Abstract ▪888▪This icon denotes a clinically relevant abstract
Pediatric acute megakaryoblastic leukemia (AMKL) occurred in 6.6% (84/1271) of the children enrolled to the AML-BFM98 and 2004 studies.
...Despite a similar phenotype in morphology and immunophenotype, AMKL shows a heterogenous cytogenetic distribution (normal karyotype 23%, complex karyotype 21%, t(1;22) 9%; MLL-rearrangement 8%; monosomy 7 5%, trisomy 8 5%; other aberrations 29%).
Mutations of the hematopoietic transcription factor GATA1 have been identified in almost all children suffering myeloid leukemia of Down syndrome (ML-DS). In addition, GATA1 mutations (GATA1mut) could be identified in children with trisomy 21 mosaic.
Here, AMKL without evidence of Down syndrome or Down syndrome mosaic were analyzed for mutations in exon 1, 2 or 3 of the transcription factor GATA1.
Seventy-one children from the AML-BFM Study group (n=51; 2000–2011), the Netherlands (n=10), France (n=3) and Scandinavia (n=7) were included.
Within the AML-BFM Group the 51 analyzed patients showed similar characteristics compared to the total cohort of 84 children with AMKL of the AML-BFM 98 and 2004 studies.
AMKL was confirmed according to the WHO classification by genetics (t(1;22)); morphology and immunophenotyping. Table 1a) summarizes the patientxs characteristics and b) the cytogenetic results.
For GATA1 mutation screening genomic DNA was amplified by PCR reaction for exon 1, 2, and 3. PCR amplicons were analyzed by direct sequencing or following denaturing high-performance liquid chromatography (WAVE).
Seven different GATA1 mutations were detected in 8 children (11.1%; table 2).
In all GATA1mut leukemia, a trisomy 21 within the leukemic blasts could be detected.
Seven out of these 8 children and all other 64 AMKL patients have been treated with intensive chemotherapy regimens according the study group protocols. The results are given in table 2. All achieved continuous complete remission (CCR; 0.4 to 4.2 years). Display omitted
In one newborn with typical morphology and immunophenotype a GATA1mut associated transient leukemia was supposed. The child achieved CCR (follow-up 6 years).
In total, allogeneic stem cell transplantation in 1st CR was performed in 6 children with AMKL (GATA1mut leukemia n=1). Display omitted
GATA1 mutations occurred in 11% of children with AMKL without any symptoms or evidence of trisomy 21 or trisomy 21 mosaic. GATA1 mutations are associated with a trisomy 21 within the leukemic blasts. Although non-response occurred, prognosis was significant better compared to other AMKL. Therefore, analysis of GATA1 mutation in infant AMKL is strongly recommended. Whether treatment reduction similar to ML-DS Down syndrome is feasible needs to be confirmed.
No relevant conflicts of interest to declare.
is a relatively common environmental black yeast with worldwide distribution and is a rare cause of fungal infection, mostly in patients with certain predisposing factors. Due to the rarity of the ...infection, little is known about the specific predisposing factors, way of infection or treatment.
Here, we report what is to our knowledge the first case of
infection in a child after allogeneic stem cell transplantation. We also review all paediatric cases reported in the literature since 1993.
This is, to our knowledge, the first reported case of
infection in a child after allogeneic stem cell transplantation. This report should increase the awareness of
in immunocompromised paediatric patients, particularly after stem cell transplantation.
Abstract 481
Childhood leukemia frequently originates prenatally. Only a small percentage (<1%) of children with recurrent leukemia associated aberrations detected at birth suffer leukemia later on. ...In addition, no option to treat the preleukemic clone is availabel. Therefore, neither general screening at birth is useful nor preemptive treatment is possible.
The high incidence (5 to 10%) of the transient leukemia (TL) in newborns with trisomy 21 and the high risk to develop a myeloid leukemia of Down Syndrome (ML-DS) within the first 4 years of life supported the hypothesis that the elimination of the preleukemic GATA1 positive clone might prevent leukemia. Prerequisites are the high sensitivity of TL-blasts to cytarabine, the recurrence of the same GATA1-mutated clone and the feasibility to monitor the preleukemic clone.
Since 4/2007 69 children with TL were enrolled the study “Prevention of Myeloid Leukemia in Children with Down Syndrome and Transient Leukemia” (EudraCT 2006-002962-20) ; Germany n=50, The Netherlands n=16, Slovakia n=1, Czech Republic n=2).
Inclusion criteria were met by 52 children (study patients), 17 children were observed only (protocol patients). Table 1 summarizes the patients' characteristics. The TL and ML-DS specific mutations of the transcriptions factor GATA1 have been detected in 60 children (87%), failure of detection were caused by low percentage of blasts (<2%) combined with late diagnosis (≥20 days after birth). The median follow-up within the study group was 1 year (0.2 to 2.3 years).
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Totally, 58 % of the children showed clinical symptoms associated to the TL, severe complications have been reported in 22 children (table 2). According to the study guidelines 20 out of these 22 children were treated with low dose cytarabine (1.5mg/kg body weight 1 week).
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Enrollment to the study including reference diagnostics and consulting, and a consequent treatment seems to improve the prognosis of this particular group. Compared to the historical group of children with similar characteristics (Klusmann et al. Blood 111(6):2991-8, 2008), the overall survival (2 years) significantly increased from 55±7% to 84±8%, p=0.03.
MRD diagnostics by qRT-PCR and/or immunophenotyping was performed in 53 children (77%). Reasons for failure were early deaths (n=9; cardiac defects n=1, prematurity/MOV n=7, liver fibrosis n=1), refusal of monitoring by the parents (n=3), lack of material (n=4). If the MRD-level at week 8 and/or 10 exceeded 10-3 (qRT-PCR) or 10-2 (immunophenotyping), respectively, intervention with low-cytarabine was recommended. Currently, 39 children were already analyzed at week 12 (1st endpoint).
In 7 children (13%) treatment recommendation according to high MRD levels were given. With exception of transient myelosuppression (CTC Grade II) no severe side effects occurred. All children but two became MRD negative at week 12. To date one child with persistent detectable MRD levels suffered ML-DS (1 year after TL).
In summary, participating in the study and treatment of children with TL causing severe clinical symptoms seems to improve the prognosis.
Although the recruitment into the study is faster than expected and the results to date are promising, the follow-up is much too short to draw definitive conclusion.
No relevant conflicts of interest to declare.
Abstract
BACKGROUND
Low grade gliomas (LGG) are the most frequent tumors of the central nervous system in children. Pediatric LGG are a heterogeneous set of tumors. They encompass tumors of ...astrocytic, oligodendroglial, and mixed glial-neuronal histology, and are classified according to the World Health Organization (WHO).
METHODS
The objective of our study was to analyze the outcome of patients with LGG from the Department of Pediatric Hematology and Oncology in Bratislava, Slovakia treated in period from January 2000 up to December 2015. The cohort consisted of 139 patients with LGG, 83 boys/56 girls.
RESULTS
The most common histological type was pilocytic astrocytoma (WHO grade I) in 64 children. Primary surgery was performed in 102 children and 72 from these do not need any further therapy. Forty eight patients received chemotherapy first or other line therapy.
Radiotherapy was used 26 times. In our study median follow up was 82,3 months and overall survival for the whole cohort was 97,2%.
CONCLUSION
In pediatric low grade glioma surgery is the mainstay of therapy. Ten year overall survival rates for patients whose tumors are completely resected are 90% or greater. Chemotherapy is reserved for progressive or recurrent tumors. Radiotherapy can also improve OS but is associated with more frequent adverse effects. Recent advent of integrated genomics and NGS has implicated the activation of RAS/RAF/MEK pathway in tumor genesis of LGG. Many of these biological advances are changing treatment paradigma, particularly in low-grade gliomas, where rationale targeted therapies are currently being explored in clinical trials.
Súhrn: Bolesti brucha patria medzi pomerne časté symptómy u adolescentov. Príčiny, ktoré sa podieľajú na bolestiach brucha, sú pestré a tým aj diferenciálna diagnostika je pomerne rozsiahla a ...zložitá. To súvisí pravdepodobne s tým, že brucho zaberá pomerne veľkú oblasť, obsahuje množstvo orgánov, štruktúr, systémov vrátane lymfatických uzlín, ktoré generalizovane reagujú na infekciu, či nádorové ochorenia. V našej kazuistike opisujeme prípad 17-ročného pacienta s náhlymi bolesťami brucha, chudnutím, vracaním a ikterom. V rámci diferenciálnej diagnostiky sa realizovali laboratórne a zobrazovacie vyšetrenia so zameraním na pankreas a hepatobiliárny trakt, kde sa zobrazila zväčšená hlava a chvost pankreasu, peripankreatická lymfadenopatia s vedľajším nálezom drobných ložísk na obličkách. V úvode sa suponovala skôr hereditárna pankreatitída a pseudotumory na obličkách, vzhľadom na vek pacienta bol menej pravdepodobný tumor pankreasu a metastázy. Definitívna diagnóza bola stanovená odberom bioptických vzoriek pankreasu pomocou endosonografického vyšetrenia. Histologický a cytologický nález preukázal prítomnosť lymfocytárnych blastických buniek, charakteru CD20+ B-NHL, konštatovaný difúzny veľkobunkový B-lymfóm pankreasu (DLBCL – diffuse large B cell lymphoma). Staging ochorenia nepreukázal inflitráciu malígnych buniek v kostnej dreni a centrálnej nervovej sústave. Promptne stanovená diagnóza a podaná príslušná onkologická liečba (chemoterapia v kombinácii s monoklonálnou protilátkou) zabezpečila pacientovi návrat do každodenného života a je nevyhnutným predpokladom priaznivej prognózy pacienta. Kľúčové slová: bolesti brucha – žltačka – difúzny veľkobunkový B-lymfóm
Background
Acute myeloid leukemia (AML) in children is rare, and it is generally considered to be more resistant to chemotherapy than acute lymphoblastic leukemia. However, because of the gradual ...intensification of chemotherapy and better supportive care, outcomes have improved considerably over the past 20 years. The management of children with AML in the Slovak Republic was unified and centralized during the second half of the 1990s with the introduction of Berlin-Frankfurt-Munster (BFM) protocols. In 2000, the AML-BFM-1998 protocol was introduced, and data collection became centralized.
Methods and results
Between 2000 and 2009, 73 patients (f = 38, m = 35) were treated according to the AML-BFM 1998. Complete remission (CR) was achieved in 89 % of the patients. The 5-year event-free-survival (EFS) and overall survival rates were 47 ± 6 % and 52 ± 6 %, respectively. The cumulative incidence of relapse was 38 %. The early death (ED) rate and the death rate in CR were both 7 %. The prognosis of children with favorable cytogenetics (standard risk (SR) group) tended to be better than the high-risk group (all other patients; EFS 63 vs. 40 %,
p
= 0.15). This tendency was supported by a significantly lower cumulative incidence of relapse in the SR-group (
p
= 0.008 by the log-rank test).
Conclusion
Unified treatment protocols and centralized diagnostics improved the management of pediatric AML in the Slovak Republic and increased the overall survival rate to 52 % in the total group and 68 % in children with a favorable cytogenetics. The high relapse rate and treatment-related mortality will be reduced by improving diagnostics, disease control, and the management of treatment-related complications.
The first event in origination of many childhood leukemias is a specific preleukemic fusion gene (PFG) that arises, often in utero, in hematopoietic stem/progenitor cells (HSPC) from misrepaired DNA ...double strand break (DSB). An immanently elevated level of DSB and impaired apoptosis may contribute to origination and persistence of PFG and donor cell-derived leukemia in recipients of allogeneic transplantation of umbilical cord blood (UCB). We investigated DSB, apoptosis and PFG in the backtracked UCB cells of leukemic patients. RNA from UCB of three patients with acute lymphoblastic leukemia, patient with acute megakaryoblastic leukemia and Down syndrome, and four healthy children was screened for common PFG by RT-qPCR. Presence of PFG was validated by sequencing. Endogenous γH2AX and 53BP1 DNA repair foci, cell populations, and apoptosis were analyzed in UCB CD34+/- cells with imaging and standard flow cytometry. We found
and
fusion genes in UCB of two out from four pediatric patients, apparently not detected at diagnosis, while UCB cells of
ALL patient were tested negative for this PFG and no PFG were detected in UCB cells of healthy children. No significant difference in DNA damage and apoptosis between UCB CD34+/- cells from healthy children and leukemic patients was observed, while Down syndrome trisomy increased DNA damage and resulted in distribution of cell populations resembling transient abnormal myelopoiesis. Our findings indicate increased genetic instability in UCB HSPC of leukemic patients and may be potentially used for diagnostics and exclusion of possibly affected UCB from transplantation.
Invasive fungal infections are a life-threatening complication of cancer treatments, especially in hemato-oncological patients. Mucormycosis is the third leading cause of invasive fungal infections ...after Aspergillus and Candida infections. The first clinical symptoms are usually non-specific, which can lead to a late diagnosis and delayed therapy.
The objective of this report is to summarize data in the literature about mucormycosis and to present a case report of a patient with acute lymphoblastic leukemia, who developed this infection at our center. Risk factors for the development of mucormycosis, clinical symptoms, radiology, laboratory results, and outcome were retrospectively evaluated.
We describe a 6-years-old female patient with acute lymphoblastic leukemia. During the induction phase of therapy, the patient developed febrile neutropenia and did not respond to therapy with a combination of antibiotics and supportive treatment. Pansinusitis and orbitocellulitis developed. Examination of the biological material revealed that the etiological agent was a Rhizopus sp. The patient was treated with a combination of antimycotic drugs, but the infection disseminated to the central nervous system. She underwent radical surgical resection of the affected tissue. At this time, she is still under treatment with antimycotic and oncology agents, but is in remission of the main diagnosis and in good clinical condition.
Mucormycosis is an invasive fungal infection with high morbidity and mortality. Early diagnosis and initiation of effective therapy using a combination of amphotericin B administration and surgery are necessary to obtain a favorable outcome. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Pediatric oncologists are often faced with situations in which parents or guardians refuse recommended treatment for curable childhood cancer. Deciding how to proceed in such situations is an ethical ...dilemma. The aim of this article is to consider optimal approaches when parents are strongly against oncological treatment, potentially compromising their childrens rights for health care and to the chance for cure.
In this paper, we report two cases of treatment refusal from our department and the impact of such decisions on the children themselves. Case no. 1 describes a child with retinoblastoma whose parents refused standard treatment in order to seek alternative treatment abroad. Case no. 2 describes a patient with a primary lymphoma of bone who received treatment by a court order after parental refusal.
When parents refuse a treatment for potentially curable cancer, the medical team often focuses on the certainty of death without treatment. In the background, there is a smaller but still significant risk that - even if the treatment is eventually accepted or compelled - the child will still die from treatment-related complications or refractory disease, possibly with considerable suffering. The reasons for refusing a treatment vary. The entire medical team is tasked with trying to respectfully understand the reasoning behind the parents unwillingness to accept the treatment, in order to address all possible misunderstandings and to propose solutions that could be acceptable for the parents. In some situations however, it is necessary to resolve the dilemma by legal means in order to protect the life of the child.Key words: oncology - ethics - decision making - treatment refusal - legal guardians The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 7. 8. 2017Accepted: 7. 9. 2017.
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