Management of acute intra-abdominal hemorrhage in ruptured hepatoblastoma with transarterial embolization using calibrated gelfoam particles.

This brief report aims to evaluate the treatment outcome of transarterial embolization in ruptured hepatoblastoma complicated with acute intra-abdominal hemorrhage. Three children (mean age 6 years) with high-risk hepatoblastoma presented with rupture and acute intra-abdominal hemorrhage. In addition to aggressive fluid resuscitation and blood product support, super-selective embolization of the arteries with active bleeding or pseudoaneurysm was performed using calibrated gelfoam particles, with a technical success rate of 100%. Hemodynamic status and hemoglobin level were normalized in all patients within 2 days postembolization. The 30-day survival rate was 100%. No major complication was detected apart from mild elevation of alanine transaminase.

Epidemiology and outcomes of pediatric transplant-associated thrombotic microangiopathy in Hong Kong.

BACKGROUND: Transplant-associated thrombotic microangiopathy (TA-TMA) is an under-recognized yet potentially devastating complication of hematopoietic stem cell transplantation (HSCT) which had increased awareness in recent years. This report summarizes the demographics and outcomes of pediatric TA-TMA in Hong Kong. METHODS: All patients aged below 18 years who underwent HSCT in the Hong Kong Children's Hospital and were diagnosed to have TA-TMA during the 2-year period from April 1, 2019 to March 31, 2021 were included. RESULTS: A total of 73 transplants (51 allogeneic and 22 autologous) in 63 patients had been performed. Six patients (four males and two females) developed TA-TMA at a median duration of 2.5 months post-HSCT. The incidence rate was 9.52%. Of the six TA-TMA patients, five underwent allogenic one underwent autologous HSCT, respectively. Three of them were histologically proven. All four patients with cyclosporine had stopped the drug once TA-TMA was suspected. Median six doses of eculizumab were administered to five out of six patients. Three patients died (two due to fungal infection and one due to acute-on-chronic renal failure) within 3 months upon diagnosis of TA-TMA. Among three survivors, two stabilized with mild stage 2 chronic kidney disease (CKD) while the other suffered from stage 5 end-stage CKD requiring lifelong dialysis. CONCLUSION: In conclusion, recognition and diagnosis of TA-TMA are challenging. Early recognition and prompt administration of complement blockage with eculizumab may be beneficial in selected cases. Further prospective research studies are recommended to improve the management and outcomes of TA-TMA.

Reactivation of Epstein-Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function.

Epstein-Barr nuclear antigen 1 (EBNA1) plays a vital role in the maintenance of the viral genome and is the only viral protein expressed in nearly all forms of Epstein-Barr virus (EBV) latency and EBV-associated diseases, including numerous cancer types. To our knowledge, no specific agent against EBV genes or proteins has been established to target EBV lytic reactivation. Here we report an EBNA1- and Zn2+-responsive probe (ZRL5P4) which alone could reactivate the EBV lytic cycle through specific disruption of EBNA1. We have utilized the Zn2+ chelator to further interfere with the higher order of EBNA1 self-association. The bioprobe ZRL5P4 can respond independently to its interactions with Zn2+ and EBNA1 with different fluorescence changes. It can selectively enter the nuclei of EBV-positive cells and disrupt the oligomerization and oriP-enhanced transactivation of EBNA1. ZRL5P4 can also specifically enhance Dicer1 and PML expression, molecular events which had been reported to occur after the depletion of EBNA1 expression. Importantly, we found that treatment with ZRL5P4 alone could reactivate EBV lytic induction by expressing the early and late EBV lytic genes/proteins. Lytic induction is likely mediated by disruption of EBNA1 oligomerization and the subsequent change of Dicer1 expression. Our probe ZRL5P4 is an EBV protein-specific agent that potently reactivates EBV from latency, leading to the shrinkage of EBV-positive tumors, and our study also suggests the association of EBNA1 oligomerization with the maintenance of EBV latency.

Neurological complications in Chinese children undergoing hematopoietic stem cell transplantation.

BACKGROUND: Hematopoietic stem cell transplantation, despite being a curative treatment for various pediatric disorders, is associated with significant acute and chronic complications. METHODS: This retrospective review of 196 hematopoietic stem cell transplantation episodes (144 allogeneic, 52 autologous) performed in a tertiary pediatric unit focused on neurological symptoms and complications occurred from the start of conditioning to within 3 years of transplantation. Indications for transplantation included both benign and malignant diseases. For episodes involving allogeneic transplantation, 42% of donors were matched-unrelated, 19% were matched-sibling, and 12% were haploidentical.  RESULTS: Neurological complications developed in 17% of all hematopoietic stem cell transplantation episodes. Tumors of central nervous system and leukemia or lymphoma were two indications reported to have higher incidence of 42% and 21%, respectively. The occurrence of neurological complications was significantly associated with primary diagnosis (p = 0.01), central nervous system involvement by underlying disease (p = 0.001), and radiation-based conditioning (p = 0.018). Upon multivariate analysis, central nervous system involvement by underlying disease remained to be the only significant factor (p = 0.019), while radiation-based containing conditioning (p = 0.029) is revealed to be associated when considering allogeneic transplantation alone. Pre-transplant central nervous system-directed treatment, allogeneic versus autologous donor, stem cell source, donor type, busulfan use, and cyclosporin use were not significantly associated with neurological complications. Patients with neurological complications were also found to have an inferior 2-year overall survival (53.9% ± 8.8% versus 63.8% ± 4.2%; p = 0.016). CONCLUSION: Neurological complications were common in pediatric hematopoietic stem cell transplantation and were associated with adverse outcome; non-radiation containing conditioning regimens might be beneficial in mitigating the risk of such complications.

High risk Epstein-Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma.

Whether certain variants of Epstein-Barr virus (EBV) are linked to the pathogenesis of nasopharyngeal carcinoma (NPC), which shows a marked geographic restriction, remains an unresolved issue. We performed a case-control study comparing genomic sequences of EBV isolated from saliva samples of 142 population carriers with those from primary tumour biopsies derived from 62 patients with NPC of Hong Kong. Cluster analysis discovered five EBV subgroups 1A-C and 2A-B amongst the population carriers in contrast to the predominance of 1A and -B in the majority of NPC. Genome-wide association study (GWAS) identified a panel of NPC-associated single nucleotide polymorphisms (SNPs) and indels in the EBER locus. The most significant polymorphism, which can be found in 96.8% NPC cases and 40.1% population carriers of Hong Kong, is a four-base-deletion polymorphism downstream of EBER2 (EBER-del) from coordinates 7188-7191 (p = 1.91 × 10-7 ). In addition, the predicted secondary structure of EBER2 is altered with likely functional consequence in nearly all NPC cases. Using the SNPs and indels associated with NPC, genetic risk score is assigned for each EBV variant. EBV variants with high genetic risk score are found to be much more prevalent in Hong Kong Chinese than individuals of other geographic regions and in NPC than other EBV-associated cancers. We conclude that high risk EBV variants with polymorphisms in the EBER locus, designated as HKNPC-EBERvar, are strongly associated with NPC. Further investigation of the biological function and potential clinical application of these newly identified polymorphisms in NPC and other EBV-associated cancers is warranted.

Whole-exome sequencing identifies MST1R as a genetic susceptibility gene in nasopharyngeal carcinoma.

Multiple factors, including host genetics, environmental factors, and Epstein-Barr virus (EBV) infection, contribute to nasopharyngeal carcinoma (NPC) development. To identify genetic susceptibility genes for NPC, a whole-exome sequencing (WES) study was performed in 161 NPC cases and 895 controls of Southern Chinese descent. The gene-based burden test discovered an association between macrophage-stimulating 1 receptor (MST1R) and NPC. We identified 13 independent cases carrying the MST1R pathogenic heterozygous germ-line variants, and 53.8% of these cases were diagnosed with NPC aged at or even younger than 20 y, indicating that MST1R germline variants are relevant to disease early-age onset (EAO) (age of ≤20 y). In total, five MST1R missense variants were found in EAO cases but were rare in controls (EAO vs. control, 17.9% vs. 1.2%, P = 7.94 × 10(-12)). The validation study, including 2,160 cases and 2,433 controls, showed that the MST1R variant c.G917A:p.R306H is highly associated with NPC (odds ratio of 9.0). MST1R is predominantly expressed in the tissue-resident macrophages and is critical for innate immunity that protects organs from tissue damage and inflammation. Importantly, MST1R expression is detected in the ciliated epithelial cells in normal nasopharyngeal mucosa and plays a role in the cilia motility important for host defense. Although no somatic mutation of MST1R was identified in the sporadic NPC tumors, copy number alterations and promoter hypermethylation at MST1R were often observed. Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of the MST1R-mediated signaling pathways.

An update on genomic-guided therapies for pediatric solid tumors.

Currently, out of the 82 US FDA-approved targeted therapies for adult cancer treatments, only three are approved for use in children irrespective of their genomic status. Apart from leukemia, only a handful of genomic-based trials involving children with solid tumors are ongoing. Emerging genomic data for pediatric solid tumors may facilitate the development of precision medicine in pediatric patients. Here, we provide an up-to-date review of all reported genomic aberrations in the eight most common pediatric solid tumors with whole-exome sequencing or whole-genome sequencing data (from cBioPortal database, Pediatric Cancer Genome Project, Therapeutically Applicable Research to Generate Effective Treatments) and additional non-whole-exome sequencing studies. Potential druggable events are highlighted and discussed so as to facilitate preclinical and clinical research in this area.

Congenital intestinal fibrosarcoma with rapid recurrence requiring adjuvant chemotherapy.

A total of 16 cases of congenital fibrosarcoma have been reported from 1975 to March 2015. Five of the 16 had abnormal fusion between erythroblast transformation specific translocation variant 6 and neurotrophin recptor gene neurotrophic tyrosine kinase, receptor, type 3 (ETV6-NTRK3); in another five out of 16 this was absent, and six were not tested. All were managed by surgical resection but none involved metastasis. Herein we report the case of a newborn baby girl with congenital fibrosarcoma negative for ETV6-NTRK3 gene fusion, who presented with ileal perforation and positive resection margin. She had rapid recurrence with lymph node metastasis treated with postoperative chemotherapy. There was no further recurrence at >3 years of follow up.

Inhibition of class I histone deacetylases by romidepsin potently induces Epstein-Barr virus lytic cycle and mediates enhanced cell death with ganciclovir.

Pan-histone deacetylase (HDAC) inhibitors, which inhibit 11 HDAC isoforms, are widely used to induce Epstein-Barr virus (EBV) lytic cycle in EBV-associated cancers in vitro and in clinical trials. Here, we hypothesized that inhibition of one or several specific HDAC isoforms by selective HDAC inhibitors could potently induce EBV lytic cycle in EBV-associated malignancies such as nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). We found that inhibition of class I HDACs, particularly HDAC-1, -2 and -3, was sufficient to induce EBV lytic cycle in NPC and GC cells in vitro and in vivo. Among a panel of selective HDAC inhibitors, the FDA-approved HDAC inhibitor romidepsin was found to be the most potent lytic inducer, which could activate EBV lytic cycle at ∼0.5 to 5 nM (versus ∼800 nM achievable concentration in patients' plasma) in more than 75% of cells. Upregulation of p21(WAF1) , which is negatively regulated by class I HDACs, was observed before the induction of EBV lytic cycle. The upregulation of p21(WAF1) and induction of lytic cycle were abrogated by a specific inhibitor of PKC-δ but not the inhibitors of PI3K, MEK, p38 MAPK, JNK or ATM pathways. Interestingly, inhibition of HDAC-1, -2 and -3 by romidepsin or shRNA knockdown could confer susceptibility of EBV-positive epithelial cells to the treatment with ganciclovir (GCV). In conclusion, we demonstrated that inhibition of class I HDACs by romidepsin could potently induce EBV lytic cycle and mediate enhanced cell death with GCV, suggesting potential application of romidepsin for the treatment of EBV-associated cancers.

Role of ATM in the formation of the replication compartment during lytic replication of Epstein-Barr virus in nasopharyngeal epithelial cells.

UNLABELLED: Epstein-Barr virus (EBV), a type of oncogenic herpesvirus, is associated with human malignancies. Previous studies have shown that lytic reactivation of EBV in latently infected cells induces an ATM-dependent DNA damage response (DDR). The involvement of ATM activation has been implicated in inducing viral lytic gene transcription to promote lytic reactivation. Its contribution to the formation of a replication compartment during lytic reactivation of EBV remains poorly defined. In this study, the role of ATM in viral DNA replication was investigated in EBV-infected nasopharyngeal epithelial cells. We observed that induction of lytic infection of EBV triggers ATM activation and localization of DDR proteins at the viral replication compartments. Suppression of ATM activity using a small interfering RNA (siRNA) approach or a specific chemical inhibitor profoundly suppressed replication of EBV DNA and production of infectious virions in EBV-infected cells induced to undergo lytic reactivation. We further showed that phosphorylation of Sp1 at the serine-101 residue is essential in promoting the accretion of EBV replication proteins at the replication compartment, which is crucial for replication of viral DNA. Knockdown of Sp1 expression by siRNA effectively suppressed the replication of viral DNA and localization of EBV replication proteins to the replication compartments. Our study supports an important role of ATM activation in lytic reactivation of EBV in epithelial cells, and phosphorylation of Sp1 is an essential process downstream of ATM activation involved in the formation of viral replication compartments. Our study revealed an essential role of the ATM-dependent DDR pathway in lytic reactivation of EBV, suggesting a potential antiviral replication strategy using specific DDR inhibitors. IMPORTANCE: Epstein-Barr virus (EBV) is closely associated with human malignancies, including undifferentiated nasopharyngeal carcinoma (NPC), which has a high prevalence in southern China. EBV can establish either latent or lytic infection depending on the cellular context of infected host cells. Recent studies have highlighted the importance of the DNA damage response (DDR), a surveillance mechanism that evolves to maintain genome integrity, in regulating lytic EBV replication. However, the underlying molecular events are largely undefined. ATM is consistently activated in EBV-infected epithelial cells when they are induced to undergo lytic reactivation. Suppression of ATM inhibits replication of viral DNA. Furthermore, we observed that phosphorylation of Sp1 at the serine-101 residue, a downstream event of ATM activation, plays an essential role in the formation of viral replication compartments for replication of virus DNA. Our study provides new insights into the mechanism through which EBV utilizes the host cell machinery to promote replication of viral DNA upon lytic reactivation.

Autologous cord blood transplantation for metastatic neuroblastoma.

Auto-SCT is a common approach for metastatic neuroblastoma with the intention to rescue hematopoiesis after megadose chemotherapy. PBSC or BM is the usual stem cell source for auto-SCT. Auto-CBT for neuroblastoma has very rarely been performed. Currently, case reports are available for two patients only. We performed 13 auto-SCTs for high-risk neuroblastoma from 2007 to 2013, including four cases of metastatic neuroblastoma aged 11-64 months treated with auto-CBT. All four patients had partial or CR to upfront treatments before auto-CBT. Nucleated cell dose and CD34+ cell dose infused were 2.8-8.7 × 10(7) /kg and 0.36-3.9 × 10(5) /kg, respectively. Post-thawed viability was 57-76%. Neutrophil engraftment (>0.5 × 10(9) /L) occurred at 15-33 days, while platelet engraftment occurred at 31-43 days (>20 × 10(9) /L) and 33-65 days (>50 × 10(9) /L) post-transplant, respectively. There was no severe acute or chronic complication. Three patients survived for 1.9-7.7 yr without evidence of recurrence. One patient relapsed at 16 months post-transplant and died of progressive disease. Cord blood may be a feasible alternative stem cell source for auto-SCT in patients with stage 4 neuroblastoma, and outcomes may be improved compared to autologous PBSC or BM transplants.

11C-Acetate Positron Emission Tomography for Detection of Occult Metastatic Recurrence in Hepatoblastoma.

Hepatoblastoma is the most common primary liver cancer in the pediatric population. Disease relapse might be occult and difficult to detect. C-acetate positron emission tomography has been applied in patients with hepatocellular carcinoma due to the insensitivity of fluorodeoxyglucose, but data on hepatoblastoma patients have been scarce. We describe the use of C-acetate positron emission tomography/computed tomography scan as a sensitive method in the identification of an occult bony metastatic recurrence in a 6-year-old girl with a history of hepatoblastoma treated with chemotherapy.

Acute Leukemia in Down Syndrome Children in Hong Kong: Retrospective Review.

BACKGROUND: Children with Down syndrome (DS) are at higher risk of developing acute leukemia. Treatment continues to evolve as we accumulate better understanding of the distinctive clinical and biological features of acute leukemia in DS patients. PROCEDURE: A retrospective review of the clinical features, treatment outcomes, and survival of DS children with acute leukemia in Hong Kong from 1993 to 2013 was conducted. Patients were identified from the registry of the Hong Kong Pediatric Hematology and Oncology study group. RESULTS: This cohort included a total of 29 patients with DS. Ten were diagnosed with acute lymphoblastic leukemia and 19 had acute myeloid leukemia (AML). The mean follow-up duration was 8.3 years (range, 0.6 mo to 18.1 y). The 5-year overall survival and event-free survival for DS-acute lymphoblastic leukemia and DS-AML were 65.6%, 54.9%, 89.5%, and 89.5%, respectively. CONCLUSIONS: The clinical characteristics and treatment outcomes of DS patients with acute leukemia in Hong Kong were comparable with results from other international study groups. Patients with DS-AML had a better prognosis.

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.

Central diabetes insipidus: an unusual complication in a child with juvenile myelomonocytic leukemia and monosomy 7.

Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is unusual in pediatric patients with myeloid malignancies. We report here this rare complication in a child with neurofibromatosis type 1 who developed juvenile myelomonocytic leukemia and monosomy 7. Our case and previously reported cases of DI arising as a complication in myeloid malignancies demonstrate a close association with deletion of chromosome 7. The clinical characteristics and outcomes of these uncommon cases in children are reviewed and discussed.

Contribution of Epstein-Barr Virus Lytic Proteins to Cancer Hallmarks and Implications from Other Oncoviruses.

Epstein-Barr virus (EBV) is a prevalent human gamma-herpesvirus that infects the majority of the adult population worldwide and is associated with several lymphoid and epithelial malignancies. EBV displays a biphasic life cycle, namely, latent and lytic replication cycles, expressing a diversity of viral proteins. Among the EBV proteins being expressed during both latent and lytic cycles, the oncogenic roles of EBV lytic proteins are largely uncharacterized. In this review, the established contributions of EBV lytic proteins in tumorigenesis are summarized according to the cancer hallmarks displayed. We further postulate the oncogenic properties of several EBV lytic proteins by comparing the evolutionary conserved oncogenic mechanisms in other herpesviruses and oncoviruses.

The incidence, risk factors, and outcomes of symptomatic avascular necrosis of bone among Chinese pediatric patients with acute lymphoblastic leukemia.

BACKGROUND: Avascular necrosis (AVN) of bone is a debilitating complication of pediatric patients with acute lymphoblastic leukemia (ALL). While it is extensively studied and reported in Western population, studies focused on Orientals are limited. This study aims to evaluate the incidence, risk factors, and clinical outcomes of AVN among Chinese children with ALL. METHODS: This study is a retrospective, territory-wide population-based cohort study of pediatric patients with ALL enrolled on one of the three consecutive ALL study protocols (ALL-IC-BFM 2002, CCLG-ALL 2008, and CCCG-ALL 2015). RESULTS: A total of 24 out of 533 pediatric subjects with ALL (4.5%) had symptomatic AVN. Age was the single most important risk factor associated with the development of AVN. Only three patients were below age of 10 at the time of diagnosis of ALL. The incidences of AVN in patients aged above and below 10 years were 18.2% ± 3.6% and 0.8% ± 0.5%, respectively, and were significantly different (p < 0.005). Treatment protocol, immunophenotype, and gender were not predictive of AVN. Among the 24 patients, five required orthopedic interventions in view of progressive and severe disease. For subjects with hip joints involvement, follow-up assessments showed 12 of 22 hip joints had radiological progression over a median duration of 3.63 years. Seventeen of them did not have pain at the latest follow-up and among patients with pain (n = 7), five did not experience any limitation on activities of daily living while two required use of walking aids or wheelchair. CONCLUSION: The incidence of symptomatic AVN in Chinese ALL patients was comparable to other studies in Western population. Adolescent age more than 10 years old was recognized to be the most important factor for development of AVN. Significant proportion of patients had radiological progression over time with a small percentage of subjects had daily activities affected.

Norovirus infection in pediatric hematopoietic stem cell transplantation recipients: incidence, risk factors, and outcome.

Norovirus infections are increasingly being recognized as important causes of diarrhea in hematopoietic stem cell transplantation (HSCT) recipients. This retrospective study aimed to evaluate the cumulative incidence, risk factors, and outcomes of norovirus infection in pediatric HSCT recipients. Among 55 patients age <21 years who underwent first HSCT between July 2007 and June 2011, 49 patients developed diarrhea and had stool tested for norovirus. Eight of these patients were found to be infected with norovirus. All were sporadic cases and manifested with nausea, vomiting, and diarrhea. The median age of these patients was 5.2 years (range, 0.5-18.5 years). Six were males. Seven patients underwent unrelated donor HSCT, and 1 patient underwent autologous cord blood HSCT. Two patients had norovirus infection before HSCT that persisted after transplantation. In the remaining 6 patients, norovirus developed at a median of 36.5 days posttransplantation (range, 5-517 days). The cumulative incidence of norovirus infection was 12.9% at 2 years posttransplantation. Risk factors for norovirus infection included the use of peripheral blood or cord blood as the stem cell source (P = .043) and administration of fludarabine (P = .002) and alemtuzumab (P = .011). The median time to viral clearance was 145 days (range, 13-263 days). Four-year survival was similar in norovirus-infected patients and noninfected patients (56.3% versus 58.3%).

Prognosis and outcome of relapsed acute lymphoblastic leukemia: a Hong Kong Pediatric Hematology and Oncology Study Group report.

BACKGROUND: In 2000, the Hong Kong Pediatric Hematology Oncology Study Group started a new relapsed acute lymphoblastic leukemia (ALL) treatment protocol based on modified ALL-REZ BFM 96 protocol aiming at improving the treatment outcome in Chinese children. PROCEDURE: All patients in Hong Kong with first relapse of childhood ALL were included. Patients were stratified into four risk groups (S1, S2, S3, and S4) and the treatment consisted of intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation, if indicated. RESULTS: Fifty-six patients were recruited and median age at diagnosis of ALL was 4.6 (range, 0.3-17) years. The median time from initial diagnosis to relapse was 2.5 (range, 0.3-9.1) years and follow-up time was 2.7 (range, 0-9.9) years. Forty-nine patients (87.5%) achieved second complete remission (CR2). CR2 rates for S1, S2, S3, and S4 groups were 100%, 93%, 90%, and 67%, respectively. Five-year overall survival (OS) was 50.5 ± 6.9% and event-free survival (EFS) was 41.5 ± 7.1%. There was no significant difference in survival among S1, S2, and S3 groups but S4 patients performed significantly worse with 5-year OS and EFS of 8% and 0%, respectively. CONCLUSION: Children with relapsed ALL of S1-S3 risk groups could be successfully treated with intensified treatment protocol. The S4 high risk group needs more innovative approach to improve treatment outcome.

Infliximab for steroid refractory or dependent gastrointestinal acute graft-versus-host disease in children after allogeneic hematopoietic stem cell transplantation.

aGVHD of the GI tract is common after allogeneic HSCT. Corticosteroids are the mainstay of treatment. Recent data suggest infliximab might be beneficial for steroid refractory aGVHD. We reviewed our experience in 10 pediatric patients who developed severe steroid refractory aGVHD (stage 3, n = 6; stage 4, n = 4), after an allogeneic matched unrelated HSCT for various hematological diseases (leukemia, n = 7; thalassemia, n = 3). The median age was 9.5 yr (range, 0.8-18.5 yr). All patients received 10 mg/kg infliximab weekly for 3-4 doses. Eight patients had CR and two had partial response. None of the patients developed therapy-related adverse effects. All patients developed infections subsequently, which may or may not be related to infliximab. Five patients developed chronic GVHD (cGVHD) (four severe, one mild). Six patients died at 66-1451 days post-transplant, from infection (n = 3), aGVHD (n = 1), lung cGVHD (n = 1), or idiopathic pneumonia (n = 1). Four patients were alive at 238-924 days post-transplant, all of whom had an increase in BMI by six months post-transplant. In conclusion, infliximab is well tolerated and appears effective in children with steroid refractory or dependent GI aGVHD. Infection is common and mortality remains high.