exposure to immunosuppressants, neutropenia and catheter usage. Some of the most common organisms reported are Candida and Aspergillus species while other fungal species including Scedosporium, Ttrichosporon, Cryptococcus and Fusarium have also increasingly been reported in the past years. However, the epidemiological data on IFI amongst patients with haematological malignancies in Asian countries are lacking and therefore, we aim to investigate published epidemiological data on such cases in the last 10 years (2011-2021) and to discuss the challenges faced in the diagnosis and management of IFI.

Discovery of lung adenocarcinoma tumor antigens and ferroptosis subtypes for developing mRNA vaccines.

mRNA vaccines are becoming a feasible alternative for treating cancer. To develop mRNA vaccines against LUAD, potential antigens were identified and LUAD ferroptosis subtypes distinguished for selecting appropriate patients. The genome expression omnibus, cancer genome atlas (TCGA) and FerrDB were used to collect gene expression profiles, clinical information, and the genes involved in ferroptosis, respectively. cBioPortal was used to visualize and compare genetic alterations, GEPIA2 to calculate prognostic factors of the selected antigens, and TIMER to visualize the relationship between potential antigens and tumor immune cell infiltration. Consensus clustering analysis was utilized to identify ferroptosis subtypes and their prognostic value assessed by Log-rank and cox regression tests. The modules of ferroptosis-related gene screening were conducted by weight gene co-expression network analysis. The LUAD ferroptosis landscape was visualized through dimensionality reduction and graph learning. Six tumor antigens had obvious LUAD-mutations, positively correlated with different antigen-presenting cells, and might induce tumor cell ferroptosis. LUAD patients were stratified into three ferroptosis subtypes (FS1, FS2, and FS3) according to diverse molecular, cellular, and clinical characteristics. FS3 showed the highest tumor mutation burden and the most somatic mutations, deemed potential indicators of mRNA vaccine effectiveness. Moreover, different ferroptosis subtypes expressed distinct immune checkpoints and immunogenic cell death modulators. AGPS, NRAS, MTDH, PANX1, NOX4, and PPARD are potentially suitable for mRNA vaccinations against LUAD, specifically in patients with FS3 tumors. This study defines vaccination candidates and establishes a theoretical basis for LUAD mRNA vaccinations.

Down-regulation of miR-21-5p by pirfenidone to inhibit fibroblast proliferation in the treatment of acquired tracheal stenosis.

OBJECTIVE: Treatment options for acquired tracheal stenosis (ATS) are limited due to a series of pathophysiological changes including inflammation and cell proliferation. Micro ribonucleic acid-21-5p (miR-21-5p) may promote the excessive proliferation of fibroblasts. However, various types of fibrosis can be prevented with pirfenidone (PFD). Currently, the effect of PFD on miR-21-5p and its biological function has not been clarified. In this study, PFD was evaluated as a potential treatment for ATS by inducing fibroblast proliferation in lipopolysaccharide (LPS)-induced fibroblasts by targeting miR-21-5p. METHODS: For 48 h, 1 g/ml LPS was used to generate fibroblasts in vitro, followed by the separation of cells into four groups: control, PFD, mimic, and mimic + PFD. The Cell Counting Kit-8 (CCK-8) technique was adopted to measure the proliferation of fibroblasts. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) were used to measure the relative expressions of tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), drosophila mothers against decapentaplegic 7 (Smad7) and collagen type I alpha 1(COL1A1) messenger RNA (mRNA) and proteins, respectively. RESULTS: (1) At 0, 24, 48, and 72 h, fibroblast growth was assessed using the CCK-8 method. Compared with the control group, the mimic group showed the highest fibroblast viability, and the PFD group showed the lowest fibroblast viability. However, fibroblast viability increased in the mimic + PFD group but decreased in the mimic one. (2) RT-qPCR and WB showed that the mimic group exhibited a significant up-regulation in the relative expressions of TNF-α, TGF-ß1, and COL1A1 mRNA and proteins but a down-regulation in the relative expression of Smad7 mRNA and protein compared with the control one. In the PFD group, the results were the opposite. Nevertheless, the relative expressions of TNF-α, TGF-ß1, and COL1A1 mRNA and proteins were increased, whereas that of Smad7 mRNA was decreased in the mimic + PFD group. The change was less in the mimic group. CONCLUSION: PFD may have a preventive and curative effect on ATS by inhibiting fibroblast proliferation and the fibrotic process and possibly through down-regulating miR-21-5p and up-regulating Smad7 and its mediated fibrotic and inflammatory responses.

Case Series of Hepatosplenic T-Cell Lymphoma: A Rare and Aggressive Disease.

Hepatosplenic T-cell lymphoma is a rare form of T-cell lymphoma that predominantly emerges from neoplastic proliferation of cytotoxic T cells of γ/δ T-cell receptor-expressing lymphocytes. Isochromosome 7q and trisomy 8 are the most prevalent chromosomal abnormalities associated with hepatosplenic T-cell lymphoma, and most patients have mutations in genes related to chromatin remodeling or the JAK/STAT system. Hepatosplenic T-cell lymphoma can mimic various infectious diseases, immunological conditions, and other malignancies. Patients usually present with nonspecific constitutional symptoms and spleen and liver enlargement, with variable degrees of cytopenia. The rarity of this disease, coupled with the lack of lymph node involvement that is usually seen in lymphomas, causes significant difficulty in diagnosis, which inevitably delays the initiation of treatment. Managing this lymphoma is arduous because of its late presentation and aggressive nature, frequently resulting in rapid progression in its clinical course and refractoriness to conventional chemotherapy. There is a lack of international guidelines for its treatment, and in most cases, treatment is guided by case series. Here, we highlight the clinicopathological features and management of hepatosplenic T-cell lymphoma over a 10-year span in a single hematology referral center and review the literature.

Analysis of clinical characteristics of 617 patients with benign airway stenosis.

Introduction: Benign airway stenosis (BAS), namely airway narrowing caused by a variety of benign lesions, can lead to varying degrees of breathing difficulties and even death due to asphyxia. This study aimed to elucidate the clinical characteristics of BAS, including etiology, treatment and pathology, by analyzing the clinical data of BAS patients. Methods: A retrospective analysis was conducted using the clinical data of 617 BAS cases from January 2017 to December 2022. The pathological characteristics of the tissues were assessed by hematoxylin-eosin (H&E) and Masson's staining. Besides, protein expression levels were determined by immunohistochemistry (IHC). Results: A total of 617 patients were included (333 females [53.97%] and 284 males [46.03%]), with an average age of 48.93 ± 18.30 (range 14-87). Tuberculosis (n = 306, 49.59%) and trauma (n = 179, 29.02%) were the two leading etiologies of BAS, followed by airway foreign bodies (FB, n = 74, 11.99%), external compression (n = 25, 4.05%) and other etiologies (n = 33, 5.35%). Among 306 tuberculous tracheobronchial stenosis (TBTS) cases, most were females (n = 215, 70.26%), and TBTS mainly occurred in the left main bronchus (n = 97, 31.70%), followed by the right middle bronchus (n = 70 cases, 22.88%). The majority of TBTS patients (n = 259, 84.64%) were treated by interventional therapy. The condition of 179 BAS patients was ascribed to trauma, such as tracheal intubation (n = 92, 51.40%), tracheotomy (n = 69, 38.56%), injury (n = 15, 8.38%) and surgery (n = 3, 1.68%), which mostly took place in the trachea (n = 173, 96.65%). TAS patients mainly received interventional therapy (n = 168, 93.85%) and stent implantation (n = 47, 26.26%). The granulation tissues of BAS primarily featured inflammation, proliferation and fibrosis. IHC indicated the up-regulated expressions of transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), collagen type I protein (COL-I) and vimentin, and the down-regulated expression of E-cadherin, which indicated fibrosis and epithelial-mesenchymal transition (EMT). Conclusion: Tuberculosis was the main etiology, and trauma was the secondary etiology. The granulation tissues of BAS were characterized by inflammation, fibrosis and probably EMT. Comprehensive interventional therapy is an effective method of treating BAS.

Distribution and chemotactic mechanism of CD4+ T cells in traumatic tracheal stenosis.

A systemic and local inflammatory immune imbalance is thought to be the cause of traumatic tracheal stenosis (TS). However, with CD4+ T lymphocytes being the predominant immune cells in TS, the mechanism of action and recruitment has not been described. In our research, using flow cytometry, ELISA, immunofluorescence, and Transwell chamber assays, the expression, distribution, and potential chemotactic function of CD4+ T cells in TS patients were examined before and after treatment. The results showed that the untreated group had significantly more CD4+ T cells and their secreted TGF-ß1 than the treated group. Additionally, the untreated group's CD4+ T cells showed a significant rise in CCL22 and CCL1, as well as a larger proportion of CCR4 and CCR8. CD4+ T cells and CD68+ macrophages located in TS also expressed CCL1 and CCL22. In vitro, anti-CCL1 and anti-CCL22 can partially block the chemoattractant effect of TS bronchoalveolar lavage (BAL) on purified CD4+ T cells. The findings of this study indicated that TS contained unbalanced CD4 immune cells that were actively recruited locally by CCR4/CCL22 and CCR8/CCL1. As a result, it is anticipated that CD4 immune rebalancing can serve as a novel treatment for TS.

Oral and Gut Microbiota Dysbiosis is Associated with Mucositis Severity in Autologous Hematopoietic Stem Cell Transplantation: Evidence from an Asian Population.

Mucositis is a debilitating complication of hematopoietic stem cell transplantation (HSCT). It is unclear how changes in the composition of microbiota, which are modulated by geographical location and ethnicity, may influence immune regulation leading to the development of mucositis, and the study of both oral and gut microbiota in a single population of autologous HSCT in the Asian region is lacking. The present study aimed to characterize the oral and gut microbiota changes, and the impact on both oral and lower gastrointestinal (GI) mucositis, with associated temporal changes in a population of adult recipients of autologous HSCT. Autologous HSCT recipients age ≥18 years were recruited from Hospital Ampang, Malaysia, between April 2019 and December 2020. Mucositis assessments were conducted daily, and blood, saliva, and fecal samples were collected prior to conditioning, on day 0, and at 7 days and 6 months post-transplantation. Longitudinal differences in alpha diversity and beta diversity were determined using the Wilcoxon signed-rank test and permutational multivariate analysis of variance, respectively. Changes in relative abundances of bacteria across time points were assessed using the microbiome multivariate analysis by linear models function. The combined longitudinal effects of clinical, inflammatory, and microbiota variables on mucositis severity were measured using the generalized estimating equation. Among the 96 patients analyzed, oral mucositis and diarrhea (representing lower GI mucositis) occurred in 58.3% and 95.8%, respectively. Alpha and beta diversities were significantly different between sample types (P < .001) and across time points, with alpha diversity reaching statistical significance at day 0 in fecal samples (P < .001) and at day +7 in saliva samples (P < .001). Diversities normalized to baseline by 6 months post-transplantation. Significant microbiota, clinical, and immunologic factors were associated with increasing mucositis grades. Increasing relative abundances of saliva Paludibacter, Leuconostoc, and Proteus were associated with higher oral mucositis grades, whereas increasing relative abundances of fecal Rothia and Parabacteroides were associated with higher GI mucositis grades. Meanwhile, increasing relative abundances of saliva Lactococcus and Acidaminococcus and fecal Bifidobacterium were associated with protective effects against worsening oral and GI mucositis grades, respectively. This study provides real-world evidence and insights into the dysbiosis of the microbiota in patients exposed to conditioning regimen during HSCT. Independent of clinical and immunologic factors, we demonstrated significant associations between relative bacteria abundances with the increasing severity of oral and lower GI mucositis. Our findings offer a potential rationale to consider the inclusion of preventive and restorative measures targeting oral and lower GI dysbiosis as interventional strategies to ameliorate mucositis outcome in HSCT recipients.

Prospective longitudinal analysis of clinical and immunological risk factors associated with oral and gastrointestinal mucositis following autologous stem cell transplant in adults.

PURPOSE: The study aimed to characterize the incidence of both oral and gastrointestinal (GI) mucositis, its' associated temporal changes in local and systemic pro-inflammatory cytokines, and to explore predictive clinical and immunological factors associated with their occurrences in hematopoietic stem cell transplant (HSCT). METHODS: Autologous HSCT patients aged 18 years old and above were recruited from Hospital Ampang, Malaysia, between April 2019 to December 2020. Mucositis assessments were conducted daily, whilst blood and saliva were collected prior to conditioning regimen, on Day 0, Day+7 and 6-month. Baseline and inflammatory predictors in a repeated time measurement of moderate-severe mucositis were assessed by multiple logistic regression and generalized estimating equations, respectively. RESULTS: Of the 142 patients analyzed, oral mucositis and diarrhea (representing GI mucositis) were reported as 68.3% and 95.8%, respectively. Predictive factors for moderate-severe oral mucositis were BEAM or busulphan-based regimens (odds ratio (OR)=9.2, 95% confidence interval (CI)=1.16-72.9, p-value (p) = 0.005) and vomiting (OR=4.6, 95% CI 1.68-12.3, p = 0.004). Predictive factors for moderate-severe GI mucositis were BEAM or busulphan-based regimens (OR=3.9, 95% CI 1.05-14.5, p = 0.023), female sex (OR = 3.3, 95% CI 1.43-7.44, p = 0.004) and body mass index (OR=1.08, 95% CI 1.02-1.15, p = 0.010). Cytokines analyses were performed in 96 patients. Saliva and plasma interleukin-6 (OR=1.003, 95% CI 1.001-1.004, p < 0.001 and OR=1.01, 95% CI 1.001-1.015, p = 0.029), and plasma tumor necrosis factor-alpha (OR=0.91, 95% CI 0.85-0.99, p = 0.019) were predictive of moderate-severe oral mucositis in a time-dependent model. CONCLUSION: This study provides real-world evidence and insights into patient- and treatment-related factors affecting oral and GI mucositis in HSCT.

Psychometric evaluation of Oral Mucositis Daily Questionnaire: A cross-cultural adaptation of the Malay version in multiethnic adult autologous stem cell transplant.

Objective: Mucositis is one of the most feared side effects of cancer treatment. Psychometric analysis of a patient self-assessment score, the oral mucositis daily questionnaire in Malay (OMDQ-Mal) and its construct validity by means of confirmatory factor analysis (CFA) is lacking. This research aimed to test the validity and reliability of OMDQ-Mal. Methods: A total of 114 autologous stem-cell transplantation patients aged ≥ 18 years old at a national hematology center in Malaysia from April 2019 to December 2020 completed OMDQ-Mal concurrently with physician scores. Internal consistency and reproducibility were determined by Cronbach alpha and intraclass correlation coefficient, respectively. Correlations with physician scores were determined by Spearman correlation. Discriminative validity and construct validity were determined by Mann-Whitney U and CFA, respectively. Results: OMDQ-Mal demonstrated high internal consistency (α â€‹= â€‹0.874). Test-retest reliability between paired days were moderate to excellent (95% CI â€‹= â€‹0.676-0.953). Items in OMDQ-Mal had moderate to strong correlations with physician scores (ρ â€‹= â€‹0.503-0.721). Discriminative validity indicated that the scores of scales were significantly different between participants with severe and mild conditions. Construct validity results of loading factors 0.708-0.952; composite reliability 0.879-0.974; average variant extracted 0.710-0.841; and heterotrait-monotrait ratio 0.528 established the convergent and divergent validity. Conclusions: In conclusion, the OMDQ-Mal, which captured important quality of life responses, demonstrated adequate validity and reliability. This was supported by a two-component model CFA. The strong correlation of OMDQ-Mal with both physician scores indicated its potential as a comprehensive patient-reported outcome measure of mucositis of the entire alimentary tract.

Plasma Cell Leukemia with Successful Upfront Venetoclax in Combination with Allogeneic Transplantation.

BACKGROUND Plasma cell leukemia (PCL) is an aggressive form of plasma cell neoplasm. We report the first case of primary PCL successfully treated with upfront novel agents consisting of Venetoclax and daratumumab in combination with intensive chemotherapy and allogeneic transplantation. CASE REPORT A 59-year-old woman presented with epistaxis, gum bleeding, and blurred vision. On examination, she appeared pale, with multiple petechiae and hepatomegaly. Fundoscopy revealed retinal hemorrhages. Laboratory investigations revealed bicytopenia and leukocytosis, with mild coagulopathy and hypofibrinogenemia. Elevated globulin and calcium levels were also observed. Serum protein electrophoresis demonstrated IgG lambda paraproteinemia, with a serum-free light chain kappa-to-lambda ratio of 0.074. A skeletal survey revealed the presence of lytic lesions. Bone marrow investigations confirmed the presence of lambda-light-chain-restricted clonal plasma cells. FISH detected t(11;14) and 17p13.1 deletion. Therefore, a final diagnosis of primary PCL was made. The patient received 1 cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) and 5 cycles of Venetoclax-VCD, followed by an unsuccessful stem cell mobilization. One cycle of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (VRD) was then given. The patient achieved complete remission. She underwent allogeneic stem cell transplantation of an HLA-matched sibling donor. Post-transplant marrow assessment showed disease remission and absence of t(11;14) and 17p deletions. She was administered pamidronate and lenalidomide maintenance. She remained clinically well with a good performance status and no active graft-versus-host disease 18 months after transplant. CONCLUSIONS The success of our patient in achieving complete remission has highlighted the efficacy and safety of this novel therapy in the front-line management of PCL.

Allogeneic hematopoietic cell transplantation in patients with chronic phase chronic myeloid leukemia in the era of third generation tyrosine kinase inhibitors: A retrospective study by the chronic malignancies working party of the EBMT.

Following the introduction of tyrosine kinase inhibitors (TKI), the number of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for chronic phase (CP) chronic myeloid leukemia (CML) has dramatically decreased. Imatinib was the first TKI introduced to the clinical arena, predominantly utilized in the first line setting. In cases of insufficient response, resistance, or intolerance, CML patients can subsequently be treated with either a second or third generation TKI. Between 2006 and 2016, we analyzed the impact of the use of 1, 2, or 3 TKI prior to allo-HCT for CP CML in 904 patients. A total of 323-, 371-, and 210 patients had 1, 2, or 3 TKI prior to transplant, respectively; imatinib (n = 778), dasatinib (n = 508), nilotinib (n = 353), bosutinib (n = 12), and ponatinib (n = 44). The majority had imatinib as first TKI (n = 747, 96%). Transplants were performed in CP1, n = 549, CP2, n = 306, and CP3, n = 49. With a median follow-up of 52 months, 5-year OS for the entire population was 64.4% (95% CI 60.9-67.9%), PFS 50% (95% CI 46.3-53.7%), RI 28.7% (95% CI 25.4-32.0%), and NRM 21.3% (95% CI 18.3-24.2%). No difference in OS, PFS, RI, or NRM was evident related to the number of TKI prior to allo-HCT or to the type of TKI (p = ns). Significant factors influencing OS and PFS were > CP1 versus CP1 and Karnofsky performance (KPS) score > 80 versus ≤80, highlighting CP1 patients undergoing allo-HCT have improved survival compared to >CP1 and the importance of careful allo-HCT candidate selection.

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.

A quality assessment of online patient information regarding tonsillitis using the EQIP tool.

BACKGROUND: Tonsillitis is a common paediatric condition. The decision to seek medical attention and consent to treatment is usually made by parents or guardians. With increased accessibility of the internet, online medical information plays an increasingly significant role in the decision-making process. Little is known regarding the quality of online patient information on tonsillitis, as this has not been previously studied. OBJECTIVE: The aim of our study was to identify the quality of information regarding tonsillitis on websites intended for the public. METHODS: We conducted a systematic review of online information on tonsillitis using the following search terms: "Tonsillectomy", "Tonsillitis", "Adenotonsillectomy" and "Tonsil". The first three pages of returned websites were captured and each website was examined using the validated Ensuring Quality Information for Patients (EQIP) tool (score 0-36). RESULTS: A total of 92 websites met the inclusion criteria for analysis. The overall median EQIP score was 19 with an interquartile range of 17-22 and a maximum of 32. More than half of all websites originated from the USA (61%) and hospitals were the most common source of information (29%). Most websites failed to describe the quantitative benefits or address the medical intervention costs and insurance issues. Half of the websites included both tonsillectomy and antibiotics as treatments for tonsillitis. Only 68% included complications of tonsillitis or tonsillectomy. CONCLUSIONS: The assessment of the quality of online patient information websites regarding tonsillitis by the EQIP tool indicates that most websites were of poor credibility, with minimal information regarding treatment choices and complications. To improve awareness of tonsillitis, there is a need for more informative and patient-centred websites that are compatible with the international quality standard for patient information.

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.

Allogeneic Hematopoietic Stem Cell Transplantation in Severe Aplastic Anemia: A Single Centre Experience in Malaysia.

Background: Hematopoietic stem cell transplantation (HSCT) provides curative therapy in almost 90% of patients with severe aplastic anemia (SAA). Older age, long duration of disease with consequent heavy exposure to transfusion, and active infection at the time of HSCT have a negative influence on the outcomes, causing graft failure (GF) and graft versus host disease (GVHD). Purpose: To describe the outcomes of all patients with SAA who received hematopoietic stem cell transplantation at a tertiary center in Malaysia. Materials and methods: We included a 20 y cohort of patients who underwent transplantation from January 1, 1999 to December 31, 2019. Data were obtained from electronic medical records. Demographics, clinical characteristics, and treatment outcomes were analyzed using descriptive statistics. Overall survival (OS) was analyzed using Kaplan-Meier curves. All analyses were conducted using the Statistical Package for the Social Sciences (SPSS) version 25. Results: Eighty patients were analyzed. The median age at diagnosis was 19 years, and 59% patients were male (n = 47). Malay ethnicity was the highest (52.5%), followed by Chinese (20.0%) and Native Sabah (15.0%). The median duration from diagnosis to transplantation was 13.5 weeks. A majority of patients received Cy-ATG conditioning (n = 51, 63.8%). Forty-one patients (51.2%) used peripheral blood as stem cell source, 36 patients (45.0%) used granulocyte colony stimulating factor (G-CSF) primed marrow graft and 3 patients (3.8%) used both. The mean nucleated mononuclear cell and CD34 cell doses were 4.7 ± 1.7 × 108/kg and 4.6 ± 1.9 × 106/kg, respectively. Median engraftment for WBCs and platelets was 14 and 15 days, respectively. There was no difference in WBC and platelet engraftment in patients who received peripheral blood stem cell transplantation or bone marrow transplant. At a median follow-up of 54 months, 49 patients (61.3%) achieved complete remission and 8 patients (10.0%) achieved partial remission. The estimated 5 y OS was 63% and higher among those who received HSCT within 3 months of diagnosis. Twenty-two patients (27.5%) died within 100 d of transplantation, and a majority of these died due to pre-engraftment death. Discussion and conclusions: Our study found that patients who received early allogeneic transplantation for SAA had better outcomes. Pre-engraftment failure was the major cause of transplant-related mortality within 100 d. Further studies are required to identify the factors responsible for delaying transplantation to improve treatment outcomes.

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.

A variant e13a3 BCR-ABL1 fusion transcript in refractory adult B-cell acute lymphoblastic leukemia achieving complete remission with CAR-Tcell therapy.

Acute lymphoblastic leukemia (ALL) cases with e13a3 fusion transcripts are extremely rare. We report a 24-year-old male with Ph-positive (Ph+) ALL with an aberrant e13a3 fusion transcript treated with CD19-specific chimeric antigen receptor T-cell (CAR-T) therapy. He developed refractory disease post-chemotherapy induction, andreceived allogeneic hematopoietic stem cell transplantation (allo-HSCT) after salvage with imatinib in combination with chemotherapy regimen. Unfortunately, the patient relapsed after +90 days post-transplant. He was consented to CAR-T therapy trial and achieved complete remission, highlighting the efficacy of CAR-T treatment in relapsed-refractory B-ALL irrespective of the underlying genetic drivers in leukemia cells .

Occult Disseminated Metastatic Breast Carcinoma Presenting as Acquired Thrombotic Thrombocytopenic Purpura.

Cancer-related microangiopathic hemolytic anemia (MAHA) is a rare and life-threatening condition. We present a patient who had been treated for invasive lobular breast carcinoma in clinical remission with fever and hemolytic anemia. The peripheral blood film showed MAHA and thrombocytopenia, and a functional deficiency of ADAMTS13 activity of 23% consistent with acquired thrombotic thrombocytopenic purpura. Bone marrow aspirate and trephine biopsy confirmed metastatic carcinoma. Further evaluation revealed the involvement of multiple bone sites without recurrence of the primary tumor. The patient received a daily plasma exchange with cryosupernatant and was pulsed with corticosteroids. MAHA related to breast cancer appears to be a rare occurrence.

Autologous stem cell transplantation (ASCT) outcome for multiple myeloma in a tertiary referral centre in Malaysia.

Background: Multiple Myeloma (MM) is characterized by the presence of clonal plasma cells. These often result in complications including bone destruction, hypercalcemia, renal insufficiency, and anaemia. Induction with a triplet or quadruplet regimen followed by autologous stem cell transplantation (ASCT) has been the standard of care for transplant eligible patients to achieve durable remission. Purpose: This is a retrospective analytical study to determine the outcome of Multiple Myeloma patients who underwent ASCT in Ampang Hospital. Materials and Methods: We included a 5-year cohort of patients transplanted from 1st July 2014 to 30th June 2019. Data were obtained through electronic medical records. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed using simple and multiple Cox proportional hazard regression analysis. All analyses were done using software R version 3.6.2 with validated statistical packages. Results: 139 patients were analyzed. The median age at transplant was 56 years old and 56.1% are males (n＝78). The most common subtype is IgG Kappa (n＝67, 48.2%). Only 93 patients in which the International Staging System (ISS) could be determined, and among them, 33.3% of patients (n＝31) have advanced stage Ⅲ disease. The most common induction received before ASCT was a bortezomib based regimen and/or an immunomodulatory (IMiD) based regimen. 63.3% of patients achieved at least a very good partial response (VGPR) before ASCT. Most patients received myeloablative conditioning (MAC) (n＝119, 85.6%). The mean cell dose is 3.68×106/kg. The median time to engraftment was 11 days for both platelet and absolute neutrophil count (ANC). With the median follow-up of 17.3 (range, 6.2-33.4) months, the median OS and PFS were not reached. The 1-year and 2-year PFS were 75% (95% CI 66-82%) and 52% (95% CI 42-62%), respectively. The 1-year and 2-year OS were 82% (95% CI 74-88%) and 70% (95% CI 60-78%), respectively. 6 patients (4.3%) had transplant-related mortality (TRM). IgA subtype was found to adversely affect PFS. Maintenance therapy and the absence of renal impairment was associated with better PFS and OS. Discussion and Conclusions: Our study found that ASCT following induction treatment is safe and beneficial to achieve a deeper remission status. In our study, the addition of maintenance therapy is associated with an improved outcome in PFS and OS.