Publications by authors named "Chi-Kong Li"

175 Publications

Effects of immersive virtual reality for preventing and managing anxiety, nausea and vomiting among paediatric cancer patients receiving their first chemotherapy: A study protocol for an exploratory trial.

PLoS One 2021 14;16(10):e0258514. Epub 2021 Oct 14.

The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Background: Anxiety, nausea and vomiting are common side effects suffered by paediatric patients receiving chemotherapy. Emerging evidence supports the efficacy of immersive virtual reality (IVR) on improving anxiety and distress symptoms including nausea and vomiting among this vulnerable group. This trial aims to assess the feasibility and acceptability of IVR for preventing and managing anxiety, nausea and vomiting among paediatric cancer patients receiving their first chemotherapy.

Method And Analysis: An exploratory trial supplemented by qualitative methods will be conducted. We will recruit 20 paediatric patients who are aged between 6 and 12 years, chemotherapy naïve, scheduled to receive their first intravenous chemotherapy and able to understand Chinese. Participants will be randomly allocated to intervention or control groups. The intervention group will receive the IVR intervention for three sessions as follows: 4 hours before chemotherapy, 5 minutes before and during their first course chemotherapy and 5 minutes before and during their second course chemotherapy. The control group will receive standard care only. Main outcome measures included (1) key parameters for the design of a definitive trial (i.e. screening, eligibility, consent and withdrawal rates); (2) anxiety, anticipatory and acute chemotherapy-induced nausea and vomiting for collection of preliminary data; (3) feasibility and acceptability of the intervention. Semi-structured interviews will be conducted with patients, parents and oncology nurses. Generalized estimating equations model will be used to compare each of the outcome measures across the time points between the two groups. Qualitative data will be analysed by conventional content analysis.

Expected Results: The results of this exploratory trial will inform the design and conduct of future definitive trial.

Trial Registration Number: ChiCTR1900021694; Pre-results.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258514PLOS
October 2021

Perceptions of Infertility Risk Among Chinese Parents of Children with Cancer: A Qualitative Study.

J Adolesc Young Adult Oncol 2021 Oct 5. Epub 2021 Oct 5.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, China.

Anticancer treatment may be associated with damage to the reproductive organs and risk of infertility in children with cancer. The collectivist cultural norms of Asian societies may lead Chinese parents to have unique concerns regarding infertility. This qualitative study explored the perceptions of infertility risk and parenthood among parents of childhood cancer survivors in Hong Kong. Thirteen parents were recruited via a snowball sampling approach from a nongovernmental organization in Hong Kong, representing nine survivors of childhood cancer (leukemia  = 5, solid tumors  = 4). The in-depth semistructured interviews were audiotaped and transcribed verbatim. A thematic analysis was performed using ATLAS.ti 8. Parents mostly perceived their children's fertility status as a distant concern ( = 11, 85%) but emphasized the need for timely information from clinicians when their children reach young adulthood ( = 8, 62%). They reported receiving inconsistent fertility information from different oncology practitioners ( = 9, 69%). A few parents acknowledged that under the influence of the Chinese culture, their children, especially sons, have an important duty to continue the family lineage. However, even if the cancer treatment were associated with infertility risk, almost all parents ( = 12, 92%) stated that it would still not affect their willingness to let their child undergo treatment because survival and cure were still their highest priority. Our findings suggest the need to proactively provide fertility information to parents both during active treatment and when survivors reach reproductive age. Future studies should evaluate the benefits of developing culturally relevant decision-making aids to address parents' informational needs regarding fertility issues.
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http://dx.doi.org/10.1089/jayao.2021.0106DOI Listing
October 2021

Functional Outcomes and Social Attainment in Asian/Pacific Islander Childhood Cancer Survivors in the United States: A Report from the Childhood Cancer Survivor Study.

Cancer Epidemiol Biomarkers Prev 2021 Oct 4. Epub 2021 Oct 4.

School of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong

Background: Given the relatively small population of Asians or Pacific Islanders (API) in the United States, studies describing long-term outcomes in API survivors of childhood cancer are limited. This study compared functional outcomes between API versus non-Hispanic White (NHW) survivors.

Methods: This study included 203 API five-year survivors (age at follow-up: 29.2 [SD=6.3] years) and 12,186 NHW survivors (age at follow-up 31.5[SD=7.3] years) from the Childhood Cancer Survivor Study. Self-reported functional outcomes of neurocognitive function, emotional distress, quality of life, and social attainment were compared between the two groups using multivariable regression, adjusted for sex, age at diagnosis and evaluation, cancer diagnosis, and neurotoxic treatment.

Results: No statistically significant race/ethnicity-based differences were identified in neurocognitive and emotional measures. API survivors reported, on average, less bodily pain than NHW survivors (mean 54.11 [SD=8.98] vs. 51.32 [SD=10.12]; P<.001). NHW survivors were less likely to have attained at least a college degree than API survivors (odds ratio[OR]=0.50; 95% confidence interval[CI]=0.34, 0.73). API survivors were more likely than NHW survivors to be never-married (OR=2.83, 95% CI=1.93, 4.13) and to live dependently (OR=3.10; 95% CI=2.02, 4.74). Older age (>45 years), brain tumor diagnosis, and higher cranial radiation dose were associated with poorer functional outcomes in API survivors (all, P's<0.05).

Conclusion: We observed differences in social attainment between API and NHW survivors, though statistically significant differences in neurocognitive and emotional outcomes were not identified.

Impact: Future studies should evaluate whether racial/ethnic differences in environmental and sociocultural factors may have differential effects on health and functional outcomes.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0628DOI Listing
October 2021

R4 RGS proteins suppress engraftment of human hematopoietic stem/progenitor cells by modulating SDF-1/CXCR4 signaling.

Blood Adv 2021 Sep 9. Epub 2021 Sep 9.

The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM) microenvironment are tightly regulated by the chemokine SDF-1 and its G-protein-coupled receptor CXCR4, which on engagement with G-protein subunits, trigger downstream migratory signals. Regulators of G-protein signaling (RGS) are GTPase-accelerating protein of the Gα subunit and R4 subfamily members have been implicated in SDF-1-directed trafficking of mature hematopoietic cells, yet their expression and influence on HSPCs remain mostly unknown. Here, we demonstrated that human CD34+ cells expressed multiple R4 RGS genes, of which RGS1, RGS2, RGS13,and RGS16 were significantly upregulated by SDF-1 in a CXCR4-dependent fashion. Forced overexpression of RGS1, RGS13, or RGS16 in CD34+ cellsnot only inhibited SDF-1-directed migration, calcium mobilization, and phosphorylation of AKT, ERK, and STAT3 in vitro, but also markedly reduced BM engraftment in transplanted NOD/SCID mice. Genome-wide microarray analysis of RGS-overexpressing CD34+ cells detected downregulation of multiple effectors with established roles in stem cell trafficking/maintenance. Convincingly, gain-of-function of selected effectors or ex vivo priming with their ligands significantly enhanced HSPC engraftment. We also constructed an evidence-based network illustrating the overlapping mechanisms of RGS1, RGS13 and RGS16 downstream of SDF-1/CXCR4 and Gαi. This model shows that these RGS members mediate compromised kinase signaling and negative regulation of stem cell functions, complement activation, proteolysis and cell migration. Collectively, this study uncovers an essential inhibitory role of specific R4 RGS proteins in stem cell engraftment, which could potentially be exploited to develop improved clinical HSPC transplantation protocols.
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http://dx.doi.org/10.1182/bloodadvances.2020003307DOI Listing
September 2021

Technology Acceptance Among Patients With Hemophilia in Hong Kong and Their Expectations of a Mobile Health App to Promote Self-management: Survey Study.

JMIR Form Res 2021 Sep 9;5(9):e27985. Epub 2021 Sep 9.

Department of Pediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong.

Background: The lifelong management of hemophilia is demanding and complex. In July 2019, we published a review in the Journal of Medical Internet Research, summarizing telehealth interventions that facilitate monitoring of bleeding events and promoting the appropriate use of clotting factors among patients with hemophilia. This work has led to the development of a community program that aims to harness technology to promote self-management among patients with hemophilia in Hong Kong.

Objective: Before the inception of this program, we conducted a cross-sectional survey to evaluate the patients' level of technology acceptance and identify their expectations of the use of mobile technology for self-management of hemophilia.

Methods: In total, 56 participants (75% adult patients and 25% parents of pediatric patients; 87.5% with moderate to severe disease) were recruited from a local nongovernmental organization that serves patients with hemophilia. They rated their perceived confidence and acceptance in using the new mobile technology (score 1 to 5 for each item, with a higher score indicating better acceptance) using a structured questionnaire (adapted from the Technology Acceptance Model). They also identified the top features that they perceived to be the most important components of a mobile app for the self-management of hemophilia. The Mann-Whitney U test was used to compare technology acceptance scores across subgroups of different clinical and socioeconomic characteristics.

Results: In general, the participants considered themselves skilled in using mobile apps (mean 4.3, 95% CI 4.1-4.5). They were willing to learn to use the new mobile app to organize their bleeding records (mean 4.0, 95% CI 3.7-4.3) and to manage their health (mean 4.2, 95% CI 4.1-4.5). Participants who lived in public housing (a surrogate marker for lower socioeconomic status in Hong Kong) reported lower technology acceptance than those who lived in private housing (P=.04). The most important features identified by the participants concerned documenting of infusion logs (n=49, 87.5%), bleeding events (n=48, 85.7%), and the secure delivery of the bleeding information to health care professionals (n=40, 71.4%).

Conclusions: It is encouraging to infer that patients with hemophilia in Hong Kong are receptive to the use of mobile health technology. The findings of this survey are applicable in designing the key features of a patient-centered, multimodal program harnessing mobile technology to promote self-management among patients with hemophilia. Future studies should evaluate participants' acceptability and perceived usability of the mobile app via user metrics and assess clinical and humanistic outcomes of this program.
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http://dx.doi.org/10.2196/27985DOI Listing
September 2021

Transition from Acute Treatment to Survivorship: Exploring the Psychosocial Adjustments of Chinese Parents of Children with Cancer or Hematological Disorders.

Int J Environ Res Public Health 2021 07 23;18(15). Epub 2021 Jul 23.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.

Objectives: Parents of children diagnosed with critical illnesses face multiple challenges during their caregiving experience. However, relevant studies have been limited in the Chinese context. Guided by the stress and coping model, we conducted a qualitative study to identify the stressors, coping strategies, and adjustment experiences of Hong Kong parents of children with cancer or hematological disorders.

Methods: We recruited 15 parents of children with cancer or hematological disorders requiring bone marrow transplantation and were currently >2 years post-treatment. They participated in a 30-min semi-structured interview. Thematic analysis was performed using the grounded theory approach.

Results: The stressors reported by parents included a high caregiving burden during their children's diagnosis and treatment stages. The fear of recurrence, the need for information, and concerns about late effects were also common among the parents during their children's transition/survivorship stage. To cope with these stressors, the parents commonly used problem-focused (e.g., seeking help from professionals and support groups) and emotion-focused (e.g., behavioral distractions, venting, and crying) strategies. Despite these stressors, parents reported positive changes through the caregiving experience, such as improved family relationships, developing health-protective habits, and the reprioritization of different aspects of life.

Conclusions: Parents encounter different stressors during the cancer care continuum. Using different coping strategies, parents experience positive changes amidst caregiving. Future studies should explore culturally relevant adaptive coping strategies to enhance parents' psychosocial adjustment.
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http://dx.doi.org/10.3390/ijerph18157815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345777PMC
July 2021

Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial.

Lancet Oncol 2021 09 27;22(9):1322-1332. Epub 2021 Jul 27.

Department of Hematology/Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China.

Background: Vincristine plus dexamethasone pulses are generally used throughout maintenance treatment for childhood acute lymphoblastic leukaemia. However, previous studies remain inconclusive about the benefit of this maintenance therapy and the absence of randomised, controlled trials in patients with low-risk or high-risk acute lymphoblastic leukaemia provides uncertainty. We therefore aimed to determine if this therapy could be safely omitted beyond 1 year of treatment without leading to an inferior outcome in any risk subgroup of childhood acute lymphoblastic leukaemia.

Methods: This open-label, multicentre, randomised, phase 3, non-inferiority trial involved 20 major medical centres across China. We enrolled patients who were aged 0-18 years with newly diagnosed acute lymphoblastic leukaemia that was subsequently in continuous remission for 1 year after initial treatment. Patients with secondary malignancy or primary immunodeficiency were excluded. Eligible patients were classified as having low-risk, intermediate-risk, or high-risk acute lymphoblastic leukaemia based on minimal residual disease and immunophenotypic and genetic features of leukaemic cells. Randomisation and analyses were done separately for the low-risk and intermediate-to-high-risk cohorts. Randomisation was generated by the study biostatistician with a block size of six. Stratification factors included participating centre, sex, and age at diagnosis; the low-risk cohort was additionally stratified for ETV6-RUNX1 status, and the intermediate-to-high-risk cohort for cell lineage. Patients in each risk cohort were randomly assigned (1:1) to either receive (ie, the control group) or not receive (ie, the experimental group) seven pulses of intravenous vincristine (1·5 mg/m) plus oral dexamethasone (6 mg/m per day for 7 days) during the second year of treatment. The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate-to-high-risk cohorts, with a non-inferiority margin of 0·05 (5%). The analysis was by intention to treat. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-14005706.

Findings: Between Jan 1, 2015, and Feb 20, 2020, 6141 paediatric patients with newly diagnosed acute lymphoblastic leukaemia were registered to this study. Approximately 1 year after diagnosis and treatment, 5054 patients in continuous remission were randomly assigned, including 2923 (1442 in the control group and 1481 in the experimental group) with low-risk acute lymphoblastic leukaemia and 2131 (1071 control, 1060 experimental) with intermediate-to-high risk acute lymphoblastic leukaemia. Median follow-up for patients who were alive at the time of analysis was 3·7 years (IQR 2·8-4·7). Among patients with low-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (90·3% [95% CI 88·4-92·2] vs 90·2% [88·2-92·2]; p=0·90). The one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·024, establishing non-inferiority. Among patients with intermediate-to-high-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (82·8% [95% CI 80·0-85·7] vs 80·8% [77·7-84·0]; p=0·90), but the one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·055, giving a borderline inferior result for those in the experimental group. In the low-risk cohort, we found no differences in the rates of infections, symptomatic osteonecrosis, or other complications during the second year of maintenance treatment between patients in the control and experimental groups. Patients with intermediate-to-high-risk acute lymphoblastic leukaemia in the control group were more likely to develop grade 3-4 pneumonia (26 [2·4%] of 1071 vs ten [0·9%] of 1060) and vincristine-related peripheral neuropathy (17 [1·6%] vs six [0·6%]) compared with the experimental group. Incidence of grade 5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort (two [0·1%] of 1442 vs five [0·3%] of 1481) and intermediate-to-high risk cohort (six [0·6%] of 1071 vs five [0·5%] of 1060).

Interpretation: Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukaemia. Additional studies are needed for intermediate-to-high-risk acute lymphoblastic leukaemia.

Funding: VIVA China Children's Cancer Foundation, the National Natural Science Foundation of China, the China fourth round of Three-Year Public Health Action Plan (2015-2017), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00328-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416799PMC
September 2021

Therapeutics for paediatric oncological emergencies.

Drugs Context 2021 23;10. Epub 2021 Jun 23.

Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong.

Background: With advancements in the field of oncology, cancer survival rates have improved dramatically but modern cancer treatments also come with an increasing number of disease and treatment-associated complications. This article provides an updated narrative review on the pathophysiology, clinical presentations and latest management strategies for common paediatric oncological emergencies.

Methods: An extensive PubMed search of all human studies in the English literature was performed in Clinical Queries for different oncology syndromes and conditions using the following Medical Subject Headings: "tumour lysis syndrome", "hyperleukocytosis", "disseminated intravascular coagulation", "superior mediastinal syndrome", "superior vena cava syndrome", "sepsis", "severe inflammatory response syndrome", "acute respiratory distress syndrome", "posterior reversible encephalopathy syndrome" and "reversible posterior leukoencephalopathy syndrome". Categories were limited to clinical trials and reviews for ages from birth to 18 years.

Results: The general description, presentation and management of these oncologic emergencies are systematically described. Early recognition along with prompt and proactive treatment can reduce the chances of potential complications and improve the clinical outcomes, thereby improving not only survival rates in oncology patients but also their clinical outcomes and quality of life.

Conclusions: Oncologic emergencies are associated with significant mortality and morbidity. Healthcare professionals involved with the care of oncology patients must be vigilant of these emergencies.
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http://dx.doi.org/10.7573/dic.2020-11-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232653PMC
June 2021

Awareness of diagnosis, treatment and risk of late effects in Chinese survivors of childhood cancer in Hong Kong.

Health Expect 2021 Aug 8;24(4):1473-1486. Epub 2021 Jun 8.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Background: For survivors of childhood cancer, awareness of personal health risks is a critical component of long-term health management.

Objective: To evaluate the awareness of the diagnosis, treatment and risk of late effects among survivors of childhood cancer in Hong Kong.

Methods: Between June 2019 and March 2020, this cross-sectional study recruited 155 adult survivors (mean age = 26.9, standard deviation [SD] = 6.4 years) and 45 parents of paediatric survivors (mean age = 11.1, SD = 3.6 years) from a long-term follow-up clinic. At >10 years post-treatment (mean = 13.4, SD = 7.6 years), they completed a structured questionnaire to report their cancer-specific knowledge. Multiple linear regression analysis was conducted to identify clinical, socioeconomic and behavioural factors associated with poor awareness.

Results: The majority of participants accurately recalled their diagnoses (73.5%) and major treatment modalities (chemotherapy 92.4%, radiation 82.9% and surgery 88.2%). However, less than half (45%) of the participants recognized more than 25% of the total late effects for which they were at risk. The highest levels of awareness were reported for endocrine problems (49%), neurocognitive impairment (44%) and secondary cancers (43%), and the lowest for peripheral neuropathy (21%) and vision problems (23%). Compared with survivors of haematological malignancies, those of central nervous system (CNS) tumours (standardized estimate [B] = -9.33, 95% confidence interval [95% CI]: -13.41 to -5.26) and non-CNS solid tumours (B = -8.47, 95% CI: -12.39 to -4.94) had less knowledge about their diagnosis. Retaining medical records (P < .0001) and better medical information-seeking habits (P = .048) were associated with better awareness.

Conclusions: Survivors of childhood cancer in Hong Kong have deficient awareness of their personal health risks. They may benefit from the provision of a survivorship care plan and personalized education regarding treatment-related late effects.

Patient Contribution: Patients contributed in designing the study tools. Results were presented at a non-governmental organization.
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http://dx.doi.org/10.1111/hex.13288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369092PMC
August 2021

Use of complementary or alternative medicine and potential interactions with chronic medications among Chinese survivors of childhood cancer.

J Cancer Surviv 2021 May 14. Epub 2021 May 14.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Purpose: This study explored the pattern of complementary or alternative medicine (CAM) use among Chinese survivors of childhood cancer and identified potential drug-CAM interactions and factors predicting CAM use.

Methods: This cross-sectional study recruited 393 survivors of childhood cancer (male, 57.8%; mean age, 17.7 [SD = 7.3] years; mean years post-treatment, 8.8 [SD = 5.0]) from a public hospital in Hong Kong. Participants reported CAM and over-the-counter medications that they used in the past year. Prescription drug data were extracted from pharmacy dispensing records. Potential interactions between concurrent CAM and chronic medications were identified from well-established CAM-drug/herb-drug interaction databases. A multivariate logistic regression was performed to analyze associations of socio-demographic and clinical factors with CAM use.

Results: Half (n = 205/393, 52.2%) of the participants reported the use of CAM. The most popular CAMs were traditional Chinese medicine (n = 127/205, 62.0%) and natural products (n = 114/205, 55.3%). Among the 69 survivors (33.7%) concurrently using CAM and chronic medications, one-third (n = 21/69, 30.4%) were at risk of drug-CAM interactions that are of moderate significance. Adult survivors were more likely to use CAM than pediatric survivors (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.31-4.41). Brain tumor survivors were more likely than other solid tumor survivors to use non-oral therapies (OR, 2.70; 95% CI, 1.01-7.72).

Conclusions: The prevalence of CAM use among Chinese survivors of childhood cancer was high. A minority of survivors had a risk of clinically significant CAM-drug interactions. Future studies should focus on survivors' behavior and motivations for CAM use.

Implications For Cancer Survivors: As the concurrent use of CAM and chronic medications might result in interactions, healthcare providers should proactively identify such interactions and develop referral pathways to promote evidence-based integrative therapies for survivors.
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http://dx.doi.org/10.1007/s11764-021-01051-5DOI Listing
May 2021

Neurocognitive and Behavioral Outcomes of Chinese Survivors of Childhood Lymphoblastic Leukemia.

Front Oncol 2021 20;11:655669. Epub 2021 Apr 20.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.

Background: Increasing attention has been dedicated to investigate modifiable risk factors of late effects in survivors of childhood cancer. This study aims to evaluate neurocognitive and behavioral functioning in a relatively young cohort of survivors of childhood acute lymphoblastic leukemia (ALL) in Hong Kong, and to identify clinical and socio-environmental factors associated with these outcomes.

Methods: This analysis included 152 survivors of childhood ALL who were ≥5 years post-diagnosis (52% male, mean [SD] age 23.5[7.2] years at evaluation, 17.2[7.6] years post-diagnosis). Survivors completed performance-based neurocognitive tests, and reported their emotional and behavioral symptoms using the Child/Adult Behavior Checklist. Socio-environmental variables (living space, fatigue, physical activity, family functioning, and academic stress) were self-reported using validated questionnaires. Clinical variables and chronic health conditions were extracted from medical charts. Multivariable linear modeling was conducted to test identify factors associated with neurocognitive/behavioral outcomes, adjusting for current age, sex, age at diagnosis and cranial radiation. An exploratory mediation analysis was performed to examine the mediating effects of risk factors on neurocognitive and behavioral outcomes.

Results: As compared to population norms, a minority of survivors developed mild-moderate impairment in motor processing speed (36.2%), memory (9.2%) and attention measures (4.0%-10.5%). Survivors also reported attention problems (12.5%), sluggish cognitive tempo (23.7%) and internalizing (depressive, anxiety and somatic symptoms) problems (17.1%). A minority of survivors developed mild-moderate treatment-related chronic conditions (n=37, 24.3%). As compared to survivors without chronic conditions, survivors with chronic conditions had more executive dysfunction (B=5.09, standard error [SE]=2.05; =0.014) and reported more attention problems (B=5.73, SE=1.43; <0.0001). Fatigue and poor family functioning was associated with multiple measures of behavior problems (all <0.001). A lower level of physical activity was correlated with more self-reported symptoms of inattention (B= -1.12, SE=0.38, =0.004) and sluggish cognitive tempo (B=-1.22, SE=0.41, =0.003). Exploratory analysis showed that chronic health conditions were associated with behavioral measures through fatigue as the mediator.

Conclusion: The majority of young Chinese survivors of ALL had normal cognitive and behavioral function. Regular monitoring of behavioral function should be performed on survivors who develop treatment-related chronic conditions. Health behavior and socio-environment factors may be potentially modifiable risk factors associated with health outcomes in survivors.
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http://dx.doi.org/10.3389/fonc.2021.655669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093634PMC
April 2021

Clinical characteristics of tumor lysis syndrome in childhood acute lymphoblastic leukemia.

Sci Rep 2021 05 6;11(1):9656. Epub 2021 May 6.

Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China.

Tumor lysis syndrome (TLS) is a common and fatal complication of childhood hematologic malignancies, especially acute lymphoblastic leukemia (ALL). The clinical features, therapeutic regimens, and outcomes of TLS have not been comprehensively analyzed in Chinese children with ALL. A total of 5537 children with ALL were recruited from the Chinese Children's Cancer Group, including 79 diagnosed with TLS. The clinical characteristics, treatment regimens, and survival of TLS patients were analyzed. Age distribution of children with TLS was remarkably different from those without TLS. White blood cells (WBC) count ≥ 50 × 10/L was associated with a higher risk of TLS [odds ratio (OR) = 2.6, 95% CI = 1.6-4.5]. The incidence of T-ALL in TLS children was significantly higher than that in non-TLS controls (OR = 4.7, 95% CI = 2.6-8.8). Hyperphosphatemia and hypocalcemia were more common in TLS children with hyperleukocytosis (OR = 2.6, 95% CI = 1.0-6.9 and OR = 5.4, 95% CI = 2.0-14.2, respectively). Significant differences in levels of potassium (P = 0.004), calcium (P < 0.001), phosphorus (P < 0.001) and uric acid (P < 0.001) were observed between groups of TLS patients with and without increased creatinine. Laboratory analysis showed that older age was associated with a higher level of creatinine. Calcium level was notably lower in males. WBC count, lactate dehydrogenase, and creatinine levels were significantly higher in T-ALL subgroup, whereas procalcitonin level was higher in B-ALL children. Older age, infant, a higher level of WBC and T-ALL were risk factors TLS occurrence. Hyperleukocytosis has an impact on the severity of TLS, while renal injury may be an important feature in the process of TLS.
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http://dx.doi.org/10.1038/s41598-021-88912-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102476PMC
May 2021

Cognitive Impairment in Survivors of Pediatric Acute Lymphoblastic Leukemia Treated With Chemotherapy Only.

J Clin Oncol 2021 06 22;39(16):1705-1717. Epub 2021 Apr 22.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.

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http://dx.doi.org/10.1200/JCO.20.02322DOI Listing
June 2021

Use of Chronic Prescription Medications and Prevalence of Polypharmacy in Survivors of Childhood Cancer.

Front Oncol 2021 1;11:642544. Epub 2021 Apr 1.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.

Background: As survivors of childhood cancer age, development of cancer treatment-related chronic health conditions often occur. This study aimed to describe the pattern of chronic prescription medication use and identify factors associated with polypharmacy among survivors of childhood cancer.

Methods: This was a retrospective study conducted at the pediatric oncology long-term follow-up clinic in Hong Kong. Eligible subjects included survivors who were (1) diagnosed with cancer before 18 years old, (2) were at least 3 years post-cancer diagnosis and had completed treatment for at least 30 days, and (3) receiving long-term follow-up care at the study site between 2015 and 2018. Dispensing records of eligible survivors were reviewed to identify medications taken daily for ≥30 days or used on an "as needed" basis for ≥6 months cumulatively within the past 12-month period. Polypharmacy was defined as the concurrent use of ≥5 chronic medications. Multivariable log-binomial modeling was conducted to identify treatment and clinical factors associated with medication use pattern and polypharmacy.

Results: This study included 625 survivors (mean current age = 17.9 years, standard deviation [SD] = 7.2 years) who were 9.2 [5.2] years post-treatment. Approximately one-third (n = 219, 35.0%) of survivors were prescribed at least one chronic medication. Frequently prescribed medication classes include systemic antihistamines (26.5%), sex hormones (19.2%), and thyroid replacement therapy (16.0%). Overall prevalence of polypharmacy was 5.3% (n = 33). A higher rate of polypharmacy was found in survivors of CNS tumors (13.6%) than in survivors of hematological malignancies (4.3%) and other solid tumors (5.3%) ( = .0051). Higher medication burden was also observed in survivors who had undergone cranial radiation (RR = 6.31; 95% CI = 2.75-14.49) or hematopoietic stem-cell transplantation (HSCT) (RR = 3.53; 95% CI = 1.59-7.83).

Conclusion: Although polypharmacy was observed in a minority of included survivors of childhood cancer, chronic medication use was common. Special attention should be paid to survivors of CNS tumors and survivors who have undergone HSCT or cranial radiation. These individuals should be monitored closely for drug-drug interactions and adverse health outcomes that may result from multiple chronic medications, particularly during hospitalization in an acute care setting.
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http://dx.doi.org/10.3389/fonc.2021.642544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047635PMC
April 2021

Prognostic factors for CNS control in children with acute lymphoblastic leukemia treated without cranial irradiation.

Blood 2021 Jul;138(4):331-343

Departments of Oncology, Global Pediatric Medicine, Biostatistics and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN.

To identify the prognostic factors that are useful to improve central nervous system (CNS) control in children with acute lymphoblastic leukemia (ALL), we analyzed the outcome of 7640 consecutive patients treated on Chinese Children's Cancer Group ALL-2015 protocol between 2015 and 2019. This protocol featured prephase dexamethasone treatment before conventional remission induction and subsequent risk-directed therapy, including 16 to 22 triple intrathecal treatments, without prophylactic cranial irradiation. The 5-year event-free survival was 80.3% (95% confidence interval [CI], 78.9-81.7), and overall survival 91.1% (95% CI, 90.1-92.1). The cumulative risk of isolated CNS relapse was 1.9% (95% CI, 1.5-2.3), and any CNS relapse 2.7% (95% CI, 2.2-3.2). The isolated CNS relapse rate was significantly lower in patients with B-cell ALL (B-ALL) than in those with T-cell ALL (T-ALL) (1.6%; 95% CI, 1.2-2.0 vs 4.6%; 95% CI, 2.9-6.3; P < .001). Independent risk factors for isolated CNS relapse included male sex (hazard ratio [HR], 1.8; 95% CI, 1.1-3.0; P = .03), the presence of BCR-ABL1 fusion (HR, 3.8; 95% CI, 2.0-7.3; P < .001) in B-ALL, and presenting leukocyte count ≥50×109/L (HR, 4.3; 95% CI, 1.5-12.2; P = .007) in T-ALL. Significantly lower isolated CNS relapse was associated with the use of total intravenous anesthesia during intrathecal therapy (HR, 0.2; 95% CI, 0.04-0.7; P = .02) and flow cytometry examination of diagnostic cerebrospinal fluid (CSF) (HR, 0.2; 95% CI, 0.06-0.6; P = .006) among patients with B-ALL. Prephase dexamethasone treatment, delayed intrathecal therapy, use of total intravenous anesthesia during intrathecal therapy, and flow cytometry examination of diagnostic CSF may improve CNS control in childhood ALL. This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706).
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http://dx.doi.org/10.1182/blood.2020010438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323972PMC
July 2021

Identifying Priorities for Harmonizing Guidelines for the Long-Term Surveillance of Childhood Cancer Survivors in the Chinese Children Cancer Group (CCCG).

JCO Glob Oncol 2021 02;7:261-276

Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.

Purpose: Survivors of childhood cancer often experience treatment-related chronic health conditions. Given its vast population, China shares a large proportion of the global childhood cancer burden. Yet, screening and treatment of late effects in survivors of childhood cancer remain underaddressed in most regions of China. This study aimed to identify high-priority late effects for harmonizing screening guidelines within the Chinese Children's Cancer Group (CCCG), as well as barriers and enablers of the implementation of surveillance recommendations in local practice.

Methods: To establish clinical consensus, 12 expert panelists who represent major institutions within the CCCG completed a Delphi survey and participated in a focus group discussion. The survey solicited ratings of the prevalence, severity, and priority for screening of 45 late effects. Major themes identified from the focus group were analyzed using thematic analysis.

Results: The Delphi survey identified eight high-priority late effects for harmonization within CCCG: osteonecrosis, osteoporosis, left ventricular dysfunction, secondary brain tumors, treatment-related myeloid leukemia, gonadal dysfunction, growth hormone deficiency, and neurocognitive deficits. The common barriers to implementing survivorship programs include lack of support and resources for clinicians to provide follow-up care. Patients were also concerned about privacy issues and lacked awareness of late effects. Many institutions also lacked rehabilitation expertise and referral pathways.

Conclusion: By identifying obstacles related to the professional setting, patient behavior, and organization of care, our study identified resources and a framework for establishing collaborative strategies to facilitate follow-up care of childhood cancer survivors in China.
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http://dx.doi.org/10.1200/GO.20.00534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081494PMC
February 2021

Inotuzumab ozogamicin in infants and young children with relapsed or refractory acute lymphoblastic leukaemia: a case series.

Br J Haematol 2021 06 2;193(6):1172-1177. Epub 2021 Feb 2.

Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

No data on inotuzumab ozogamicin (InO) in infant acute lymphoblastic leukaemia (ALL) have been published to date. We collected data internationally on infants/young children (<3 years) with ALL treated with InO. Fifteen patients (median 4.4 months at diagnosis) received InO due to relapsed or refractory (R/R) disease. Median percentage of CD22 blasts was 72% (range 40-100%, n = 9). The median dose in the first course was 1.74 mg/m (fractionated). Seven patients (47%) achieved complete remission; one additional minimal residual disease (MRD)-positive patient became MRD-negative. Six-month overall survival was 47% (95% confidence interval [CI] 27-80%). Two patients developed veno-occlusive disease after transplant. Further evaluation of InO in this subgroup of ALL is justified.
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http://dx.doi.org/10.1111/bjh.17333DOI Listing
June 2021

An international retrospective study for tolerability of 6-mercaptopurine on NUDT15 bi-allelic variants in children with acute lymphoblastic leukemia.

Haematologica 2021 07 1;106(7):2026-2029. Epub 2021 Jul 1.

Department of Transplantation and Cell Therapy, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan; Department of Pediatric Hematology and Oncology Research, National Center for Child Health and Development, Tokyo, Japan; Department of Pediatrics, the University of Tokyo, Tokyo.

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http://dx.doi.org/10.3324/haematol.2020.266320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252943PMC
July 2021

Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol.

BMC Cancer 2021 Jan 13;21(1):59. Epub 2021 Jan 13.

Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.

Background: The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality (TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL.

Methods: The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs.

Results: The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2%) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day 33 positive group (n=7) was 28.6%, while in the MRD Day 33 negative group (n=67) was 7.5% (p=0.129).

Conclusions: The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.
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http://dx.doi.org/10.1186/s12885-020-07752-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805214PMC
January 2021

Clinical Implications of Minimal Residual Disease Detection in Infants With -Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol.

J Clin Oncol 2021 02 6;39(6):652-662. Epub 2021 Jan 6.

Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

Purpose: Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with -rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide).

Materials And Methods: MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged , immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10), and high (≥ 5 × 10).

Results: EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively ( = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively ( < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively ( < .0001), while for myeloid-style-treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9).

Conclusion: This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% 23.2%), whereas patients with low EOI MRD may benefit from ALL-like consolidation (DFS 78.2% 45.0%). Patients with positive EOC MRD had dismal outcomes. These findings will be used for treatment interventions in the next Interfant protocol.
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http://dx.doi.org/10.1200/JCO.20.02333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196086PMC
February 2021

Longitudinal dynamics of gut bacteriome, mycobiome and virome after fecal microbiota transplantation in graft-versus-host disease.

Nat Commun 2021 01 4;12(1):65. Epub 2021 Jan 4.

Center for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China.

Fecal microbiota transplant (FMT) has emerged as a potential treatment for severe colitis associated with graft-versus-host disease (GvHD) following hematopoietic stem cell transplant. Bacterial engraftment from FMT donor to recipient has been reported, however the fate of fungi and viruses after FMT remains unclear. Here we report longitudinal dynamics of the gut bacteriome, mycobiome and virome in a teenager with GvHD after receiving four doses of FMT at weekly interval. After serial FMTs, the gut bacteriome, mycobiome and virome of the patient differ from compositions before FMT with variable temporal dynamics. Diversity of the gut bacterial community increases after each FMT. Gut fungal community initially shows expansion of several species followed by a decrease in diversity after multiple FMTs. In contrast, gut virome community varies substantially over time with a stable rise in diversity. The bacterium, Corynebacterium jeikeium, and Torque teno viruses, decrease after FMTs in parallel with an increase in the relative abundance of Caudovirales bacteriophages. Collectively, FMT may simultaneously impact on the various components of the gut microbiome with distinct effects.
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http://dx.doi.org/10.1038/s41467-020-20240-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782528PMC
January 2021

Astragalus polysaccharide has a protective effect on hematopoiesis in an irradiated mouse model and decreases apoptosis in megakaryocytes.

Mol Med Rep 2021 01 12;23(1). Epub 2020 Nov 12.

Research Center of The Seventh Affiliated Hospital, Sun Yat‑sen University, Shenzhen, Guangdong 518107, P.R. China.

Huangqi, the dried root of Radix Astragali, is an essential herb in Traditional Chinese Medicine and has been used to promote hematopoiesis for centuries. Astragalus polysaccharide (ASPS), the bioactive compound of Huangqi, serves a crucial role in hematopoiesis. The aim of the present study was to investigate the hematopoietic effects, in particular the thrombopoietic effects, and the molecular mechanisms of ASPS using an irradiation‑induced myelosuppressive mouse model. Colony‑forming unit assays, flow cytometric analysis of apoptosis, ELISAs, Giemsa staining and western blotting were performed to determine the hematopoietic and anti‑apoptotic effects of ASPS. The results demonstrated that ASPS enhanced the recovery of red blood cells at day 21 following treatment, as well as platelets and white blood cells at day 14. In addition, ASPS promoted colony formation in all lineages (megakaryocytes, granulocyte monocytes, erythroid cells and fibroblasts). The morphological study of the bone marrow demonstrated that tri‑lineage hematopoiesis was preserved in the ASPS‑ and thrombopoietin (TPO)‑treated groups compared with the control group. The overall cellularity (mean total cell count/area) of the ASPS‑treated group was similar to that of the TPO‑treated group. Additionally, in vitro experiments indicated that treatment with 100 µg/ml ASPS exhibited the maximum effect on colony formation. ASPS attenuated cell apoptosis in megakaryocytic cells via inhibiting the mitochondrial caspase‑3 signaling pathway. In conclusion, ASPS promoted hematopoiesis in irradiated myelosuppressive mice possibly via enhancing hematopoietic stem/progenitor cell proliferation and inhibiting megakaryocytes apoptosis.
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http://dx.doi.org/10.3892/mmr.2020.11653DOI Listing
January 2021

Upfront consolidation treatment with I-mIbG followed by myeloablative chemotherapy and hematopoietic stem cell transplantation in high-risk neuroblastoma.

Pediatr Investig 2020 Sep 27;4(3):168-177. Epub 2020 Sep 27.

Department of Paediatrics The Chinese University of Hong Kong Hong Kong China.

Importance: I-metaiodobenzylguanidine (I-mIBG) has a significant targeted antitumor effect for neuroblastoma. However, currently there is a paucity of data for the use of I-mIBG as a "front-line" therapeutic agent in those patients with newly diagnosed high-risk neuroblastoma as part of the conditioning regimen for myeloablative chemotherapy (MAC).

Objective: To evaluate the feasibility of upfront consolidation treatment with I-mIBG plus MAC and hematopoietic stem cell transplantation (HSCT) in high-risk neuroblastoma patients.

Methods: A retrospective, single-center study was conducted from 2003-2019 on newly diagnosed high-risk neuroblastoma patients without progressive disease (PD) after the completion of induction therapy. They received I-mIBG infusion and MAC followed by HSCT.

Results: A total of 24 high-risk neuroblastoma patients were enrolled with a median age of 3.0 years at diagnosis. After receiving this sequential consolidation treatment, 3 of 13 patients who were in partial response (PR) before I-mIBG treatment achieved either complete response (CR) ( 1) or very good partial response (VGPR) ( 2) after HSCT. With a median follow-up duration of 13.0 months after I-mIBG therapy, the 5-year event-free survival and overall survival rates estimated were 29% and 38% for the entire cohort, and 53% and 67% for the patients who were in CR/VGPR at the time of I-mIBG treatment.

Interpretation: Upfront consolidation treatment with I-mIBG plus MAC and HSCT is feasible and tolerable in high-risk neuroblastoma patients, however the survival benefit of this I-mIBG regimen is only observed in the patients who were in CR/VGPR at the time of I-mIBG treatment.
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http://dx.doi.org/10.1002/ped4.12216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520103PMC
September 2020

Treatment of childhood cancer in China: Current status and future direction.

Pediatr Investig 2020 Sep 27;4(3):153-156. Epub 2020 Sep 27.

Department of Pediatric Oncology Sun Yat-Sen University Cancer Center Guangzhou China.

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http://dx.doi.org/10.1002/ped4.12210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520102PMC
September 2020

Double-unit unrelated cord blood transplantation for thalassemia major: Comparison with HLA-identical sibling bone marrow transplantation.

Pediatr Transplant 2021 May 2;25(3):e13901. Epub 2020 Nov 2.

Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.

UCBT recipients with TM are at high risk of EF related to low number of stem cells and prior alloimmunization after multiple blood transfusions. Here, we evaluated the safety and efficacy of double-unit UCBT using TT-containing conditioning regimens in TM. Retrospective analysis of children who underwent double-unit UCBT for TM in the Prince of Wales Hospital between August 2007 and January 2017, and outcome of double-unit UCBT for TM was compared with outcome of HLA-matched sibling BMT. Ten patients, median age 4.2 years, received double-unit UCBT. All patients except one engrafted at a median of 19 days. None of the patients with successful engraftment had grade III or IV aGVHD. Among nine patients with successful engraftment, six of nine patients evaluable after day 100 developed cGVHD. All patients with cGVHD were well controlled after treatment with steroids and/or supportive care and maintained good quality of life. In comparison with patients receiving BMT, those given UCBT had slower platelet recovery, and more cGVHD. With a median follow-up of 272 months after BMT and 84 months after UCBT, the 8-year OS after BMT and UCBT was 92% and 90% (P = .84), whereas 8-year DFS after BMT and UCBT was 87% and 80% (P = .54). UCB could be an acceptable source of stem cells for transplantation of TM patients when HLA-matched family bone marrow donors are NA.
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http://dx.doi.org/10.1111/petr.13901DOI Listing
May 2021

t(1;22)(p13;q13) Acute Megakaryoblastic Leukemia Complicated by Hepatic Fibrosis: Antifibrosis Therapy?

J Pediatr Hematol Oncol 2020 Oct 28. Epub 2020 Oct 28.

Departments of Paediatrics.

Background: There is no established effective treatment for patients with t(1;22)(p13;q13) acute megakaryoblastic leukemia (AMKL) and hepatic fibrosis.

Observation: Here we report the outcomes of 2 t(1;22)(p13;q13) AMKL patients with hepatic fibrosis. One patient died from liver failure despite the control of leukemia. The other patient was successfully treated with reduced-intensity chemotherapy and antifibrosis therapy with tretinoin and α-tocopheryl acetate, the hepatic fibrosis resolved and leukemia was in remission for 3 years.

Conclusions: Reduced-intensity chemotherapy plus antifibrosis therapy with tretinoin and α-tocopheryl acetate could be a treatment option for these patients with t(1;22)(p13;q13) AMKL and hepatic fibrosis.
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http://dx.doi.org/10.1097/MPH.0000000000001986DOI Listing
October 2020

Health Behaviors of Chinese Childhood Cancer Survivors: A Comparison Study with Their Siblings.

Int J Environ Res Public Health 2020 08 24;17(17). Epub 2020 Aug 24.

Department of Paediatrics & Adolescent Medicine, Princess Margaret Hospital, Hong Kong, China.

This study aimed to compare health behaviors between the childhood cancer survivors (CCS) and their sibling controls and to examine the pattern of health behaviors of the Hong Kong Chinese CCS and its associations with their health-related quality of life and psychological distress. A cross-sectional telephone survey was conducted. A total of 614 CCS and 208 sibling controls participated in this study. Patterns of health behaviors including lifestyle behaviors, cancer screening practices, and insurance coverage were compared. Multivariate regression analyses were performed for examining factors associated with health behaviors in CCS. CCS had less alcohol consumption when compared with their sibling controls (adjusted odds ratio (AOR) = 0.65, = 0.035). The sibling controls were more likely to have cancer screening practices (AOR = 0.38, = 0.005) and health (AOR = 0.27, < 0.001) and life insurance coverage (AOR = 0.38, < 0.001). Among the CCS, those who were male, having a job or higher education, shorter time since diagnosis, and type of cancer suffered were significantly associated with alcohol consumption. Those CCS who were drinkers indicated poorer mental health ( = 0.004) and more psychological distress. Female CCS undertaking cancer screening were more likely to be employed, married/cohabiting, and have received intensive cancer treatment. This study reveals that Chinese childhood cancer survivors are less likely to engage in unhealthy lifestyle behaviors, insurance coverage and cancer screening, when compared with their siblings. : It is crucial for healthcare professionals to identify strategies or target interventions for raising CCS's awareness of their cancer risks and healthy lifestyle throughout their life.
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http://dx.doi.org/10.3390/ijerph17176136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503484PMC
August 2020

Lymphoblastic predominance of blastic phase in children with chronic myeloid leukaemia treated with imatinib: A report from the I-CML-Ped Study.

Eur J Cancer 2020 09 13;137:224-234. Epub 2020 Aug 13.

Inserm CIC 1402, University Hospital, Poitiers, France.

Background: Chronic myeloid leukaemia (CML) is a rare disease in children. The frequency and outcome of children evolving to accelerated phase (AP) or blastic phase (BP) under treatment with imatinib is unknown. The aim of the current study is to assess the incidence of progression from CML in chronic phase with imatinib frontline in a paediatric setting and describe the management and outcome of these patients.

Patients And Methods: In the I-CML-Ped Study database (www.clinicaltrials.gov, #NCT01281735), 19 of 339 paediatric patients in chronic phase treated with imatinib in the frontline evolved to CML-AP or CML-BP.

Results: With a median follow-up of 38 months (range: 2-190 months), the cumulative incidence of progression at 1 and 3 years was 3% (confidence interval [CI] 95%: 1-5%) and 7% (CI 95%: 4-11%), respectively. We observed a large predominance of lymphoid-BP (70%) over myeloid-BP (30%) with imatinib in frontline therapy. Sixteen patients underwent haematopoietic stem cell transplantation, and eight were treated with a tyrosine kinase inhibitor after transplant. Only the transplanted patients are alive. The 5-year overall survival rate of children with CML-AP/BP is 44%, with no statistical difference between the lymphoid-BP and myeloid-BP outcome.

Conclusion: Children evolving to AP or BP under treatment with imatinib have a very poor prognosis with an overall survival under 50%, much worse than children with advanced phase at diagnosis.
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http://dx.doi.org/10.1016/j.ejca.2020.06.024DOI Listing
September 2020

Life Functioning in Chinese Survivors of Childhood Cancer in Hong Kong.

J Adolesc Young Adult Oncol 2021 06 27;10(3):326-335. Epub 2020 Jul 27.

Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.

Evidence on self-care ability and occupational outcomes in Chinese survivors of childhood cancer is clearly lacking. This study aims to identify clinical and behavioral factors associated with poor life functioning in this population. This was a cross-sectional study conducted at an ambulatory clinic of a public hospital in Hong Kong. Licensed occupational therapists administered the Life Functioning Assessment Inventory on survivors diagnosed with cancer <19 years old and ≥5 years post-diagnosis. Survivors' career development self-efficacy, subjective happiness, and motivation were evaluated using structured questionnaires. Clinical information was obtained from medical records. Multivariable linear regression was used to evaluate factors associated with life functioning outcomes, adjusting for clinically relevant variables. Eighty survivors were recruited (58.7% male; age at diagnosis: 6.7 [standard deviation (SD) = 4.8] years; age at evaluation: 24.4 [SD = 6.5] years). Compared to survivors of leukemia, survivors of brain tumor performed worse in social functioning ( = -0.79, standard error [SE] = 0.36;  = 0.034). Survivors who had been treated with cranial radiation also had lower worker life functioning than those who had not ( = -0.91, SE = 0.031;  = 0.021). Higher activity motivation was significantly associated with better leisure functioning ( = 0.086, SE = 0.03;  = 0.008), social functioning ( = 0.036, SE = 0.02;  = 0.036), and career development self-efficacy ( = 1.04, SE = 0.26;  < 0.0001). Survivors of brain tumors and survivors who were treated with radiation have poorer life functioning, particularly in social and work domains. Future work includes validating the study findings in a larger cohort of survivors in Hong Kong. Addressing modifiable behavioral factors include motivating survivors to engage in meaningful activities that contribute to self-care and participation in society, as well as providing at-risk survivors with ongoing support from community vocational services.
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http://dx.doi.org/10.1089/jayao.2020.0047DOI Listing
June 2021
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