Examining patterns of traditional Chinese medicine use in pediatric oncology: A systematic review, meta-analysis and data-mining study / 中西医结合学报

BACKGROUND@#Traditional Chinese medicine (TCM) is becoming a popular complementary approach in pediatric oncology. However, few or no meta-analyses have focused on clinical studies of the use of TCM in pediatric oncology.@*OBJECTIVE@#We explored the patterns of TCM use and its efficacy in children with cancer, using a systematic review, meta-analysis and data mining study.@*SEARCH STRATEGY@#We conducted a search of five English (Allied and Complementary Medicine Database, Embase, PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and four Chinese databases (Wanfang Data, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and VIP Chinese Science and Technology Periodicals Database) for clinical studies published before October 2021, using keywords related to "pediatric," "cancer," and "TCM."@*INCLUSION CRITERIA@#We included studies which were randomized controlled trials (RCTs) or observational clinical studies, focused on patients aged < 19 years old who had been diagnosed with cancer, and included at least one group of subjects receiving TCM treatment.@*DATA EXTRACTION AND ANALYSIS@#The methodological quality of RCTs and observational studies was assessed using the six-item Jadad scale and the Effective Public Healthcare Panacea Project Quality Assessment Tool, respectively. Meta-analysis was used to evaluate the efficacy of combining TCM with chemotherapy. Study outcomes included the treatment response rate and occurrence of cancer-related symptoms. Association rule mining (ARM) was used to investigate the associations among medicinal herbs and patient symptoms.@*RESULTS@#The 54 studies included in this analysis were comprised of RCTs (63.0%) and observational studies (37.0%). Most RCTs focused on hematological malignancies (41.2%). The study outcomes included chemotherapy-induced toxicities (76.5%), infection rate (35.3%), and response, survival or relapse rate (23.5%). The methodological quality of most of the RCTs (82.4%) and observational studies (80.0%) was rated as "moderate." In studies of leukemia patients, adding TCM to conventional treatment significantly improved the clinical response rate (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.49-4.36), lowered infection rate (OR = 0.23; 95% CI = 0.13-0.40), and reduced nausea and vomiting (OR = 0.13; 95% CI = 0.08-0.23). ARM showed that Radix Astragali, the most commonly used medicinal herb (58.0%), was associated with treating myelosuppression, gastrointestinal complications, and infection.@*CONCLUSION@#There is growing evidence that TCM is an effective adjuvant therapy for children with cancer. We proposed a checklist to improve the quality of TCM trials in pediatric oncology. Future work will examine the use of ARM techniques on real-world data to evaluate the efficacy of medicinal herbs and drug-herb interactions in children receiving TCM as a part of integrated cancer therapy.

Management of Malignancies Developing in AYA / 임상소아혈액종양

Adolescent and young adult (AYA) with cancers have distinct spectrum of cancers as compared to younger and older age groups. The definition of age limits of AYA varies among countries, from 15-25 years to 12-39 years. The differences in age definition lead to variation in report of incidence, types of cancers and survival. In younger AYA patients, hematological malignancies are leading cause of cancers. In older AYA patients, testicular cancers are common in males while breast cancers and cervical cancers are predominant types in females. There is increasing incidence of AYA cancers worldwide in the past two decades. Overall survival and treatment outcome of AYA cancer has been improving in the last few decades. Specialized centers for AYA with cancers provide more comprehensive care and have been reported to have superior outcome. About 80% of AYA with cancers survive at 5 years after diagnosis but they are higher risk of developing second malignancies. Barriers to AYA cancer treatment included social economic status, insurance system and accessibility to clinical trials. Survivors of AYA cancers are also at higher risk dying from cardiovascular diseases and respiratory diseases. Survivorship program should be in place to enhance education and surveillance.

Management of Malignancies Developing in AYA / 임상소아혈액종양

Adolescent and young adult (AYA) with cancers have distinct spectrum of cancers as compared to younger and older age groups. The definition of age limits of AYA varies among countries, from 15-25 years to 12-39 years. The differences in age definition lead to variation in report of incidence, types of cancers and survival. In younger AYA patients, hematological malignancies are leading cause of cancers. In older AYA patients, testicular cancers are common in males while breast cancers and cervical cancers are predominant types in females. There is increasing incidence of AYA cancers worldwide in the past two decades. Overall survival and treatment outcome of AYA cancer has been improving in the last few decades. Specialized centers for AYA with cancers provide more comprehensive care and have been reported to have superior outcome. About 80% of AYA with cancers survive at 5 years after diagnosis but they are higher risk of developing second malignancies. Barriers to AYA cancer treatment included social economic status, insurance system and accessibility to clinical trials. Survivors of AYA cancers are also at higher risk dying from cardiovascular diseases and respiratory diseases. Survivorship program should be in place to enhance education and surveillance.

Second malignant neoplasms in childhood cancer survivors in a tertiary paediatric oncology centre in Hong Kong, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Childhood cancer survivors were at risk of development of second malignant neoplasms. The aim of this study is to evaluate the incidence, risk factors and outcome of second malignant neoplasms in childhood cancer survivors in a tertiary paediatric oncology centre in Hong Kong, China.</p><p><b>METHODS</b>We performed a retrospective review of patients with childhood cancer treated in Children's Cancer Centre in Prince of Wales Hospital, Hong Kong, China between May 1984 and June 2009. Case records of patients who developed second malignant neoplasms were reviewed.</p><p><b>RESULTS</b>Totally 1374 new cases aged less than 21-year old were treated in our centre in this 25-year study period. Twelve cases developed second malignant neoplasms with 10-year and 20-year cumulative incidence of 1.3% (95% confidence interval 0.3% - 2.3%) and 2.9% (95% confidence interval 1.1% - 4.7%) respectively. Another 4 cases were referred to us from other centres for the management of second malignant neoplasms. In this cohort of 16 children with second malignant neoplasms, the most frequent second malignant neoplasms were acute leukemia or myelodysplastic syndrome (n = 6) and central nervous system tumor (n = 4). Median interval between diagnosis of primary and second malignant neoplasms was 7.4 years (range 2.1 - 13.3 years). Eight patients developed second solid tumor within the previous irradiated field. Radiotherapy significantly increased the risk of development of second solid tumor in patients with acute lymphoblastic leukemia (P = 0.027). Seven out of 16 patients who developed second malignant neoplasms had a family history of cancer among the first or second-degree relatives. Nine patients died of progression of second malignant neoplasms, mainly resulted from second central nervous system tumor and osteosarcoma.</p><p><b>CONCLUSIONS</b>Cumulative incidence of second cancer in our centre was comparable to western countries. Radiotherapy was associated with second solid tumour among patients with acute lymphoblastic leukemia. Patients who developed second brain tumor and osteosarcoma had a poor outcome.</p>

Detection of minimal residual disease in childhood acute lymphoblastic leukemia by using real-time quantitative PCR / 中国实验血液学杂志

This study was purposed to detect the minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) by using real time quantitative PCR (RQ-PCR) . The Ig and TCR gene rearrangements were amplified by using 18 primer sets in B-ALL, 8 primer sets in T-ALL; the ALL-MRD levels were quantified by using RQ-PCR with SYBR green dye staining and clone specific Ig/TCR gene rearrangements as molecular markers. The results indicated that there were 8 cases showing gene rearrangements in 9 B-ALL patients, marker detection rate for all samples was 88.8%, the MRD level on day 33 during induction treatment decreased significantly. It is concluded that Ig/TCR gene rearrangements can be used as a marker to detect MRD in childhood ALL; the technique of QR-PCR with SYBR green dye staining is reliable, relatively sensitive and easy performable method which can be used in routine detection for childhood ALL.

Identification of TPO receptors on central nervous system-a preliminary report / 中国实验血液学杂志

To identify the expression of thrombopoietin (TPO) receptors (c-mpl) on central nervous system (CNS) and to evaluate the role of TPO on neural cell proliferation and protection, immunohistochemical staining, RT-PCR, MTT, and annexin-V methods were used in this study. The results showed the expression of TPO receptor on human CNS and murine neural cells. C-mpl mRNA was identified in human cerebral hemispheres and cerebellum, and mouse neural cell line C17.2 by RT-PCR. C-mpl was also confirmed in human cerebral hemispheres by immunohistostaining with con-focal microscopy. Furthermore, TPO had a stimulating effect on the growth of in vitro neural cell C17.2 by MTT assay. The anti-apoptotic effect of TPO on C17.2 cells was also demonstrated by staining with annexin-V and PI. In conclusion, the first evidence showed the expression of TPO receptor c-mpl in central nervous system. Moreover, the effect of TPO on neural cell proliferation and anti-apoptosis was also demonstrated on in vitro neural cells.

The effect of SARS coronavirus on blood system: its clinical findings and the pathophysiologic hypothesis / 中国实验血液学杂志

Severe acute respiratory syndrome (SARS) has recently recognized as a new human infectious disease. A novel coronavirus was identified as the causative agent of SARS. This report summarizes the hematological findings in SARS patients and proposes a hypothesis for the pathophysiology of SARS coronavirus related abnormal hematopoiesis. Hematological changes in patients with SARS were common and included lymphopenia (68% - 90% of adults; 100% of children, n = 10), thrombocytopenia (20% - 45% of adults, 50% of children), and leukopenia (20% - 34% of adults, 70% of children). The possible mechanisms of this coronavirus on blood system may include (1) directly infect blood cells and bone marrow stromal cells via CD13 or CD66a; and/or (2) induce auto-antibodies and immune complexes to damage these cells. In addition, lung damage in SARS patients may also play a role on inducing thrombocytopenia by (1) increasing the consumption of platelets/megakaryocytes; and/or (2) reducing the production of platelets in the lungs. Since the most common hematological changes in SARS patients were lymphopenia and immunodeficiency. We postulate that hematopoietic growth factors such as G-CSF, by mobilizing endogenous blood stem cells and endogenous cytokines, could become a hematological treatment for SARS patients, which may enhance the immune system against these virus.

The Immunological Study of Megakaryocytes / 中国实验血液学杂志

The immunological role of megakaryocytes is not well known. This project studies the involvement of megakaryocytes on immuno-inflammatory processes and the possible mechanism via the adhesion molecule CD36 and the synthesis of relevant cytokines. The expression of adhesion protein CD36 on human platelets, megakaryocytes and megakaryocytic cell lines (Meg-01, Dami, CHRF-288-11 and M-07e) was analyzed by using flow cytometry, ELISA and immunocytochemical methods. The expression of interleukin-1 (IL-1) to interleukin-10 (IL-10), TNF-alpha, TNF-gamma and IFN-gamma on the four megakaryocytic cell lines was also determined by RT-PCR. The effect of IL-1beta, IL-3, IL-6 and TPO on murine megakaryocyte colony formation (CFU-MK) was studied by using a plasma clot culture system. The CFU-MK was confirmed by acetylcholine esterase staining. The results showed that: (1) CD36 was expressed on platelets, megakaryocytes and the four megakaryocytic cell lines, the relative expression level is as follows: platelets > megakaryocytes > Meg-01 > Dami > CHRF-288-11 > M-07e, suggesting that the level of CD36 expression correlates with the degree of maturity of megakaryocytic differentiation; (2) inflammatory cytokines TNF-alpha, IL-1beta, IL-3 and IL-6 were detected in all the four megakaryocytic cell lines, suggesting that different stages of megakaryocytes can be as a source of inflammatory cytokines; and (3) IL-1beta, IL-3 and IL-6, as well as TPO, play a stimulating effect on CFU-MK formation, suggesting that there is an "autocrine" effect on megakaryocytopoiesis. The data obtained suggest that megakaryocytes may involve in immuno-inflammatory processes via the synthesis of platelet adhesion molecules and inflammatory cytokines.