Preventable Severe Thalassemia among Children

Abstract

This retrospective study analyzed 27 children with preventable severe thalassemia born to 24 at-risk couples between 1997 and 2017. The couples were categorized into two groups: the prenatal diagnosis (PND) group (n?=?8) and the non PND group (n?=?16). In the PND group, following comprehensive counseling on having a fetus with thalassemia, six couples decided to continue the pregnancy (n?=?6). Termination of the two remaining fetuses was excluded as the thalassemia status was reported at a gestational age of 24?weeks. In the non PND group, medical errors were found in the misdiagnosis of couples as non thalassemia carriers (n?=?4) and not offering PND to couples with known thalassemia carrier status when attending the antenatal clinic (ANC) (n?=?2). Additionally, parental ignorance was found in parents experiencing their own thalassemia, or that of their spouse or child (n?=?6). The remaining couples (n?=?4) with known carrier status either directly refused PND or were ineligible for it. A total of five divorces (5/24?=?20.8%) occurred in the PND (n?=?2) and the non PND (n?=?3) groups. Knowledge, beliefs, religion, experience of thalassemia, as well as the sex of the at-risk fetus all influenced parental decisions. Therefore, both medical personnel and parents are key in preventing new cases of thalassemia. Parents should be aware of the consequences of having children with severe thalassemia, while medical personnel should provide accurate carrier detection and PND.     

The second mini-transplant for unstable mixed chimerism within the first 100 days after hematopoietic stem cell transplant in severe thalassemia

Allogeneic HSCT is the only curative treatment for severe thalassemia disease. MC occurs in one-third of these patients within the first two months after HSCT; this is a major risk factor of graft rejection, especially when RHCs are more than 25%. There is still no consensus for the management of MC, especially in the early phase of HSCT. The DLI has also been described in the treatment of MC following HSCT for hemoglobinopathies, but its success is still not guaranteed. The second HSCT has been an approach used in an attempt to cure patients who reject their graft. Concern about toxicity of conditioning regimen, the second HSCT is usually delayed for at least a year after the first HSCT. We would like to demonstrate the successful use of the second mini-allogeneic HSCT in hemoglobin E/β-thalassemia with evidence of unstable MC in the first 100 days after allogeneic HSCT to prevent further graft loss after allogeneic HSCT.     

Genetic polymorphisms in Thai neonates with hyperbilirubinemia

Aim:  Polymorphisms of the UGT1A1 gene, SLCO1B1 gene and GST gene have been associated with significant hyperbilirubinemia. We would like to determine whether the variation of UGT1A1 gene, SLCO1B1 gene and GST gene may play a significant role in neonatal hyperbilirubinemia in Thai infants.
Methods:  Ninety-one study subjects (hyperbilirubinemic group) and 86 control subjects were studied.
Results:  The cause of neonatal hyperbilirubinemia could not be identified in 64 infants (70.3%), ABO blood group incompatibility in 14.3% and Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 8.8%. In the hyperbilirubinemic group, 23 of 91 (25.3%) infants demonstrated variant of UGT1A1 at nucleotides (nt) 211 as compared to 6 of 86 (7%) in the control group (p = 0.001). There were no significant differences between groups in the variants UGT1A1 at nt 686, SLCO1B1 gene at nt 388, 463 and the GST gene. Male infants with G-6-PD deficiency were associated with hyperbilirubinemia (21.2% vs. 4.8% in the control group) with an odds ratio (OR) of 5.37 (p =0.02). The relationship between G-6-PD and variant in UGT1A1 gene at nt 211 could not be determined.
Conclusion:  Thai infants with variant in the UGT1A1 at nt 211 or with G-6-PD deficiency are at higher risk for developing neonatal hyperbilirubinemia.     

Long-Term Outcomes of Modified St Jude Children’s Research Hospital Total Therapy XIIIB and XV Protocols for Thai Children With Acute Lymphoblastic Leukemia

BackgroundWe studied long-term outcomes and prognostic features of Thai children with acute lymphoblastic leukemia treated with modified St Jude Children’s Research Hospital (SJCRH) protocols.Patients and MethodsPediatric patients newly diagnosed with acute lymphoblastic leukemia were included. From 1997 to 2003, the first group received modified Total Therapy XIIIB (previous protocol). From 2004 to 2014, the latter had modified Total Therapy XV (current protocol).ResultsIn 250 patients, the event-free survival rates (± standard error) of the previous protocol (n = 95) were 82.8 ± 3.9%, 81.7 ± 4.0%, and 81.7 ± 4.0% at 5, 10, and 15 years, respectively; current protocol event-free survival rates (n = 155) were 84 ± 3.0%, 80.8 ± 3.4%, and 80.8 ± 3.4%, respectively. Previous protocol overall survival rates for the same years were 89.2 ± 3.2%, 84.8 ± 3.8%, and 84.8 ± 3.8%, and for the current protocol were 90 ± 2.5%, 86.9 ± 3.2%, and 83.7 ± 4.4%. Previous protocol relapses were 10.5% (10 patients), with 7 having isolated hematologic and 3 isolated/combined central nervous system relapses. Current protocol relapses were 9.7% (15 patients), with 7 having isolated hematologic, 6 isolated/combined central nervous system, and 2 extramedullary relapses. Patients with leukocyte counts over 100 × 10⁹/L and who had disease classified as high risk had worse event-free survival using the previous protocol. However, only initial leukocyte counts of ≥ 100 × 10⁹/L predicted adverse outcomes under the current protocol. Minimal residual disease positivity was a prognostic factor of worse overall survival only for previous protocol patients.ConclusionFavorable outcomes of childhood acute lymphoblastic leukemia occurred using adapted SJCRH protocols, perhaps because of multidisciplinary care teams and improved parent advocacy. Inferior outcomes might be prevented by addressing predictive factors to ameliorate monitoring and care.     

A population-based assessment of blood lead levels in relation to inflammation

Background

Some experimental and observational research suggests that inflammation may be an important mediator of lead toxicity. However, lead-induced inflammation has not been well-studied in non-occupationally exposed populations.

Methods

Using data for 9,145 individuals ≥40 years of age from the National Health and Nutrition Examination Survey 1999-2004, we assessed the association between blood lead levels (BLLs) and C-reactive protein (CRP), fibrinogen, and white blood cell (WBC) count via ordinal logistic regression. We also examined the interaction between BLL and gender in relation to the inflammatory markers.

Results

No evidence for an association between lead exposure and inflammatory markers was observed with odds ratios around or below the null. Although men but not women appeared to be at increased risk of lead-induced inflammation, no consistent dose-response patterns were observed across BLL quintiles.

Conclusion

Inflammation does not appear to be an important mediator of lead toxicity.