Marrow Fat-Cortical Bone Relationship in ß-Thalassemia: A Study Using MRI.

BACKGROUND: Growing evidence suggests that marrow adipocytes play an active role in the regulation of bone metabolism and hematopoiesis. However, research on the relationship between bone and fat in the context of hematological diseases, particularly ß-thalassemia, remains limited. PURPOSE: To investigate the relationship between marrow fat and cortical bone thickness in ß-thalassemia and to identify key determinants influencing these variables. STUDY TYPE: Prospective. SUBJECTS: Thirty-five subjects in four subject groups of increasing disease severity: 6 healthy control (25.0 ± 5.3 years, 2 male), 4 ß-thalassemia minor, 13 intermedia, and 12 major (29.1 ± 6.4 years, 15 male). FIELD STRENGTH/SEQUENCE: 3.0 T, 3D fast low angle shot sequence and T1-weighted turbo spin echo. ASSESSMENT: Analyses on proton density fat fraction (PDFF) and R2* values in femur subregions (femoral head, greater trochanter, intertrochanteric, diaphysis, distal) and cortical thickness (CBI) of the subjects' left femur. Clinical data such as age, sex, body mass index (BMI), and disease severity were also included. STATISTICAL TESTS: One-way analysis of variance (ANOVA), mixed ANOVA, Pearson correlation and multiple regression. P-values <0.05 were considered significant. RESULTS: Bone marrow PDFF significantly varied between the femur subregions, F(2.89,89.63) = 44.185 and disease severity, F(1,3) = 12.357. A significant interaction between subject groups and femur subregions on bone marrow PDFF was observed, F(8.67,89.63) = 3.723. Notably, a moderate positive correlation was observed between PDFF and CBI (r = 0.33-0.45). Multiple regression models for both PDFF (R2 = 0.476, F(13,151) = 10.547) and CBI (R2 = 0.477, F(13,151) = 10.580) were significant. Significant predictors for PDFF were disease severity (ßTMi = 0.36, ßTMa = 0.17), CBI (ß = 0.24), R2* (ß = -0.32), and height (ß = -0.29) while for CBI, the significant determinants were sex (ß = -0.27), BMI (ß = 0.55), disease severity (ßTMi = 2.15), and PDFF (ß = 0.25). DATA CONCLUSION: This study revealed a positive correlation between bone marrow fat fraction and cortical bone thickness in ß-thalassemia with varying disease severity, potentially indicating a complex interplay between bone health and marrow composition. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

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.

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.

Bone Marrow Fat Distribution in Patients With ß-Thalassemia: A Study Using Chemical Shift-Based Water-Fat MRI.

RATIONALE AND OBJECTIVES: Molecular studies have shown the changes in bone marrow fat in relation to altered hematopoiesis. This study aims to investigate the changes in the bone marrow fat in patients affected by ß-thalassemia by using chemical shift-encoded (CSE)-MRI. MATERIALS AND METHODS: Twenty-three subjects, comprising of six healthy (17-31 years old) and 17 ß-thalassemia subjects (19-39 years old), were scanned using a multiecho fast low angle shot sequence (0.94 × 0.94 × 3.00 mm3) and a stimulated echo acquisition mode sequence using 3T MRI. Bone marrow proton density fat fraction (PDFF) was quantified in the left femur of each subject. Regression and Bland-Altman analysis were used to analyze agreement between CSE-MRI and 1H-MRS. PDFF distribution was analyzed using Hartigan's dip test and the computed Wasserstein distances. Jonckheere-Terpstra trend analysis was performed to evaluate the effect of disease severity on PDFF distribution. RESULTS: An excellent agreement was found between PDFF measured using CSE-MRI with 1H-MRS (R2 = 0.91; bias =-1.41%). Healthy subjects showed left-skewed or bimodal PDFF distribution while ß-thalassemia subjects showed bimodal, normal or right-skewed distribution. Jonckheere-Terpstra test shows that PDFF distribution was increasingly different from the norm as disease severity increased (TJT = 166.0, z = 3.806, p < 0.05). Increase in variability of PDFF distribution within each subject group was also seen with increasing disease severity (TJT = 169.0, z = 3.971, p < 0.05). CONCLUSION: CSE-MRI is a promising tool to demonstrate spatial changes and variability in marrow fat distribution, resulting from ineffective erythropoiesis.

Marrow Fat Content and Composition in ß-Thalassemia: A Study using 1 H-MRS.

BACKGROUND: ß-thalassemia is a genetic disease that causes abnormal production of red blood cells (ineffective erythropoiesis, IE). IE is a condition known to change bone marrow composition. PURPOSE: To evaluate the effect of IE on the marrow fat content and fat unsaturation levels in the proximal femur using 1 H-MRS. STUDY TYPE: Prospective. SUBJECTS: Twenty-three subjects were included in this study, seven control and 16 ß-thalassemia subjects. FIELD STRENGTH/SEQUENCE: 3.0T; stimulated echo acquisition Mode (STEAM); magnetic resonance spectroscopy (MRS) sequence. ASSESSMENT: Multiecho MRS scans were performed in four regions of the proximal left femur of each subject, that is, diaphysis, femoral neck, femoral head, and greater trochanter. The examined regions were grouped into red (diaphysis and femoral neck) and yellow marrow regions (femoral head and greater trochanter). STATISTICAL TESTS: The Jonckheere-Terpstra test was used to evaluate the impact of increasing disease severity on bone marrow fat fraction (BMFF), marrow conversion index, and fat unsaturation index (UI). Pairwise comparison analysis was performed when a significant trend (P < 0.05) was found. K-means clustering analysis was used to examine the clusters observed when BMFF in the red and yellow regions were studied (diaphysis against greater trochanter). RESULTS: BMFF showed a significant decreasing trend with increasing disease severity in both red (TJT = 109.00, z = -4.414, P < 0.05) and yellow marrow regions (TJT = 108.00, z = -4.438, P < 0.05). The opposite trend was observed in UI in both bone marrow regions (red marrow: TJT = 180.5, z = 3.515, P < 0.05; yellow marrow: TJT = 155.0, z = 2.282, P = 0.05). Three distinct forms of marrow adipogenesis were found when plotting BMFF diaphysis against BMFF greater trochanter: 1) normal (centroid: 80.4%, 66.6%), 2) partial disruption (centroid: 51.1%, 16.6%), and 3) total disruption (centroid: 2.6%, 1.6%). DATA CONCLUSION: ß-thalassemia is associated with decreased marrow fat, and increased marrow fat unsaturation level. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Translation, adaptation and validation of two versions of the Chronic Liver Disease Questionnaire in Malaysian patients for speakers of both English and Malay languages: a cross-sectional study.

OBJECTIVE: We aimed to adapt, translate and validate the Chronic Liver Disease Questionnaire (CLDQ) in Malaysian patients with chronic liver diseases of various aetiologies. SETTING: Tertiary level teaching institution in Malaysia. PARTICIPANTS: The validation process involved 211 adult patients (English language n=101, Malay language n=110) with chronic liver disease. Characteristics of the study subjects were as follows: mean (SD) age was 56 (12.8) years, 58.3% were male and 41.7% female. The inclusion criteria were patients 18 years or older with chronic hepatitis and/or liver cirrhosis of any aetiology. The exclusion criteria were as follows: presence of hepatic encephalopathy, ongoing treatment with interferon and presence of other chronic conditions that have an impact on health-related quality of life (HRQOL). METHODS: A cross-sectional study was conducted. Cultural adaptation of the English version of the CLDQ was performed, and a Malay version was developed following standard forward-backward translation by independent native speakers. Psychometric properties of both versions were determined by assessing their internal consistency, test-retest reliability and discriminant and convergent validity. RESULTS: Cronbach's alpha for internal consistency across the various domains of the CLDQ was 0.95 for the English version and 0.92 for the Malay version. Test-retest analysis showed excellent reliability with an intraclass correlation coefficient of 0.89 for the English version and 0.93 for the Malay version. The average scores of both the English and Malay versions of the CLDQ demonstrated adequate discriminant validity by differentiating between non-cirrhosis (English 6.3, Malay 6.1), compensated cirrhosis (English 5.6, Malay 6.0) and decompensated cirrhosis (English 5.1, Malay 4.9) (p<0.001). Convergent validity showed that correlation was fair between the English (ρ=0.59) and Malay (p=0.47) CLDQ versions with the EQ-5D, a generic HRQOL instrument. CONCLUSION: The English and Malay versions of the CLDQ are reliable and valid disease-specific instruments for assessing HRQOL in Malaysian patients with chronic liver disease.