Fig 1 - uploaded by Ye Jee Shim
Content may be subject to copyright.
Flow diagram of patients. APL, acute promyelocytic leukemia; Ara-C, anthracycline with or without cytosine arabinoside; ATRA, all-trans retinoic acid; CR, complete remission; CTx, chemotherapy; F/U, follow-up.
Source publication
Purpose:
Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.
Materials and methods:
Seventy-nine pediatric APL patients diagnosed from January 2009 to Dec...
Context in source publication
Context 1
... therapeutic responses are described in Table 2 and Fig. 1. Seventy-six patients received induction treatment, excluding one patient whose follow-up was discontinued after diagnosis and two patients who died of severe bleeding prior to treatment; one was due to intracranial hemorrhage (ICH), and the other was due to pulmonary hemorrhage. Five patients (6.6%) died during induction therapy (3 ...
Citations
... There was no difference in median age between the standard-and high-risk groups [43]. These patterns have been maintained across multiple clinical trials and are comparable to risk breakdown in adult studies [44,45]. Thus, children do not appear to be more likely to have a high or standard risk of disease compared to adults. ...
... The severity can range from isolated lab abnormalities to severe bleeding, including intracranial or pulmonary hemorrhage, which can be lethal. Severe bleeding events have been reported in up to 15% of children with APL, leading to early death in up to 10% [43][44][45]. In particular, central nervous system (CNS) haemorrhage can be challenging to diagnose in young children who are unable to communicate symptoms early in the disease process. ...
Simple Summary
This review summarizes various unique aspects of managing APL in very elderly and pediatric patients, particularly treatment with ATO, toxicities, and dose modifications.
Abstract
Tailored treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the outcome of acute promyelocytic leukemia (APL) from a uniformly fatal disease to one of the most curable malignant diseases in humans. Due to its high efficacy, ATO/ATRA is the standard first-line therapy in younger adult, non-high-risk APL patients. However, early death is still a major issue in APL, particularly in older patients. Thus, rapid diagnostics, immediate access to ATRA-based therapy, and supportive care are of utmost importance. Nevertheless, challenging situations occur, particularly in patients excluded from controlled studies with clinical knowledge mainly based on case reports and registries. Besides the treatment of newly diagnosed patients, managing toxicities and complications remains challenging. This review discusses the approach to the treatment of APL in elderly and pediatric patients.
... Furthermore, APL is a rare type of leukemia, accounting for only 5-10% of pediatric AML cases [1]. A recent study conducted in patients aged ＜18 y from Korea who were diagnosed with AML from 2009 to 2016 reported that 10% of them were diagnosed with APL [2]. APL is usually associated with coagulopathy and thrombotic complications [3], which increase the risk of fatal hemorrhage. ...
... Three of the seven cases found in the literature and two of our three patients died because of brain haemorrhage. In a recent study of 79 paediatric acute promyelocytic leukaemia patients, five (6.6%) died during induction chemotherapy, and the causes of death were three intracranial haemorrhages, one cerebral infarction, and one sepsis [15]. Thus, it seems that intracranial haemorrhage is a frequent cause of death in acute leukaemia cases. ...
Acute myeloid leukaemia (AML) is a rare haematologic cancer with a rapid increase in blast cells, which need to be rapidly diagnosed and treated. The aim of this report is to analyse the rare phenomenon of AML diagnosed at autopsy after sudden death. We report three cases of AML and perform a literature review using the mesh terms “sudden death” and “leukaemia”. We report the cases of three young women diagnosed with AML only after autopsy. We found seven articles which reported sudden death due to AML diagnosed at autopsy. Diagnosis of AML during autopsy is rare but can raise forensic issues. A complete autopsy with pathology analysis is needed.
... An initial high leukocyte count is known to be unfavorable factor for induction response. In agreement with what reported in other APL trials performed in HICs and LICs, where ATRA was associated with one or more chemotherapeutic agents in induction, a higher presenting WBC count is significantly associated with early death (HR 75% vs LR 25%; p ¼ 0.011) [10,[15][16][17]. In an international retrospective study including 608 children with newly diagnosed APL, the diagnostic leukocyte count !10.0 Â 10 9 /L, was an independent prognostic factor for induction thrombohemorrhagic death [18]. ...
... In the present study, 50/118 (42%) children (41% of the evaluable patients) presented a WBC count ! 10 Â 10 9 /L, as reported in other pediatric series. In the ICC-APL-01 protocol that included 258 children from 8 Pediatric Cooperative groups/countries, the incidence of HR was 42% [5] and in the recent retrospective multicenter Korean pediatric APL study, including 79 patients, the incidence of HR was 38% [17]. Hyperleukocytosis is also more frequently a cause of DS, responsible for death in 3 cases of this series. ...
Modern treatments have dramatically improved the prognosis of childhood acute promyelocytic leukemia (APL). This progress has not yielded equivalent benefit in developing countries, where biological studies and supportive cares are insufficient and often unavailable. Since 2003, an all-trans retinoic (ATRA)-based, risk-adapted protocol was initiated in Baghdad. Patients were defined: high-risk with WBC ≥10 × 109/L and standard-risk with WBC <10 × 109/L. ATRA was included in induction and maintenance and, from 2010, in consolidation. Of 429 pediatric acute myeloid leukemia (September 2003-August 2019), 118 (27.5%) were APL. Six children died before therapy, 4 refused; 94/108 (87%) achieved a remission; 12 (11%) died early and 2 abandoned. The 5-year overall survival and event-free survival are 61.8% and 55.5% for all patients, 51.7% and 43.6% for first protocol, 68.4% and 63.9% for second one. Baseline WBC count was a risk factor for induction mortality; early hemorrhagic death remains a major cause of failure. ATRA extended consolidation improved results.
... 12 To avoid the possible adverse effects of ATRA in the pediatric population, studies have been carried out in which treatment protocols are applied that include doses of ATRA lower than the conventional dose. Park et al. 15 conducted a study with 76 patients under 18 years of age, 67.1% of them were administered the conventional dose of 45 mg / m 2 / d and the remaining 32.9% received a low dose of 25 mg / m 2 / day. They observed that the incidence rate of RA Syndrome was higher in patients who received the conventional dose (64.7%) and for patients who received a low dose the incidence of the syndrome decreased to 36%. ...
... They found no statistically significant differences between the rates of complete remission, the relapse rates, and the survival rates of both groups. 15 ...
... Park et al. 15 conducted a retrospective investigation in which they found a 9.9% incidence of APL among a total of 801 patients under 18 years of age who were diagnosed with AML in 16 tertiary care medical centers in Korea, during the period between January 2009 and December 2016. In this case, the median age at diagnosis was 10.6 years. ...
Acute promyelocytic leukemia (APL) has shown differences in incidence around the world, it has a characteristic molecular, pathogenic and clinical development mechanism. Despite being a low incidence acute myeloid leukemia (AML) compared to other AML and having a good response to therapy, it continues to be of interest due to the toxicities of its current treatment, to mutations that have shown resistance to those drugs, and to the few possibilities of alternative treatment with all-trans retinoic acid (ATRA) and anthracyclines in the pediatric population. Furthermore, the description of new mutations that originate APL produced by LPA generates new interest in studies that may shed light on their effects on the disease’s incidence, prognoses, and response to treatment. This article aims to review different studies that describe findings of APL in terms of incidences, treatments, side effects, survival, especially in the pediatric population. Different studies propose the use of ATRA - arsenic trioxide (ATO) as the first line of treatment, however, few have been carried out in the pediatric population and the use of ATO is not recommended in children under 5 years of age. On the other hand, the differentiation syndrome (DS) has been d
In Asia, a few countries have a long and established history of collaborative clinical trials successfully formed national children's cancer study groups, but many still do not have such groups. The process of forming national children's cancer groups is fraught with many hurdles, which varies among the countries. One of the basic requirements for running clinical trials is an affordable health care system in which most of the children with cancer can receive the proposed treatment. The health insurance coverage for children with cancer varies from <20% to as high as 100% among Asian countries, and the operation of clinical trials must also be adjusted accordingly. Shortage of research personnel is common, including medical, nursing, research coordinators, and data managers. The establishment of the Asian Pediatric Hematology and Oncology Group aims to provide a good platform for promotion of international clinical trials in the Asian countries.
Background
Accumulating evidence suggests that polo-like kinase 3 (PLK3) plays an essential role in tumor cells and induces cell proliferation and may have implications for the prognosis of various cancers. We sought to define the role of PLK3-dependent proneural–mesenchymal transition (PMT) in the glioblastoma (GBM) therapy.Methods and resultsWe analyzed the expression data for PLK3 by using the TCGA database. PLK3 expression in GBM cell lines was determined by qRT-PCR and Western blotting. PLK3 levels were modulated using Lentivirus infection, and the effects on symptoms, tumor volume, and survival in mice intracranial xenograft models were determined. Irradiation (IR) was performed to induce PMT. PLK3 expression was significantly elevated in mesenchymal subtype GBM and promoted tumor proliferation in GBM. Additionally enriched PLK3 expression could be associated with poor prognosis in GBM patients compared with those who have lower PLK3 expression. Mechanically, PLK3-dependent PMT induced radioresistance in GBM cells via transcriptional regulation of complement C5a receptor 1 (C5AR1). In therapeutic experiments conducted in vitro, targeting PLK3 by using small molecule inhibitor decreased tumor growth and radioresistance of GBM cells both in vitro and in vivo.ConclusionsPLK3-C5AR1 axis induced PMT thus enhanced radioresistance in GBM and could become a novel potential therapeutic target for GBM.
