Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: <0.1%, I-B: 0.1–10%, I-C: >10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15<10% and day-33<0.01%, II-B: day-15≥10% or day-33≥0.01% but not both, II-C: day-15≥10% and day-33≥0.01%), which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD≥10−4 were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients’ prognosis, with 20–35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥10−4. We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.

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Background and aim:We reviewed the results and pattern of failure of the consensus HB/HCC 1996 treatment protocol for pediatric hepatoblastoma (HB) in Hong Kong. The role of SIOPEL and Children's Hepatic tumors International Collaboration (CHIC) risk stratification was evaluated. Methods:Patients enrolled on the protocol from 1996 to 2014 were included. PRETEXT staging, SIOPEL, and CHIC risk groups were retrospectively assigned.Results: Sixty patients were enrolled with median age at diagnosis of 1.1 years and median followup time of 6.8 years. Alpha-fetoprotein (AFP) was raised (>100 ng/mL) in 58 (97%) patients.Five (8%) had metastases at presentation and 7 (12%) experienced tumor rupture prior to or during treatment. Twenty-nine patients (48%) received a first-line cisplatin, 5-fluorouracil, and vincristine regimen only while 23 (38%) also had alternative chemotherapeutic agents. Hepatic resection could be performed in 48 (80%) patients. Three (5%) patients underwent upfront liver transplantation. Five-year event-free survival and overall survival rates were 69.2% ± 6.1% and 77.6% ± 5.5% respectively. Among the 16 patients with relapse/progression, 9 had intrahepatic failure only, 5 had distant failure only, and 2 had combined local and distant failure. Predictors of inferior outcome included advanced Evans staging, disease involving both lobes, rupture, low AFP, and suboptimal response to first-line chemotherapy. Assigned in 44 patients, PRETEXT staging, SIOPEL, and CHIC risk groups significantly predicted EFS and OS. Conclusions:Although the consensus HB/HCC 1996 protocol led to cure in three-quarters of pediatric HB patients, an upfront risk stratification system is required to identify and improve the outcome of high-risk patients. K E Y W O R D Shepatoblastoma, pediatric, pretreatment extent of disease, relapse, risk stratification

A fetus of Chinese descent presented with ultrasound features of anemia at 20 weeks' gestation. Father had low a mean corpuscular volume (MCV) level. Multiplex gap-polymerase chain reaction (gap-PCR) excluded common α-thalassemia (α-thal) deletions and mutations and PCR sequencing of the α1- and α2-globin genes were negative. The fetus had a normal karyotype. Array comparative genomic hybridization (aCGH) showed a single copy loss of 189.87 kb in chromosome 11p15.4, involving the whole β-globin gene cluster, inherited from the father. Multiplex ligation-dependent probe amplification (MLPA) confirmed the deletion included the ε-globin gene, confirming the diagnosis of heterozygous (εγδβ)-thalassemia [(εγδβ)-thal], also inherited from the father. The fetus had a worsening anemic condition in utero and required a transfusion at 26 weeks' gestation, raising the hemoglobin (Hb) level from 5.3 to 12.6g/dL. A cesarean-section was subsequently performed at 32 weeks' gestation because of reduced fetal movements, and a 1650g baby girl with good Apgar scores was delivered. Hemoglobin at birth was 12.8g/dL, gradually dropping to 6.8 g/dL, requiring three neonatal transfusions. Her condition gradually stabilized after 2 months with Hb stable at 8.0 g/dL. Family screening by MLPA showed that the paternal grandmother carried the same deletion. The deletion in this case is distinct and is the reported first case. The deletion transmitted across three successive generations with great phenotypic variation. The final adult phenotype of (εγδβ)-thal is usually mild, therefore, with accurate prenatal diagnosis this condition is salvageable by in utero and early neonatal transfusions, preventing adverse pregnancy and neonatal outcomes.