Hypothyroidism in children with Hb E/ß-thalassemia compared between those who received regular transfusion and those who underwent hematopoietic stem cell transplantation.

The studies of hypothyroidism in children with transfusion-dependent hemoglobin E/ß-thalassemia (TDT), especially in those who underwent hematopoietic stem cell transplantation (HSCT) are limited. We performed a longitudinal retrospective analysis of thyroid function test (TFT) results among TDT patients aged <25 years who received regular transfusion compared to those who underwent HSCT in Faculty of Medicine Siriraj hospital, Thailand during October 2003 to March 2019. Fifty patients (23 TDT, 27 HSCT) were included. The mean age at the last follow-up was 20.1 ± 2.8 vs. 14.5 ± 4.61 years, respectively. The median age at HSCT was 6 (range: 1.9-13.7) years. The prevalence of hypothyroidism among TDT and post-HSCT was 47.8% and 52.2%, respectively. No study patients showed symptoms or signs of hypothyroidism. Subclinical hypothyroidism was the most common type (63.6% of TDT, and 100% of post-HSCT). We found persistent hypothyroidism in 30.4% of TDT, and in 22.2% of post-HSCT. Thyroxine was given in 1 TDT patient with overt hypothyroidism, and in 3 of 6 post-HSCT patients with persistent subclinical hypothyroidism. The ex-thalassemia patients who underwent HSCT after the age of 10 years had a significantly higher risk of post-HSCT hypothyroidism compared to those who underwent HSCT at the age ≤10 years (hazard ratio: 12.01, 95% confidence interval: 1.65-87.41; p = 0.014). In conclusion, hypothyroidism was found to be common in both TDT and post-HSCT patients. Subclinical hypothyroidism without symptoms and signs was the most common type, and was diagnosed only by TFT screening. Long-term regular surveillance of TFT should be performed in both groups of patients.

Treatment outcomes among high-risk neuroblastoma patients receiving non-immunotherapy regimen: Multicenter study on behalf of the Thai Pediatric Oncology Group.

BACKGROUND: Neuroblastoma is the most common extracranial malignant solid tumor during childhood. Despite intensified treatment, patients with high-risk neuroblastoma (HR-NBL) still carry a dismal prognosis. The Thai Pediatric Oncology Group (ThaiPOG) proposed the use of a multimodality treatment to improve outcomes of HR-NBL in non-immunotherapy settings. METHODS: Patients with HR-NBL undergoing ThaiPOG protocols (ThaiPOG-NB-13HR or -18HR) between 2013 and 2019 were retrospectively reviewed. Patient demographic data, treatment modalities, outcomes, and prognostic factors were evaluated and analyzed. RESULTS: A total of 183 patients with HR-NBL undergoing a topotecan containing induction regimen were enrolled in this study. During the consolidation phase (n = 169), 116 patients (68.6%) received conventional chemotherapy, while 53 patients (31.4%) underwent hematopoietic stem cell transplantation (HSCT). The 5-year overall survival (OS) and event-free survival (EFS) were 41.2% and 22.8%, respectively. Patients who underwent HSCT had more superior 5-year EFS (36%) than those who received chemotherapy (17.1%) (p = .041), although they both performed similarly in 5-year OS (48.7% vs. 39.8%, p = .17). The variation of survival outcomes was observed depending on the number of treatment modalities. HSCT combined with metaiodobenzylguanidine (MIBG) treatment and maintenance with 13-cis-retinoic acid (cis-RA) demonstrated a desirable 5-year OS and EFS of 65.6% and 58.3%, respectively. Poorly or undifferentiated tumor histology and cis-RA administration were independent factors associated with relapse and survival outcomes, respectively (p < .05). CONCLUSION: A combination of HSCT and cis-RA successfully improved the outcomes of patients with HR-NBL in immunotherapy inaccessible settings.

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. The dose of DFX was 20-40 mg/kg/day, while the dose of deferoxamine (DFO) was 18-40 mg/kg/day for 3-6 days/week. RESULTS: At the 6- and 12-month time points, six and eight patients demonstrated decreased serum ferritin levels, with median reductions of 707 ng/mL (range, 1,653-5,444 ng/mL) and 1,129 ng/mL (range, 1,781-7,725 ng/mL) compared to the baseline, respectively. Eight patients also had a reduced liver iron concentration (LIC), with a median reduction of 3.9 mg/g dry wt (range, 8.3-11.1 mg/g dry wt). Of the five patients treated with DFX twice daily, four responded to combination therapy. All responsive patients could finally stop DFO after the decline in LIC. Moreover, there were no treatment-related complications. CONCLUSION: The combination of DFX and DFO proved to be effective and without significant toxicities for TDT patients who had been unresponsive to standard IC therapy. Further studies with a larger cohort size and long-term follow-up are warranted to elucidate the efficacy of the combination.

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. Clinical data, treatments, and outcomes were collected and analyzed. RESULTS: In 194 eyes (144 patients), leukocoria was the most common presenting feature (76.8%); 129 (66.5%) eyes were staged in group E of the International Classification of Intraocular Retinoblastoma. Of the 149 enucleated eyes, 35 had high-risk histopathological features, mostly choroidal invasion; 45 eyes (23.2%) could be salvaged. The 5-year overall survival rate was 90.3%, an improvement compared to the previous study. The 5-year enucleation-free survival rates of Groups A and B, C, D and E were 100%, 83.1%, 36.7% and 16.6% respectively. Factors associated with a lower survival rate were interval from symptom onset to diagnosis >3 months (hazard ratio (HR): 5.8: 95% confidence interval (CI): 1.637, 20.579) and buphthalmos (HR: 12.57: 95% CI: 3.936, 40.153). Factors associated with high-risk features were secondary glaucoma (HR: 11.016: 95% CI: 1.24, 98.10) and pseudohypopyon (HR: 14.110: 95% CI: 2.16, 92.05). CONCLUSIONS: Survival rates and globe-saving rates appear to have improved; however, advanced-stage presentation remains the major hindrance. Further studies with a larger cohort and longer follow-up are warranted.

Therapeutic drug monitoring of intravenous busulfan in Thai children undergoing hematopoietic stem cell transplantation: A pilot study.

Busulfan (Bu) is commonly used in myeloablative conditioning regimens for children undergoing hematopoietic stem cell transplantation. The standard target area under the concentration-time curve (AUC) of Bu is approximately 900-1500 µM min. In previous studies using five fixed doses (0.8-1.2 mg/kg) for Bu without dose adjustment, 75% patients achieved the target AUC. The aim of this pilot study was to determine the percentage of target AUC for intravenous (IV) Bu in Thai children. IV Bu was administered every 6 h over 16 doses. Blood samples were collected for pharmacokinetic (PK) analysis after the first, ninth, and thirteenth doses of Bu. Seven patients (2-14 years; median 6 years) were diagnosed with thalassemia (n = 4), acute myeloid leukemia (n = 2), and pure red cell aplasia. Three, two, and two patients received Bu at 1.1, 1.2, and 0.8 mg/kg, respectively. The AUC of Bu varied from 292-1714 µM min (median = 804). Nine (42.86%), eleven (52.38%), and one (4.76%) AUC values were within, below, and above the target, respectively. The median (range) Bu clearance was 5.93 (1.91-14.65) mL/min/kg. In this study, 42.86% AUC value achieved the target, which was lower than that in previous studies. Therapeutic drug monitoring (TDM) of Bu should be considered in Thai children receiving five fixed doses of IV Bu, and dose adjustment should be performed as necessary. Further PK studies for Bu with a larger sample size are warranted for confirming the necessity of TDM in every step dose of Bu.(Trial registration numbers; TCTR20190528003).

Hematopoietic Stem Cell Transplantation for Severe Thalassemia Patients from Haploidentical Donors Using a Novel Conditioning Regimen.

Patients with severe thalassemia commonly have a survival that is significantly shorter than that of the general population. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only established treatment that is potentially curative, but it is limited by the availability of donors and the medical condition of the patient. To expand the donor pool to include haploidentical related donors, we introduced a program consisting of a pharmacologic pretransplant immune suppression phase (PTIS) and 2 courses of dexamethasone and fludarabine, followed by pretransplant conditioning with fludarabine-i.v. busulfan and post-transplant graft-versus-host disease (GVHD) prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil. We transplanted 83 consecutive transfusion-dependent patients with thalassemia (median age, 12 years; range, 1 to 28 years) with a minimum follow-up of 6 months (median, 15 months; range, 7 to 53 months); the 3-year projected overall and event-free survival is over 96%, and there have been no secondary graft failures. Of the first 31 patients, we had 2 graft failures, both of them occurring in patients with extremely high titers of anti-donor-specific HLA antibodies (anti-DSAs), but after adjusting the PTIS to include bortezomib and rituximab for patients with high titers of anti-DSAs and using pharmacologic dose guidance for busulfan, we had no graft failures in the last 52 patients. Six (7%) of 83 patients developed severe GVHD. We conclude that this is a safe and efficacious approach to allogeneic SCT in thalassemia, yielding results comparable to those available for patients with fully matched donors.

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.

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. RESULTS: Ninety-six transplants in 86 TDT patients were analyzed. Sixteen patients were splenectomized before HSCTs. The splenectomized patients were significantly older (8.0 ± 1.9 vs 4.7 ± 0.6 years; P = 0.001), had larger livers and spleens (P = 0.001), and had a significantly shorter neutrophil engraftment time (absolute neutrophil count > 500/mm3 ; 15.0 ± 2.3 vs 19.2 ± 1.3 days; P = 0.004). Graft rejection occurred in 13.8% of the nonsplenectomized group, but not among the splenectomized patients. Though the splenectomized group's mortality rate was higher (25.0% vs 8.8%), this was not statistically significant (P = 0.491). The main causes of death in both groups were severe infections. The five-year overall survival (OS) rate was better for the nonsplenectomized group (91.78% vs 75.00%; P = 0.06). CONCLUSIONS: Although splenectomies prior to HSCT for the TDT patients in our cohort were associated with faster neutrophil engraftments and lower rejection rates, they did not produce significantly better OS or affect the mortality. As the splenectomies did not provide any distinct advantages, this procedure should not be routinely performed as a pre-HSCT regimen for TDT patients with splenomegaly. Better pre-HSCT preparation for TDT patients, including early and adequate blood transfusions to avoid splenomegaly, is recommended.

Clinical outcomes and prognostic factors to predict treatment response in high risk neuroblastoma patients receiving topotecan and cyclophosphamide containing induction regimen: a prospective multicenter study.

BACKGROUND: Neuroblastoma is the most common extra-cranial solid tumor among children. Despite intensive treatment, patients with advanced disease mostly experience dismal outcomes. Here, we proposed the use of topotecan and cyclophosphamide containing induction regimen as an upfront therapy to high risk neuroblastoma patients. METHODS: Patients with high risk neuroblastoma undergoing ThaiPOG high risk neuroblastoma protocol from 2016 to 2017 were studied. All patients received 6 cycles of induction regimen consisting of 2 cycles topotecan (1.2 mg/m2/day) and cyclophosphamide (400 mg/m2/day) for 5 days followed by cisplatin (50 mg/m2/day) for 4 days combined with etoposide (200 mg/m2/day) for 3 days on the third and fifth cycles and cyclophosphamide (2100 mg/m2/day) for 2 days combined with doxorubicin (25 mg/m2/day) and vincristine (0.67 mg/m2/day) for 3 days on the fourth and sixth cycles. Treatment response after the 5th cycle before surgery and treatment-related toxicities after each topotecan containing induction cycle were evaluated. Relevant prognostic factors were analyzed to measure the treatment response among those patients. RESULTS: In all, 107 high risk neuroblastoma patients were enrolled in the study. After the 5th cycle of induction regimen, the patients achieved complete response (N = 2), very good partial response (N = 40), partial response (N = 46) and mixed response (N = 19). None of the patients experienced stable disease or disease progression. The most significant prognostic factor was type of healthcare system. The most common adverse effect was febrile neutropenia followed by mucositis, diarrhea and elevated renal function. CONCLUSION: The topotecan and cyclophosphamide containing induction regimen effectively provides favorable treatment response. The regimen is well tolerated with minimal toxicity among patients with high risk neuroblastoma in Thailand.

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.415C>T on neutropenia incidence, dose adjustment for 6-MP, and survival rates in Thai children with ALL. METHODS: Children diagnosed with ALL who received 6-MP in the maintenance phase of treatment, in 2005-2016, were retrospectively enrolled. RESULTS: The subjects consisted of 102 patients (median age, 5.2 years; 58 boys). On genetic testing 78, 22, and two patients were normal (CC), heterozygous (CT), and homozygous (TT), respectively. The incidence of neutropenia at 3 months was significantly higher in the CT/TT than CC polymorphism groups (OR, 12; 95%CI: 3.781-38.085, P < 0.001). The mean dose of 6-MP at 3, 6, and 12 months was significantly lower in the CT/TT versus the CC group (P < 0.001). The 5 year overall survival (OS) rate for CC was 80.4%, and for CT/TT, 95.5% (P = 0.34). The 5 year event-free survival (EFS) for CC and CT/TT was 75.1% and 85.7%, respectively (P = 0.17). After adjusted risk classification, no significant differences were observed for OS or EFS between the CC and CT/TT groups. CONCLUSION: Patients harboring the CT/TT polymorphism of NUDT15 had a significantly higher incidence of neutropenia during the first 3 months of maintenance, resulting in significantly lower doses of 6-MP.

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. The ICEV treatment protocol was, as follows: ifosfamide 1800 mg/m2 on Days 1-3; MESNA 600 mg/m2 on Days 1-3; carboplatin 560 mg/m2 on Day 1; etoposide 150 mg/m2 on Days 1-3; and vincristine 1.5 mg/m2 on Day 1. Of 16 retinoblastoma patients, 13 had bilateral disease. Seven first eyes in bilateral disease that were enucleated prior to ICEV therapy were excluded. Twenty-two eyes were finally included (six group C, six group D, and ten group E). Median follow-up was 3.4 years, and the median number of ICEV courses was 7. Fifteen globes could be salvaged, 12 responded to ICEV (six group C, five group D, and one group E), and three unresponsive eyes could be salvaged with external beam radiation therapy (EBRT). Enucleation-free and relapse-free survival was 68.2 and 54.5%, respectively. The results of this study suggest ICEV as an alternative therapeutic approach for globe salvage in pediatric retinoblastoma, especially in ICRB groups C and D with manageable acute toxicity. Further study in larger cohort is needed to confirm the effectiveness of treatment.

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. Eight patients (all male) were diagnosed with MGCT. Five of 8 patients were found to have hematologic abnormalities. Three patients were diagnosed with acute myeloid leukemia (AML) (one patient with M1, another having M7, and the other with M0). Another patient had mixed MGCT with mediastinal myeloid sarcoma (MMS). The other patient had malignancy-associated hemophagocytic lymphohistiocytosis syndrome (M-HLH). Isochromosome 12p was detected in 3 patients (AML [2], mixed MGCT/MMS [1]). Four of 5 patients with hematologic abnormalities died of hematologic abnormalities or treatment complication (AML [3], M-HLH [1]). One patient with mixed MGCT/MMS survived with chemotherapy. All patients with AML and MMS were nonseminomatous MGCT and the onset of myeloid malignancies were within 1 year after the diagnosis of MGCT. Associated hematologic malignancies should be suspected in MGCT with abnormal blood count or hematologic symptoms. Isochromosome 12p was the most common cytogenetic finding in MGCT-associated myeloid malignancies patients. Those with nonseminomatous MGCT should have their blood count carefully monitored especially during the first year after the diagnosis of MGCT. Better treatment alternatives for MGCT with associated hematologic malignancies are warranted to ameliorate adverse outcomes.

Mutations in Kruppel-like factor 1 cause transfusion-dependent hemolytic anemia and persistence of embryonic globin gene expression.

In this study, we report on 8 compound heterozygotes for mutations in the key erythroid transcription factor Krüppel-like factor 1 in patients who presented with severe, transfusion-dependent hemolytic anemia. In most cases, the red cells were hypochromic and microcytic, consistent with abnormalities in hemoglobin synthesis. In addition, in many cases, the red cells resembled those seen in patients with membrane defects or enzymopathies, known as chronic nonspherocytic hemolytic anemia (CNSHA). Analysis of RNA and protein in primary erythroid cells from these individuals provided evidence of abnormal globin synthesis, with persistent expression of fetal hemoglobin and, most remarkably, expression of large quantities of embryonic globins in postnatal life. The red cell membranes were abnormal, most notably expressing reduced amounts of CD44 and, consequently, manifesting the rare In(Lu) blood group. Finally, all tested patients showed abnormally low levels of the red cell enzyme pyruvate kinase, a known cause of CNSHA. These patients define a new type of severe, transfusion-dependent CNSHA caused by mutations in a trans-acting factor (Krüppel-like factor 1) and reveal an important pathway regulating embryonic globin gene expression in adult humans.

Hemophagocytic lymphohistiocytosis following dengue hemorrhagic fever in Hb H/Hb Constant Spring patient.

Infection-associated hemophagocytic syndrome (IAHS), a secondary form of hemophagocytic lymphohistiocytosis (HLH), has been found following several types of infections and can be fatal. We report herein a case of IAHS following dengue infection in a 14-year-old patient with underlying α-thalassemia syndrome (non-deletional Hb H/Hb Constant Spring disease). He developed prolonged fever, thrombocytopenia, and progressive splenomegaly. Further investigations indicated hyperferritinemia, and increased reactive histiocytes with hemophagocytic activity in the bone marrow. He responded promptly to dexamethasone and i.v. immune globulin. Physicians should be aware of this condition, especially in countries where both dengue hemorrhagic fever and thalassemia are prevalent. The fatal outcome of IAHS can be prevented with prompt appropriate treatment.

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. Herein, we introduce a seven-month-old Thai girl who was diagnosed as multiple-relapse LCH with refractory bone lesions and was treated with standard and salvage steroid-based therapies. After receiving two courses of intravenous pamidronate, she had marked clinical and radiographical improvement without any adverse events. She has been in remission for two years after receiving six courses of therapy. This report supports the efficacy ofpamidronate in LCH-related bone lesions, but further studies in large cohort are warranted.

Outcomes of thalassemia patients undergoing hematopoietic stem cell transplantation by using a standard myeloablative versus a novel reduced-toxicity conditioning regimen according to a new risk stratification.

Improving outcomes among class 3 thalassemia patients receiving allogeneic hematopoietic stem cell transplantations (HSCT) remains a challenge. Before HSCT, patients who were ≥ 7 years old and had a liver size ≥ 5 cm constitute what the Center for International Blood and Marrow Transplant Research defined as a very high-risk subset of a conventional high-risk class 3 group (here referred to as class 3 HR). We performed HSCT in 98 patients with related and unrelated donor stem cells. Seventy-six of the patients with age < 10 years received the more conventional myeloablative conditioning (MAC) regimen (cyclophosphamide, busulfan, ± fludarabine); the remaining 22 patients with age ≥ 10 years and hepatomegaly (class 3 HR), and in several instances additional comorbidity problems, underwent HSCT with a novel reduced-toxicity conditioning (RTC) regimen (fludarabine and busulfan). We then compared the outcomes between these 2 groups (MAC versus RTC). Event-free survival (86% versus 90%) and overall survival (95% versus 90%) were not significantly different between the respective groups; however, there was a higher incidence of serious treatment-related complications in the MAC group, and although we experienced 6 graft failures in the MAC group (8%), there were none in the RTC group. Based on these results, we suggest that (1) class 3 HR thalassemia patients can safely receive HSCT with our novel RTC regimen and achieve the same excellent outcome as low/standard-risk thalassemia patients who received the standard MAC regimen, and further, (2) that this novel RTC approach should be tested in the low/standard-risk patient population.

Variable genotype-phenotype correlations in patients with a rare nondeletional α-thalassemia; Hb Pak Num Po (HBA1: c.396_397insT).

Transfusion-dependent Hb H disease is rarely reported. In the majority of patients, it is caused mainly by α(0)-thalassemia from deletions of 2 linked α-globin genes and nondeletional mutations. Previously, we had described 2 unrelated Thai patients with this condition because of compound heterozygosity of SEA-type deletion (--SEA/) and a novel nucleotide mutation: a thymine insertion at codon 131 of the α1 gene, namely, Hb Pak Num Po (Hb PNP, αα(PNP)). We herein describe the identification of 4 additional patients with Hb PNP with a broader genotype/phenotype spectrum and provide an overview of clinical management approaches including stem-cell transplantation.

Primary intrarenal/perirenal neuroblastoma mimicking Wilms' tumor at presentation in a 5-year-old girl: a case report from Siriraj hospital.

Primary intrarenal/perirenal neuroblastoma (NB) is NB that primarily arises in intrarenal and/or perirenal regions. Regarding its location, this tumor can mimic Wilms' tumor a more common pediatric renal tumor at presentation. Owing to diference in clinical management andprognosis, it is crucial to distinguish primary intrarenal/perirenal NB from Wilms' tumor at the time of diagnosis. Recognition of its characteristic features, which are distinctive from its adrenal counterpart, is helpful to guide to the correct diagnosis and proper treatment. However,; due to its rarity with less than 100 cases described in English literatures, the characteristics of primary intrarenal/perirenal NB have not been widely studied The authors, therefore, report this case of primary intrarenal/perirenal NB, which occurred in right kidney of a 5-year-old Thai girl in order to illustrate the characteristic features of this tumor To the authors'knowledge, this case is the first case ofprimary intrarenal/perirenal NB that has been reported in Thailand

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. RESULTS: In all, 47 patients were studied, 25 (53.2%) patients had disease reactivation and 22 (46.8%) patients had refractory LCH. The median reactivation and refractory time were 1.59 and 0.33 years from diagnosis, respectively (p <0.001). The most common site of reactivation/refractory was the bone (n = 26, 55%), and 20 (42.6%) patients developed late sequelae. The 5-year overall survival (OS) was 76.1%. Patients with reactivation and refractory LCH performed similarly in 5-year OS (88% vs. 63%, p = 0.055). Prognostic factors associated with mortality were liver, spleen, hematopoietic system and lung reactivation (p <0.05). Lung reactivation was the only independent risk factor associated with the survival outcome (p = 0.002). CONCLUSIONS: The outcomes of pediatric patients between reactivation and refractory LCH in Thailand were similarly desirable and mortality was minimal although late sequelae may evolve. Pulmonary reactivation/refractory was an independent risk factor associated with survival.

Allogeneic stem cell transplantation for children with acquired severe aplastic anaemia: a retrospective study by the Viva-Asia Blood and Marrow Transplantation Group.

We retrospectively analysed the outcomes of 127 children with acquired severe aplastic anaemia (SAA) who had received haematopoietic stem cell transplantation (HSCT) between 2000 and 2011 in one of the 10 Asia Pacific institutions. Fifty-three were matched sibling donor (MSD) and 74 were alternative donor (AD), including 22 matched unrelated donor, 32 mismatched unrelated donor and 20 mismatched related donor. With a median follow up 45.5 months (13-139) and when compared to the MSD group, AD recipients had more grade II-IV acute graft-versus-host disease (aGVHD; 14.3% vs. 32.8%, P = 0.029), but similar grade III-IV aGVHD (10.2% vs. 12.5%, P = 0.774), graft failure (GF) (15.1% vs. 15.5%, P = 0.658) and 5-year overall survival (90.6% vs. 83.7%, P = 0.251). As a source of stem cell, peripheral blood stem cells (PBSC) resulted in less GF (18% vs. 9.1% P = 0.013), similar grade II-IV aGVHD (28.1% vs. 17.4%, P = 0.258), chronic GVHD (25.8% vs. 29.3%, P = 0.822) and similar outcomes (89.7% vs. 82.4%, P =0.665) when compared to bone marrow (BM). In univariate analysis, GF (P < 0.001) and grade II-IV aGVHD (P = 0.009) were predictors of poor survival. In multivariate analysis, only GF was associated with poor survival (P = 0.012). The outcome of AD and PBSC HSCT were comparable to that of MSD and BM HSCT in the Asia Pacific region.