Immune reconstitution in children after haploidentical haematopoietic stem cell transplantation.

INTRODUCTION: Immune reconstitution (IR) kinetics of paediatric patients underwent haploidentical haematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCy) have not been extensively studied. We compared IR patterns of children receiving HSCT from haploidentical (n = 92) and HLA-matched donors (n = 36), and analysed risk factors for viral infection in these patients. METHODS: We prospectively measured lymphocyte subset numbers before HSCT and at 1, 3, 6 and 12 months after HSCT. Blood cytomegalovirus (CMV), Epstein-Barr virus, adenovirus, BK virus (BKV) and urine adenovirus and BKV viral loads were measured at designated time points. RESULTS: The median numbers of total T and T helper cells at 1 month were significantly lower in the haploidentical group compared with the HLA-matched group. Haploidentical HSCT recipients had significantly lower median numbers of several T cell subsets and B cells for 1 year after HSCT. The median NK cell count of the haploidentical group was lower at 1 month. BKV haemorrhagic cystitis, blood CMV and urine adenovirus reactivation were more frequently found in the haploidentical group. Post-haploidentical HSCT patients receiving anti-T lymphocyte globulin (ATG) had significantly lower median numbers of total T cells (at 1 month) and T helper cells (at 6 and 12 months) and higher rate of blood BKV reactivation compared with those without ATG. CONCLUSION: Paediatric patients who undergo haploidentical HSCT with PTCy are likely to have delayed IR and an increased risk of viral reactivation/infection compared with HLA-matched HSCT. The addition of ATG to PTCy delayed T cell recovery and increased risk of BKV reactivation.

Clinical Study of Long-Term Survival in Colorectal Cancer Patients in Thailand: A 10-Year Follow-Up.

Background: In Thailand, data on colorectal cancer (CRC) patient characteristics and overall survival (OS) rates are limited. We aimed to describe the overall 5-year, 10-year survival and to examine factors effecting the survival outcome among patients who were diagnoses of colorectal cancer. Methods: We reviewed medical records of patients diagnosed with invasive CRC from 2007 through 2016. Demographic and clinical data were collected upon diagnosis. Kaplan-Meier method and Cox proportional hazards model to evaluate the association of overall (OS) with risk factors. Results: A total of 3,402 CRC patients (colon 59.4%, rectum 34. 5%, and rectosigmoid 6.1%) were identified. Mean (SD) and median age were 62.9 (12.7) and 63 years old (rang 14-98 years). Stages at diagnosis were I (10.1%), II (23.3), III (35.9%) and IV (30.7%). Five-year and 10-year OS of the entire cohort were 52.7% and 41.5%, respectively. Over the part 10 years, there was a trend toward improved 5-year OS in stages I, II and III. However, 3-year OS in stage IV patients remained unchanged. Confirmed poor prognostic factors included patient age ≥65 years, high grade, and advanced stage at diagnosis. Conclusion: Advanced disease was a significant prognostic factor for shorter survival. A trend toward improvement in 5-year OS in early stages over the past decade might be related to better surgical quality, improved radiation technique, and adjuvant chemotherapy. Given that patients received better systemic treatment in stage IV disease, the reason their OS was not improved should be examined.

Estimation of sodium consumption by novel formulas derived from random spot and 12-hour urine collection.

The gold standard for estimating sodium intake is 24h urine sodium excretion. Several equations have been used to estimate 24h urine sodium excretion, however, a validated formula for calculating 24h urine sodium excretion from 12h urine collection has not yet been established. This study aims to develop novel equations for estimating 24h urine sodium excretion from 12h and random spot urine collection and also to validate existing spot urine equations in the Thai population. A cross-sectional survey was carried out among 209 adult hospital personnel. Participants were asked to perform a 12h daytime, 12h nighttime, and a random spot urine collection over a period of 24 hours. The mean 24h urine sodium excretion was 4,055±1,712 mg/day. Estimated urine sodium excretion from 3 different equations using random spot urine collection showed moderate correlation and agreement with actual 24h urine sodium excretion (r = 0.54, P<0.001, ICC = 0.53 for Kawasaki; r = 0.57, P<0.001, ICC = 0.44 for Tanaka; r = 0.60, P<0.001, ICC = 0.45 for INTERSALT). Novel equations for predicting 24h urine sodium excretion were then developed using variables derived from 12h daytime urine collection, 12h nighttime urine collection, random spot urine collection, 12h daytime with random spot urine collection, and 12h nighttime with random spot urine collection which showed strong correlation and agreement with actual measured values (r = 0.88, P<0.001, ICC = 0.87; r = 0.83, P<0.001, ICC = 0.81; r = 0.67, P<0.001, ICC = 0.62; r = 0.90, P<0.001, ICC = 0.90; and r = 0.83, p<0.001, ICC = 0.82 respectively). Bland-Altman plots indicated good agreement between predicted values and actual 24h urine sodium excretion using the new equations. Newly derived equations from 12h daytime and 12h nighttime urine collection with or without casual spot urine collection were able to accurately predict 24h urine sodium excretion.

Home-based chemotherapy for stage III colon cancer patients in Thailand: Cost-utility and budget impact analyses.

Home-based chemotherapy (HC) is a new treatment alternative to hospital-based chemotherapy treatment (IP) and is administered via portable intravenous pumps at the patient's home. HC reduces the demand for inpatient bed capacity in hospitals and reduces the cost of an infusion. This study takes a societal perspective while conducting the cost-utility and budget impact analyses (BIA) of HC and IP with an mFOLFOX6 regimen on patients with stage III colon cancer. We conducted a cost-utility analysis with a 6-month time horizon. The parameter inputs for the model were gathered from a retrospective cohort study on patients diagnosed with stage III colon cancer at Ramathibodi Hospital, Bangkok. The resource usage of HC and IP was determined based on medical records. The per-unit direct medical, home health service, and adverse events (AE) management costs were gathered from the standard cost list. The health outcome of treatment was measured in terms of quality-adjusted life years. Disutility related to AE was calculated. We conducted a sensitivity analysis for the uncertainty results and performed BIA based on the societal perspective on a 1-year time horizon. HC provided a cost-saving of $1,513.37 per patient for the period of treatment. Thus, assuming 526 patients per year, the use of HC could achieve a cumulative annual cost-saving of $828,436. HC is a cost-saving strategy compared to IP for stage III colon cancer treatment. We recommend that the service reimbursement should include national standardization in chemotherapy regimens as well as practice guidelines and protocols to prevent serious AEs.

A prognostic study of patients with cervical cancer and HIV/AIDS in Bangkok, Thailand.

Cervical cancer is one of the most common cancers of women. In Thailand, the incidence and death rate of cervical cancer are 18.1 and 5.7 per 100,000 women, respectively. Disease progresses faster in patients infected with human immunodeficiency virus (HIV) with acquired immune deficiency syndrome (AIDS). However, limited data are available for Thailand. Here we determined the prevalence of HIV/AIDS and identified factors affecting survival. We reviewed medical records of women infected with HIV with cervical cancer treated at Ramathibodi Hospital from 2007 through 2014. Demographic and clinical data were collected upon diagnosis. We used the Kaplan-Meier method and a Cox proportional hazards model to evaluate the association of overall survival (OS) with risk factors. The mean, median and range of ages at diagnosis of the 1,362 subjects were 53.9 years, 53.0 years and 20-94 years, respectively. The prevalence of HIV/AIDS in patients with cervical cancer was 2.3% and 5-year survival was 61.2%. Multivariable analysis revealed that favourable prognostic factors were a civil servant medical benefit plan and higher education. Advanced cervical cancer was a poor prognostic factor. Prognosis of women with stage III and IV cervical cancer was extremely poor (HR = 7.25 (95%CI: 4.39-11.98)) in stage III and HR = 20.57 (95%CI: 11.59-36.53) in stage IV). The 1-, 3-, and 5-year survival rates of patients with (74.2%, 67.6%, and 63.6%, respectively) or without (87.4%, 71.3% and 63.7%, respectively) HIV/AIDS were not significantly different.

Pediatric primary central nervous system tumors registry in Thailand under National Health Security Office schemes.

BACKGROUND: Few epidemiological studies of pediatric central nervous system (CNS) tumors have been performed using data from Southeast Asian national registries. Therefore, we aimed to examine data on CNS tumors from the first national childhood CNS tumor registry in Thailand. METHODS: Newly diagnosed children with benign and malignant primary CNS tumors from 20 nationwide hospitals were included. Two eras in the Thai registry were studied to compare national protocol effectiveness, including 2003-2005 (before establishment of a pediatric CNS tumor protocol) and 2011-2012 (post-establishment). RESULTS: The first study period had 300 patients with an incidence of 7.5/1,000,000 person-years and the second had 168 patients with an incidence of 13.24/1,000,000 person-years. The three most common tumors were gliomas, medulloblastoma/primitive neuroectodermal tumor (PNET), and germ cell tumors. The most common tumor site was the cerebellum, followed by the brainstem and pineal region. Five- and 10-year overall survival (OS) rates were 46.62% (95% confidence interval [CI] 40.85-52.18) and 41.78% (95% CI 36.11-47.34), respectively, for the first period. The second period had a 5-year OS of 64.75% (95% CI 56.70-71.68). OS rates for gliomas, germ cell tumors, medulloblastoma/PNET, and ependymomas were better in the second period than in the first period. CONCLUSIONS: The incidence of primary childhood CNS tumors in our study is lower compared with other reports. Improvement of OS in the second study period might be because of establishment of the Thai Pediatric Oncology Group, and national protocols for childhood CNS tumors.

Carboplatin-based regimen in pediatric intracranial germ-cell tumors (IC-GCTs): effectiveness and ototoxicity.

BACKGROUND: Induction chemotherapy with carboplatin followed by radiotherapy has been used for many years for treating intracranial germ-cell tumors (IC-GCTs) in Thailand. The objective of this study was to assess treatment outcomes, focusing on survival and ototoxicity. METHODS: The outcomes of all patients with IC-GCT treated at Ramathibodi Hospital and the Prasat Neurological Institute between 2000 and 2017 were reviewed and analyzed, including all patient characteristics and treatment modalities. Five-year overall survival (OS) and event-free survival (EFS) were analyzed using the Kaplan-Meier method, and factors affecting survival were compared using the log-rank test. RESULTS: Fifty-three patients age 1-14 years (median, 11 years) were included in this study. The median follow-up time was 63 months. The 5-year EFS and OS rates were 94.3% and 96.2% for all patients, respectively. No statistical difference in OS or EFS was observed between the data of recipients in the carboplatin-based and historical cisplatin-based therapies in our institutes. Concerning radiotherapy, omission of radiotherapy or focal irradiation results in worse long-term survival outcomes, but reduction in dose of radiotherapy to less than 40 Gy did not cause any negative impact on survival rates. Furthermore, carboplatin was associated with lower rates of hearing loss than cisplatin (5.7% vs 87.5%). CONCLUSIONS: Induction chemotherapy with carboplatin-based regimens was associated with excellent survival rates and low ototoxicity in patients with IC-GCT. Radiotherapy should be given to all patients with a minimal volume equivalent to whole-ventricular radiotherapy, during which doses of lower than 40 Gy can be effectively used.

Iodine-131 metaiodobenzylguanidine (131I-mIBG) treatment in relapsed/refractory neuroblastoma.

BACKGROUND: I-meta-iodo-benzylguanidine (I-mIBG) therapy has been used in treatment of for advanced neuroblastoma for many years with promising results. There are several studies regarding predictors and outcomes of I-mIBG therapies in relapsed/refractory neuroblastoma patients. OBJECTIVE: To identify the predictors and outcomes of I-mIBG treatment in relapsed/refractory neuroblastoma. METHODS: This study was a retrospective review of 22 patients with high risk stage IV relapsed/refractory neuroblastoma who received at least one cycle of I-mIBG therapy. Patient' characteristics, hematologic toxicity, scintigraphic semi-quantitative scoring, and overall survival were recorded. Factors predicting survival were analyzed. RESULTS: Twenty-two patients (50% male) with mean age of 3.7 years (4.8 months to 8.3 years) received I-mIBG therapies at an average of 3.8 and mean dose of 136 mCi (5032 MBq) per treatment. Most common acute hematologic toxicity was thrombocytopenia. Overall 5-year survival rate was 37% (95% confidence interval: 16.3-58.0) and median survival time was 2.8 year (95% confidence interval: 1.38-6.34). Patients with rising Curie score of ≥25% upon the second therapy were major determinants of overall survival with poorer response to treatment. At least three treatments of I-mIBG were needed to identify some degrees of survival prolongation (crude hazard ratio: P-value = 0.003). Age, sex, metastatic status, and baseline Curie scoring system were good predictors associated with survival. Seven patients (32%) demonstrated objective responses. CONCLUSION: Despite multimodality therapy, high risk neuroblastoma had a propensity of treatment failure in terms of relapsed or refractory, with some objective responses after I-mIBG treatments. The declined or non-rising Curie score upon second post-treatment total body scan was an important predictor of survival and aided a decision whether or not to proceed with bone marrow transplantation.

Impact of Serum Bicarbonate Levels on Muscle Mass and Kidney Function in Pre-Dialysis Chronic Kidney Disease Patients.

BACKGROUND: Treatment of metabolic acidosis to target the higher serum bicarbonate level than guideline recommendation may downregulate muscle protein degradation and improve renal function among chronic kidney disease (CKD) patients. We conducted a study to test the effects of increased serum bicarbonate level on muscle parameters, nutrition, and renal function in pre-dialysis CKD patients. METHODS: This was a randomized, controlled study. CKD stage 3-4 patients with serum HCO3- <22 mEq/L were randomized to either receive oral sodium bicarbonate with high target bicarbonate level of 25 ± 1 or standard level of 22 ± 1 mEq/L as control group using protocol-based titration of dosage adjustment. The changes of muscle mass measured by bioelectrical impedance analysis (BIA), muscle strength by hand grip dynamometer, estimated glomerular filtration rate (eGFR) using CKD-Epidemiology Collaboration equation, nutritional markers, and muscle-related biomarkers were determined. Data at baseline and after 4 months of sodium bicarbonate supplementation were compared between groups using Student t test or chi-square test as appropriate. RESULTS: Forty-two patients completed the study (n = 21 per group). The mean age and eGFR were 61.2 ± 9.8 years and 32.4 ± 14.1 mL/min respectively. Serum bicarbonate levels at baseline were 21.0 ± 2.1 mEq/L. Baseline data including sex, diabetes, serum bicarbonate level, creatinine, and blood pressure were similar. After 4 months of treatment, the average serum bicarbonate levels in both groups were 24.0 ± 1.4 and 20.7 ± 2.3 mEq/L (p < 0.001). Both BIA-derived total-body muscle mass and appendicular lean balance were increased at 4 months in the higher bicarbonate group (26.0 ± 5.3 to 26.7 ± 5.5 kg, p = 0.04 and 19.8 ± 4.1 to 20.7 ± 4.4 kg, p = 0.06, respectively) despite comparable body weight and protein intake. Patients in the high bicarbonate group had a significant reduction of plasma myostatin levels, a surrogate of muscle degradation, at the study exit after adjusting for baseline values (-3,137.8; 95% CI -6,235.3 to -40.4 pg/mL, p= 0.04), but unaltered insulin-like growth factor-1 level, as the mediator of muscle cell growth, (141 [106-156] to 110 [87-144] ng/mL, p = 0.13) compared to the control group. Muscle strength, eGFR as well as serum prealbumin were not significantly different between 2 groups (p > 0.05). Neither worsening hypertension nor congestive heart failure was found throughout the study. CONCLUSION: Bicarbonate supplementation to achieve the serum level ∼24 mEq/L demonstrates better muscle mass preservation in patients with pre-dialysis CKD. The impact of alkaline therapy on renal function may require a longer period of study.

The magnitude of obesity and metabolic syndrome among diabetic chronic kidney disease population: A nationwide study.

BACKGROUND: Although the prevalence of obesity and metabolic syndrome (MetS) among dialysis patients has been exceeding than general population, little is known regarding obesity and MetS in non-dialysis chronic kidney disease (CKD). We aimed to find the magnitude of obesity and MetS and their associations with impaired renal function among type 2 diabetes mellitus (T2DM) patients. METHODS: A national survey of T2DM patients was collected in the Thai National Health Security Office database during 2014-5. The sampling frame was designated as distinct geographic regions throughout the country. A stratified two-stage cluster sampling was used to select the study population. Anthropometry and 12-hour fasting blood samples were obtained by trained personnel. BMI of ≥25 kg/m2 was classified as obesity. MetS was defined as having elevated waist circumference (>90 and >80 cm in men and women, respectively) plus any two of the followings: triglyceride ≥150 mg/dL, HDL-C <40 in men or <50 mg/dL in women, blood pressure ≥130/85 mmHg, and fasting blood sugar ≥100 mg/dL. CKD was defined as an impaired renal function (eGFR <60 mL/min/1.73m2 according to the CKD-EPI equation). Logistic regression analysis was performed to examine the relationship between obesity and MetS with the presence of CKD. RESULTS: A total of 32,616 diabetic patients were finally recruited from 997 hospitals. The mean age was 61.5±10.9 years with 67.5% women. Of the participants, 35.4% were CKD patients. The prevalence of obesity was 46.5% in CKD and 54.1% in non-CKD patients with T2DM (p<0.001). In contrast, the prevalence of MetS in CKD patients was higher than their non-CKD counterparts (71.3 vs 68.8%, p<0.001). Moreover, there was an association between the prevalence of MetS with CKD stage from 3a to 5 (70.1, 72.3, 73.4, and 72.7%, respectively, p trend = 0.02). MetS, but not obesity, had a significant association with CKD in T2DM patients after adjusting for age, sex, and comorbidities [OR 1.14; 95% CI 1.06-1.22, p<0.001]. When stratified by each component of MetS, only high serum triglyceride and low HDL-C levels were increased in patients with CKD stage 4 and 5 compared with CKD stage 3 (p<0.001) and had a significant relationship with impaired renal function. CONCLUSION: There were relatively high prevalences of both obesity and MetS in T2DM patients. A higher prevalence of MetS, but lower prevalence of obesity, was observed among diabetic CKD group compared with their non-CKD counterparts. MetS, as a surrogate of insulin resistance, appeared to be more important than obesity in the development of impaired renal function in diabetic population.

Survival Analysis and Associated Factors in Thai Patients on Peritoneal Dialysis Under the PD-First Policy.

BACKGROUND: The peritoneal dialysis First (PD-First) policy means that PD is the first modality of dialysis chosen for patients with end-stage renal disease (ESRD), as put forth by the Universal Health Coverage (UHC) scheme. It was initiated in Thailand in 2008. Our aim is to analyze patient survival, technique survival, and associated factors. METHODS: Data of PD patients from January 2008 to November 2016 were studied. We calculated patient and technique survival rates (censored for death and kidney transplantation). Factors associated with survival were analyzed by the Cox proportional hazard model. Patient and technique survival rates between 2008 - 2012 and 2013 - 2016 were compared. RESULTS: Our study included 11,477 patients. The mean (standard deviation [SD]) age at initiation of PD was 54.0 (14.4) years. The level of education in 85.2% of cases was illiterate or primary school. A total of 60.9% of patients developed ESRD secondary to diabetes. The 1- to 5-year patient survival rates were 82.6, 71.8, 64.0, 58.5, and 54.0%, respectively. The first-year technique survival rate was 94.8%. The patient and technique survival rates during 2013 - 2016 were better than those seen during 2008 - 2012. Factors associated with lower patient survival rates were: female gender, increased age at start of PD, coverage with civil servant medical benefit scheme, low educational levels, and a history of diabetes. CONCLUSION: Most patients had diabetes and low educational levels as seen in the outcomes in the previous literature. These factors impacted the survival of patients under the PD-First policy.