Enhancing outcomes of childhood acute lymphoblastic leukemia in workplace diversity in Thailand: multicenter study on behalf of the Thai Pediatric Oncology Group.

The Thai Pediatric Oncology Group (ThaiPOG) has adapted treatment regimens from the Children's Oncology Group (COG) to enhance outcomes for childhood acute lymphoblastic leukemia (ALL). This study examined the risk factors and treatment results of pediatric ALL in Thailand. This multicenter study included newly diagnosed children (< 18 years) with ALL in 19 centers between January 1, 2015, and December 31, 2019.

Nationwide Study of Factors Impacting Survival Outcome and Consequences in Children with Reactivation/Refractory Langerhans Cell Histiocytosis.

Background: Disease reactivation/refractory remains a major challenge in managing Langerhans cell histiocytosis (LCH). Outcomes and late sequelae should be explored.

Methods: A multi-institutional retrospective study was conducted to describe clinical characteristics, predictive factors, outcomes and late sequelae of pediatric reactivation/refractory LCH in Thailand.

Hemoglobin H Disease and Growth: A Comparative Study of DHbH and NDHbH Patients.

Background: Hemoglobin H disease HbH, a hemoglobinopathy resulting from abnormal alpha globin genes, is classified into two categories: deletional HbH DHbH and non-deletional HbH NDHbH. The alpha-mutation genotypes exhibit a range of clinical anemias, which differentially impact patient growth.

Objectives: This retrospective study assessed the growth of HbH patients at Siriraj Hospital, Mahidol University.

Polymorphisms and the Incidence of Toxicities in Children with Acute Lymphoblastic Leukemia.

Background: 6-Mercaptopurine (6-MP), a thiopurine agent, is a essential medication for treating pediatric acute lymphoblastic leukemia (ALL). However, its side effects of neutropenia and hepatotoxicity might interrupt treatment, resulting in poor outcomes. Inosine triphosphate pyrophosphatase (), an enzyme in the thiopurine pathway, may prevent the accumulation of toxic thiopurine metabolites.

Outcomes of Overt and Non-overt Disseminated Intravascular Coagulation Using the ISTH DIC Scoring System in Children: A Single-Center Study.

Background: Several disseminated intravascular coagulation (DIC) scoring systems are used for prognosticating the clinical outcomes of patients with DIC. However, research on children is scarce. Therefore, this study compared the clinical outcomes of overt and non-overt DIC using the International Society on Thrombosis and Hemostasis (ISTH) DIC scoring system.

Ototoxicity and long-term hearing outcome in pediatric patients receiving cisplatin.

Background: Hearing is essential in child development. Cisplatin which is a common chemotherapy used in many pediatric solid-tumor protocols cause various degrees of ototoxicity. Several risk factors for cisplatininduced ototoxicity have been reported, including race and age.

Long-Term Effectiveness, Safety, and Tolerability of Twice-Daily Dosing with Deferasirox in Children with Transfusion-Dependent Thalassemias Unresponsive to Standard Once-Daily Dosing.

Background: Patients with transfusion-dependent thalassemia TDT risk iron overload and require iron chelation therapy. Second-line therapy is warranted for patients demonstrating poor chelation responses.

Patients And Methods: We retrospectively studied the serum-ferritin (SF), and liver-iron-concentration (LIC) outcomes of patients with TDT treated with twice-daily dosing of deferasirox (TDD-DFX) > 24 months, after failing to respond to once-daily deferasirox (OD-DFX).

A Comparison of the Clinical Outcomes of Haploidentical Transplantation and Other Graft Sources in Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis.

Background: Most likely due to the availability of potential stem cell sources, there appears to be a growing usage of haploidentical (haplo) donors for cases of acute lymphoblastic leukemia involving high-risk features or relapse.

Patients And Methods: This study compared the outcomes of stem cell transplantations (SCTs) using haplo and other stem cell sources, namely, matched sibling donors (MSDs), matched unrelated donors (MUDs), and cord blood transplantations (CBTs). Literature searches were conducted of the MEDLINE and Embase databases from inception to December 2020.

Antifungal Prophylaxis with Posaconazole versus Fluconazole in Children with Neutropenia Following Allogeneic Hematopoietic Stem Cell Transplantation: Single Center Experience.

Background: Invasive fungal diseases (IFDs) are common and contribute to mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). The relative efficacies of posaconazole (POS) and fluconazole (FLU) as primary antifungal prophylaxes are uncertain.

Methods: A retrospective study was performed on children treated with allogeneic HSCT who received POS or FLU during the early neutropenic period.

Invasive Fungal Diseases in Children with Acute Leukemia and Severe Aplastic Anemia.

Although the outcomes of childhood leukemia and severe aplastic anemia (SAA) have improved, infectious complications are still the major concern. Particularly worrisome are invasive fungal diseases (IFDs), one of the most common causes of infectious-related deaths in patients with prolonged neutropenia. A retrospective study was conducted of IFDs in pediatric patients with newly diagnosed or relapsed acute leukemia, or with SAA, at Siriraj Hospital, Mahidol University, Thailand.

GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma - assessing tumor and T cell interaction.

A novel disialoganglioside 2 (GD2)-specific chimeric antigen receptor (CAR)-modified T cell therapy against retinoblastoma (RB) were generated. GD2-CAR consists of a single-chain variable fragment (scFv) derived from a monoclonal antibody, hu3F8, that is linked with the cytoplasmic signaling domains of CD28, 41BB, a CD3ζ, and an inducible caspase 9 death fusion partner. GD2 antigen is highly expressed in Y79RB cell line and in several surgical RB tumor specimens.

Clinical outcomes and prognosis of Thai retinoblastoma patients.

Background: Retinoblastoma (RB) outcomes in Thailand are unfavorable compared to those of developed countries. This study aims to determine whether the clinical outcomes of patients with RB significantly improved after the implementation of new therapeutic approaches and which clinical factors affect survival and globe-saving outcomes.

Methods: The medical records of patients newly diagnosed with RB and treated at Siriraj Hospital between January 2005 and December 2018 were reviewed retrospectively.

Using of deferasirox and deferoxamine in refractory iron overload thalassemia.

Background: Iron overload is a major complication of transfusion-dependent thalassemia (TDT) and requires iron chelation (IC) therapy. However, a combination therapy may be required for patients responding poorly to monotherapy.

Methods: Nine TDT patients previously treated with IC were enrolled; five patients were previously treated with deferasirox (DFX) twice daily.

Impact of splenectomy on outcomes of hematopoietic stem cell transplantation in pediatric patients with transfusion-dependent thalassemia.

Background: The role of splenectomy prior to hematopoietic stem cell transplantation (HSCT) is controversial. Only few studies compared the outcomes of splenectomized and nonsplenectomized children with transfusion-dependent thalassemia (TDT) undergoing allogeneic HSCTs.

Methods: A retrospective analysis was undertaken on a transplantation cohort of TDT patients; August 1987-December 2014 to compare transplant outcomes between splenectomized and nonsplenectomized groups.

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.

Prevalence and Clinical Outcome of Philadelphia-Like Acute Lymphoblastic Leukemia: Systematic Review and Meta-analysis.

Background: The presence of Philadelphia (Ph)-like ALL among patients with acute lymphoblastic leukemia (ALL) may indicate a poor prognosis similar to Ph ALL, although the data are still inconclusive and the prevalence of Ph-like ALL varied considerably across studies.

Patients And Methods: We performed a systematic review and meta-analysis in order to identify all cohort studies of patients with ALL that reported the prevalence of Ph-like ALL and to summarize their results together. The pooled prevalence and rate were calculated by the DerSimonian-Laird random-effect model with double arcsine transformation.

Effect of NUDT15 on incidence of neutropenia in children with acute lymphoblastic leukemia.

Background: 6-Mercaptopurine (6-MP) is considered the backbone of therapy in the maintenance phase of acute lymphoblastic leukemia (ALL). Gene polymorphisms involved in thiopurine degradation are predictors of toxicity in patients treated with 6-MP. We investigated the effects of nucleoside diphosphate linked moiety X (nudix) type motif 15 (NUDT15) polymorphism NUDT15c.

Outcomes of pediatric retinoblastoma treated with ICEV regimen: A single-center study.

Retinoblastoma is the most common intraocular malignancy in children. The aim of this study was to investigate the efficacy and toxicity of combination ifosfamide, carboplatin, etoposide, and vincristine (ICEV) in advanced-stage pediatric retinoblastoma [International Classification of Retinoblastoma (ICRB) group D or E], and in ICRB group C in the second eye in simultaneously treated bilateral retinoblastoma. The medical records of retinoblastoma patients treated with concurrent ICEV regimen and focal therapy were retrospectively reviewed.

Hematologic Malignancies Associated With Mediastinal Germ Cell Tumors: 10 Years' Experience at Thailand's National Pediatric Tertiary Referral Center.

Mediastinal germ cell tumor (MGCT), which accounts for 1% to 3% of extragonadal germ cell tumors, has unique manifestations; it is associated with several types of hematologic malignancy, particularly myeloid neoplasm. The aim of this study was to report the 10-year incidence, clinical characteristics, and outcomes of MGCT at Thailand's national pediatric tertiary referral center. This retrospective study included patients diagnosed with MGCT at the Department of Pediatrics, Siriraj Hospital during 2005 to 2014.

Evaluation of artemisinins for the treatment of acute myeloid leukemia.

Purpose: Investigate antileukemic activity of artemisinins, artesunate (ART), and dihydroartemisinin (DHA), in combination with cytarabine, a key component of acute myeloid leukemia (AML) chemotherapy using in vitro and in vivo models.

Methods: Using ten human AML cell lines, we conducted a high-throughput screen to identify antimalarial agents with antileukemic activity. We evaluated effects of ART and DHA on cell viability, cytotoxicity, apoptosis, lysosomal integrity, and combination effects with cytarabine in cell lines and primary patient blasts.

Bisphosphonate Therapy for Refractory Langerhans Cell Histiocytosis: A Case Report.

Although patients diagnosed as Langerhans cell histiocytosis (LCH) with bone lesion initially respond well to treatment, some may experience relapse or refractory disease. Pamidronate, a potent N-bisphosphonate, has been used in several primary bone diseases, benign bone tumors, and metastatic bone cancers. The mechanism includes an inhibitory effect on osteoclast activity by decreasing development and recruitment of osteoclast progenitors and promoting osteoclast apoptosis.

Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia.

FLT3 kinase internal tandem duplication (ITD) mutations are common in acute myeloid leukemia (AML) and are associated with poor clinical outcomes. Although initial responses to FLT3 tyrosine kinase inhibitors (TKIs) are observed in FLT3-ITD-positive patients, subsequent relapse often occurs upon acquisition of secondary FLT3 kinase domain (KD) mutations, primarily at residues D835 and F691. Using biochemical assays, we determined that crenolanib, a novel TKI, demonstrates type I properties and is active against FLT3 containing ITD and/or D835- or F691-activating mutations.

Emergence of polyclonal FLT3 tyrosine kinase domain mutations during sequential therapy with sorafenib and sunitinib in FLT3-ITD-positive acute myeloid leukemia.

Purpose: To evaluate the clinical activity of sequential therapy with sorafenib and sunitinib in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD)-positive acute myelogenous leukemia (AML) and monitor the emergence of secondary FLT3 tyrosine kinase domain (TKD) mutations during treatment.

Experimental Design: Six children with relapsed/refractory AML were treated with sorafenib in combination with clofarabine and cytarabine, followed by single-agent sorafenib if not a candidate for transplantation. Sunitinib was initiated after sorafenib relapse.