Survival outcomes of myeloid leukemia associated with Down syndrome and de novo acute myeloid leukemia in children: Experience from a single tertiary center in Thailand.

Few studies have reported the survival outcomes of myeloid leukemia associated with Down syndrome (DS) in resource-limited countries. This study aimed to compare characteristics and survival outcomes of children with acute myeloid leukemia (AML) between those with and without DS in Thailand. The medical records of AML patients aged 0-15 years treated in a major tertiary center in Southern Thailand between October 1978 and December 2019 were reviewed retrospectively. The overall (OS) and event-free survivals (EFS) rates were calculated using the Kaplan-Meier method. A total of 362 AML patients were included, of which 41 (11.3%) had DS. The mean age at diagnosis of the DS patients was 2.5 ± 1.9 years and most of them (90.2%) were under the age of five. The DS patients had lower initial white blood cell counts and peripheral blasts compared to the non-DS patients. The AML-M7 subtype was more common in the DS than in the non-DS patients (80.5% vs. 9.1%, p < 0.01, respectively). The 5-year OS and EFS rates of the DS patients were lower compared to the non-DS patients (12.9% vs. 20.5%, p = 0.05 and 13.7% vs. 18.4%, p = 0.03, respectively). DS patients had a significantly higher rate of early and treatment-related deaths compared to non-DS patients (30.3% vs. 13.5%, p < 0.01 and 39.4% vs. 19.5%, p = 0.02, respectively). Over the study period, there were a decrease in early death rate and an increase in survival rates of DS patients, which suggests that chemotherapy regimens and supportive care have improved over time.

Hyperleukocytosis in Childhood Acute Leukemia: Early Complications and Survival Outcomes.

Hyperleukocytosis and extreme hyperleukocytosis, defined as initial white blood cell counts greater than 100 × 109/L and 200 × 109/L, respectively, have been associated with unfavorable outcomes. This study aimed to determine the early complications and survival outcomes of childhood leukemia patients with hyperleukocytosis. The medical records of 690 children newly diagnosed with acute leukemia between January 1998 and December 2017 were retrospectively reviewed. The Kaplan-Meier method and log-rank test were used to assess and compare the survival outcomes. Multivariate Cox proportional hazards regression was used to determine associated risk factors for overall survival. We found that 16.6% of 483 childhood acute lymphoblastic leukemia (ALL) patients and 20.3% of 207 childhood acute myeloid leukemia (AML) patients had hyperleukocytosis at diagnosis. ALL patients with hyperleukocytosis had more early complications than those without hyperleukocytosis (p < 0.05). Among the ALL group, the 5-year overall survival rate for those with hyperleukocytosis was significantly lower than for those without hyperleukocytosis (37.2% vs. 67.8%, p < 0.0001), while the difference was not statistically significant in the AML group (19.0% vs. 30.2%, respectively, p = 0.26). Hyperleukocytosis (hazard ratio [HR]: 2.04), extreme hyperleukocytosis (HR: 2.71), age less than 1 year (HR: 3.05), age greater than 10 years (HR: 1.64), and male sex (HR: 1.37) were independently associated with poorer overall survival in childhood ALL patients. Extreme hyperleukocytosis (HR: 2.63) and age less than 1 year (HR: 1.82) were independently associated with poorer overall survival in AML patients. Hyperleukocytosis was associated with adverse survival outcomes in childhood leukemia.

Vitamin D Deficiency in Childhood Cancer Survivors: Results from Southern Thailand.

There is limited information on vitamin D deficiency among childhood cancer survivors (CSS), especially in tropical countries. The aims of this study are to determine the prevalence and risk factors for vitamin D deficiency in CCSs. This study was conducted at the long-term follow-up clinic for CCSs at Prince of Songkla University, Songkhla, Thailand. All CCSs who were followed up between January 2021 and March 2022 were enrolled. Demographic data, dietary dairy intake, average weekly duration of outdoor activities, total 25-hydroxyvitamin D [25(OH)D] levels, parathyroid hormone levels, and blood chemistry were collected. A total of 206 CCSs with a mean age at follow-up of 10.8 ± 4.7 years were included. The prevalence of vitamin D deficiency was 35.9%. Female gender (odds ratio (OR): 2.11, 95% CI: 1.08-4.13), obesity (OR: 2.01, 95% CI: 1.00-4.04), lack of outdoor activities (OR: 4.14, 95% CI: 2.08-8.21), and lower dietary dairy intake (OR: 0.59, 95% CI: 0.44-0.80) were independent risk factors for vitamin D deficiency. Vitamin D deficiency was common in CCSs and associated with female gender, obesity, lack of outdoor activities, and lower dietary dairy intake. Regular 25(OH)D screening should be established in long-term care to identify those who require vitamin D supplements.

Treatment outcomes in childhood acute lymphoblastic leukemia: 40-year experience from a single tertiary center in Thailand.

Studies on the long-term treatment outcomes of childhood acute lymphoblastic leukemia (ALL) in resource-limited countries are scarce. The purpose of this study was to assess the evolution of survival outcomes of pediatric ALL in a tertiary care center in Thailand over a 40-year period. We retrospectively reviewed the medical records of pediatric patients who were diagnosed with ALL and treated at our center between June 1979 and December 2019. We classified the patients into 4 study periods depending on the therapy protocol used to treat the patients (period 1: 1979-1986, period 2: 1987-2005, period 3: 2006-2013, and period 4: 2014-2019). The Kaplan-Meier method was used to determine overall and event-free survival (EFS) for each group. The log-rank test was used to identify statistical differences. Over the study period, 726 patients with ALL were identified, 428 boys (59%) and 298 girls (41%), with a median age at diagnosis of 4.7 years (range: 0.2-15 years). The study periods 1, 2, 3, and 4 had 5-year EFS rates of 27.6%, 41.6%, 55.9%, and 66.4%, and 5-year overall survival (OS) rates of 32.8%, 47.8%, 61.5%, and 69.3%, respectively. From periods 1 to 4, both the EFS and OS rates increased significantly (p <. 0001). Age, study period, and white blood cell (WBC) count were all significant prognostic indicators for survival outcomes. The OS of patients with ALL treated in our center improved significantly over time from 32.8% in period 1 to 69.3% in period 4.

Prevalence and risk factors of disseminated intravascular coagulation in childhood acute lymphoblastic leukemia.

BACKGROUND: Few studies have examined disseminated intravascular coagulation (DIC) in childhood acute lymphoblastic leukemia (ALL). Our aims were to evaluate the prevalence, risk factors and outcomes of DIC at ALL presentation and during induction chemotherapy. METHODS: The medical records of ALL patients aged <15 years were retrospectively reviewed. Logistic regression analysis was used to identify risk factors. The Kaplan-Meier method was used to depict survival. RESULTS: Of the 312 patients, 48 (15.4%) and 76 (24.4%) had DIC at presentation and during induction chemotherapy, respectively. Risk factors for DIC at presentation (OR and 95% CI) were antibiotics prior to admission 2.34 (1.17-4.89), white blood cell count ≥100 × 109/L 2.39 (1.04-5.72), platelets <100 × 109/L 5.44 (1.84-23.4) and high National Cancer Institute (NCI) risk 2.68 (1.08-6.62). Risk factors for DIC during induction chemotherapy were antibiotics prior to admission 1.86 (1.07-3.27), high peripheral blasts 1.01 (1.00-1.02) and transaminitis 2.02 (1.18-3.48). Five-year overall survival of patients who had DIC was significantly lower than those who did not (45.0% vs. 74.1%, p <0.001). CONCLUSION: Antibiotics prior to admission, hyperleukocytosis, thrombocytopenia and high NCI risk were risk factors of DIC at presentation. Antibiotics prior to admission, high peripheral blasts and transaminitis were risk factors of DIC during induction chemotherapy. IMPACT: There are only two studies, both published before 2000, evaluating risk factors of DIC in pediatric ALL patients without reporting outcomes. DIC was associated with lower remission and survival rates in pediatric ALL patients. We identified the risk factors of DIC at presentation as antibiotics prior to admission, hyperleukocytosis, thrombocytopenia and high NCI risk. The risk factors of DIC during induction chemotherapy were antibiotics prior to admission, high peripheral blasts and aspartate transaminitis. Pediatric ALL patients who have the aforementioned risk factors should be closely monitored for DIC secondary to infection, and early treatment with appropriate antimicrobial agents is recommended.

Transient abnormal myelopoiesis in Down syndrome: Experience of long term follow up from a single tertiary center in Thailand.

Transient abnormal myelopoiesis (TAM) is a unique disease occurring in Down syndrome (DS) infants from which most patients have spontaneous remission. This study aimed to evaluate the incidence and outcomes of TAM in a tertiary center in Thailand. We reviewed the records of 997 DS patients diagnosed between June 1993 and October 2019. From the 997 DS patients, 32 had been diagnosed with TAM. The incidence of TAM was 3.2% and an overall survival rate of 87.5%. A total of 2/28 who survived (7.1%) subsequently developed AML-DS at the ages of 2.1 and 4.5 years, respectively. The risk factors related with death included maternal multiparity, sepsis, skin bleeding, subcutaneous nodules, high WBC count, low hemoglobin, and elevated AST level.Abbreviations.

Relapsed Childhood Acute Myeloid Leukemia: Experience from a Single Tertiary Center in Thailand.

BACKGROUND: Few studies have examined survival outcomes in relapsed childhood acute myeloid leukemia (AML) in resource-limited countries. This study aimed to evaluate the prognostic factors and survival outcomes of relapsed childhood AML in Thailand. METHODS: The medical records of AML patients aged 0-15 years treated in a major tertiary center in Southern Thailand between December 1979 and December 2019 were reviewed retrospectively. The overall survival (OS) was calculated using the Kaplan-Meier method. RESULTS: A total of 316 AML patients were included and relapse occurred in 98 (31%) patients. Of these, 57 (58.2%) and 41 (41.8%) patients had early [≤1 year from first complete remission (CR1)] and late (>1 year from CR1) relapses, respectively. Only 54 (55.1%) patients received chemotherapy after relapse. The 3-year OS of all relapsed patients was 3.5%. The 3-year OS of patients with early and late relapse were 0% and 8.5%, respectively (p=0.002). The 3-year OS of patients who received chemotherapy and those who did not were 6.5% and 0%, respectively (p <0.0001). The median survival time of patients who did not receive chemotherapy was 1.7 months. The 3-year OS of patients who achieved second complete remission (CR2) and those who did not were 12.6% and 0%, respectively (p <0.001). CONCLUSION: The relapsed AML rate was 31% and the survival outcome was poor with a 3-year OS of 3.5%. The adverse prognostic factors were early relapse, failure to achieve CR2 and those who did not receive chemotherapy after relapse.

Relapsed Childhood Acute Lymphoblastic Leukemia: Experience from a Single Tertiary Center in Thailand.

BACKGROUND: The outcomes of relapsed childhood acute lymphoblastic leukemia (ALL) in developed countries have improved over time as a result of risk-adapted, minimal residual disease-directed therapy, hematopoietic stem cell transplantation, and immunotherapy. There are few studies that have examined survival in relapsed childhood ALL in resource-limited countries. Therefore, this study aimed to assess the prognostic factors and survival outcome of relapsed childhood ALL in a major tertiary center in Southern Thailand. METHODS: The medical records of patients with ALL aged <15 years between January 2000 and December 2019 were retrospectively reviewed. The Kaplan-Meier method was used to depict the overall survival (OS). RESULTS: A total of 472 patients with ALL were enrolled and relapsed ALL was found in 155 (32.8%) patients. Of these, 131 (84.5%) and 24 (15.5%) had B-cell and T-cell phenotypes, respectively. One hundred thirteen (72.9%) and 42 (27.1%) patients had early and late relapses, respectively. The most common site of relapse was bone marrow in 102 patients (65.8%). One hundred twenty-eight (82.6%) patients received treatment while 27 (17.4%) patients refused treatment. The 5-year OS of all relapsed patients was 11.9%. The 5-year OS among the patients with early relapse was significantly lower than in the patients with late relapse (5.3% vs. 29.1%, respectively, p <0.0001). Site and immunophenotype were not associated with survival of relapsed ALL. The median survival times among the patients who received and refused relapse chemotherapy were 11.8 and 3.1 months, respectively (p <0.0001). CONCLUSION: The relapse rate accounted for one third of patients with ALL with the 5-year OS of 12%. Early relapse and those who refused treatment were associated with poor survival outcome.

Musculoskeletal involvement in childhood leukemia: Characteristics and survival outcomes.

BACKGROUND : Childhood leukemia with musculoskeletal (MSK) involvement mimics various conditions, which consequently leads to diagnostic delays. The clinical implication of MSK involvement in this disease on survival outcomes is inconclusive. This study aimed to compare characteristics and survival outcomes between MSK and non-MSK involvement in childhood leukemia. METHODS: The medical records of children newly diagnosed with acute leukemia of an age under 15 years were retrospectively reviewed. Two-to-one nearest-neighbor propensity score-matching was performed to obtain matched groups with and without MSK involvement. The Kaplan-Meier method and log-rank test were then used to assess the effect of MSK involvement on survival outcomes. RESULTS: Of 1042 childhood leukemia cases, 81 (7.8%) children had MSK involvement at initial presentation. MSK involvement was more likely in children with acute lymphoblastic leukemia than acute myeloid leukemia (p < 0.05). Hematologic abnormalities were less frequent in the MSK involvement group (p < 0.05). The absence of peripheral blast cells was significantly higher in the MSK involvement group (17.3% vs 9.6%, p = 0.04). Normal complete blood counts with absence of peripheral blast cells were found 2.5% of the children with MSK involvement. By propensity score-matching for comparable risk groups of children with and without MSK involvement, the 5-year overall survival was not significantly different (48.2% vs 57.4%, respectively, p = 0.22), nor was event-free survival (43.3% vs 51.8%, respectively, p = 0.31). CONCLUSION: Childhood leukemia with MSK involvement had the characteristics of minimal or absent hematologic abnormalities and peripheral blast counts.

Predictive factors for adverse outcome of advanced-stage childhood lymphoblastic lymphoma: a single tertiary center retrospective study in Thailand.

Childhood lymphoblastic lymphoma (LL) is a highly aggressive neoplasm which has achieved favorable survival outcomes in many developed countries. However, few studies have reported treatment outcomes of childhood LL in resource-limited counties, nor has a prognostic scoring system been developed. The objectives of this study were to evaluate survival outcomes and identify prognostic factors associated with inferior outcomes of childhood LL in a referral center in March 1985 and April 2017 were retrospectively reviewed. Seventy-five advanced-stage LL patients were included, 47 (62.7%) of whom had stage IV at initial diagnosis. The 5-year DFS and OS rates were 44.6% and 44.7%, respectively. There were 3 significant prognostic factors associated with worse outcomes: presence of B symptoms, low albumin level < 3.5 g/dL and serum LDH level > 500 IU/L. From these three factors, we assigned a score of 1 for each and total scores of 0, 1, 2, and 3 could predict 5-year OS rates of 92.3%, 50.9%, 24.7% and 0%, respectively (p < 0.05). The survival of children in this study was lower than in other studies of advanced-stage childhood LL. We identified 3 adverse prognostic factors and developed a prognostic model for clinical use in advanced-stage childhood LL.

Successful Treatment of Gaucher Disease With Matched Sibling Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review.

BACKGROUND: Gaucher disease (GD) is the most common lysosomal storage disease and requires long-term enzyme replacement therapy (ERT), which is costly and inconvenient for resource-limited countries such as Thailand. The authors present the case of a 1-year-old boy who was diagnosed with GD type 1 with a homozygous mutation at c.1448 T>C (L444P). He was treated with ERT and matched sibling hematopoietic stem cell transplantation (HSCT) was performed 6 months after the ERT was initiated. At a 3-year follow-up after the HSCT, he had full engraftment and the Lyso-GL1 levels were also at an acceptable level, which indicated disease remission. In conclusion, the authors suggest HSCT for long-term remission of GD in children.

Outcome and Prognostic Factors of Childhood Hodgkin Disease: Experience From a Single Tertiary Center in Thailand.

In childhood, Hodgkin disease (HD) has an excellent outcome in developed countries. There are few studies on outcomes of HD from resource-limited countries. This study aimed to assess clinical outcomes and factors associated with survival rates of childhood HD in a tertiary care center in Thailand. We retrospectively reviewed the medical records of pediatric HD patients between March 1985 and August 2017. Seventy-two children diagnosed with HD were identified. Pretreatment clinical and laboratory factors were assessed by Cox regression analysis to predict event-free survival (EFS) and overall survival (OS). The overall 5-year EFS and OS rate was 70.7% and 75.5%, respectively. Multivariate analysis identified 3 factors predicting inferior EFS: high-risk group (stages III-B, IV-B), splenomegaly, and platelet count >400,000/µL. The prognostic markers were assigned a score of 1 for each factor. For a total score of 0, the 5-year EFS and OS rates were 95% and 86%; scores 2 to 3, 33% and 54%, respectively. In conclusion, our study identified 3 factors predicting inferior EFS. These adverse prognostic factors can be used in clinical practice for predicting outcomes in pediatric HD.

Effectiveness of Protocolized Sedation Utilizing the COMFORT-B Scale in Mechanically Ventilated Children in a Pediatric Intensive Care Unit.

Appropriate sedation in mechanically ventilated patients is important to facilitate adequate respiratory support and maintain patient safety. However, the optimal sedation protocol for children is unclear. This study assessed the effectiveness of a sedation protocol utilizing the COMFORT-B sedation scale in reducing the duration of mechanical ventilation in children. This was a nonrandomized prospective cohort study compared with a historical control. The prospective cohort study was conducted between November 2015 and August 2016 and included 58 mechanically ventilated patients admitted to the pediatric intensive care unit (PICU). All patients received protocolized sedation utilizing the COMFORT-B scale, which was assessed every 12 hours after intubation by a single assessor. The prospective data were compared with retrospective data of 58 mechanically ventilated patients who received sedation by usual care from November 2014 to August 2015. Fifty percent of 116 patients were male and the mean age was 22 months (interquartile range [IQR]: 6.6-68.4). Patients in the intervention group showed no difference in the duration of mechanical ventilation (median 4.5 [IQR: 2.2-10.5] vs. 5 [IQR: 3-8.8] days). Also, there were no significant differences in the PICU length of stay (LOS; median 7 vs. 7 days, p = 0.59) and hospital LOS (median 18 vs. 14 days, p = 0.14) between the intervention and control groups. The percentages of sedative drugs, including fentanyl, morphine, and midazolam, in each group were not statistically different. The COMFORT-B scale with protocolized sedation in mechanically ventilated pediatric patients in the PICU did not reduce the duration of mechanical ventilation compared with usual care.