Background Children undergoing allo-HCT are at high risk of EBV-related complications. The objective of the study was to analyze the impact of prophylactic post-transplant rituximab on EBV infection ...and EBV-PTLD in children after allo-HCT, to determine the risk factors for the development of EBV infection and EBV-PTLD and to determine their outcomes. Additionally, the impact of EBV-driven complications on transplant outcomes was analyzed. Methods Single center retrospective analysis of EBV-related complications in pediatric population undergoing allo-HCT, based on strategy of prophylaxis with rituximab. Overall 276 consecutive children, including 122 on prophylaxis, were analyzed for EBV-driven complications and transplant outcomes. Results Prophylaxis with rituximab resulted in significant reduction of EBV infection (from 35.1% to 20.5%; HR=2.7; p<0.0001), and EBV-PTLD (from 13.0% to 3.3%; HR=0.23; p=0.0045). A trend for improved survival was also observed (HR=0.66; p=0.068), while non-relapse mortality was comparable in both cohorts. The peak value of viral load was a risk factor in the development of EBV-PTLD: 10-fold higher peak viral load in comparison to the baseline 10 4 copies/mL, caused a 3-fold (HR=3.36; p<0.001) increase in the risk of EBV-PTLD. Rituximab treatment was effective as a preemptive therapy in 91.1%, and in 70.9% in EBV-PTLD. Patients who developed PTLD had dismal 5-year overall survival (29% vs 60%; p<0.001), and an increased risk of relapse (72% vs 35%; p=0.024). Conclusions Rituximab for prophylaxis of EBV infection and EBV-PTLD was highly effective in pediatric population. Treatment of EBV-PTLD was successful in 70%, however the occurrence of EBV-PTLD was associated with an increased risk of relapse of primary malignant disease.
Iron overload (IO) is a common and life-threatening complication resulting from the therapy of AL and HCT patients. This study aimed to evaluate the prognostic value of 12 serum biomarkers of iron ...metabolism in pediatric patients treated for AL or undergoing HCT.
Overall, 50 patients with AL after intensive treatment and 32 patients after HCT were prospectively included in the study. AL patients at diagnosis and healthy controls served as reference groups.
The impact of the following 12 serum iron metabolism parameters on the outcome of AL/HCT patients was analyzed: iron, transferrin (Tf), total iron-binding capacity (TIBC), ferritin, ferritin heavy chains (FTH1), ferritin light chains (FTL), hepcidin, soluble hemojuvelin (sHJV), soluble ferroportin-1 (sFPN1), erythroferrone (ERFE), erythropoietin (EPO), and soluble transferrin receptor (sTfR).
With a median follow-up of 2.2 years, high levels of ferritin and low levels of sHJV had an adverse prognostic impact on OS and EFS in children after HCT. If these patients were combined with those with AL after intensive chemotherapy, the results were confirmed for OS and EFS both for ferritin and sHJV.
Among the 12 analyzed serum parameters of iron metabolism, increased levels of ferritin and decreased levels of sHJV had an adverse prognostic impact on survival in children after HCT. More data are needed to clarify the relationship between ferritin, sHJV, and mortality of AL children after intensive chemotherapy, and more extensive prospective studies are required to prove sHJV predictivity.
Although isolated central nervous system (CNS) relapses are rare, they may become a serious clinical problem in intensively treated patients with high-risk neuroblastoma (NBL). The aim of this study ...is the presentation and assessment of the incidence and clinical course of isolated CNS relapses. Retrospective analysis involved 848 NBL patients treated from 2001 to 2019 at 8 centres of the Polish Paediatric Solid Tumours Study Group (PPSTSG). Group characteristics at diagnosis, treatment and patterns of relapse were analysed. Observation was completed in December 2020. We analysed 286 high risk patients, including 16 infants. Isolated CNS relapse, defined as the presence of a tumour in brain parenchyma or leptomeningeal involvement, was found in 13 patients (4.5%; 8.4% of all relapses), all of whom were stage 4 at diagnosis. Isolated CNS relapses seem to be more common in young patients with stage 4 MYCN amplified NBL, and in this group they may occur early during first line therapy. The only or the first symptom may be bleeding into the CNS, especially in younger children, even without a clear relapse picture on imaging, or the relapse may be clinically asymptomatic and found during routine screening. Although the incidence of isolated CNS relapses is not statistically significantly higher in patients after immunotherapy, their occurrence should be carefully monitored, especially in intensively treated infants, with potential disruption of the brain-blood barrier.
Therapy results in pediatric Hodgkin lymphoma reflect remarkable progress in pediatric oncology. In the last decade, relevant development of new therapeutic options for children with refractory or ...relapsed disease has been made. In this study, we retrospectively analyzed therapy results and risk factors in children treated in a single oncology center according to five therapeutic protocols. Data from 114 children treated by a single institution between 1997 and 2022 were analyzed. Classic Hodgkin lymphoma therapy results were divided into four therapeutic periods: 1997–2009, 2009–2014, 2014–2019, and 2019–2022. For nodular lymphocyte-predominant Hodgkin lymphoma, data from one therapeutic protocol was analyzed. For the entire group, the 5-year probability of overall survival was 93.5%. There were no statistically significant differences between therapeutic periods. The occurrence of B symptoms at diagnosis and incidence of relapse were risk factors for death (
p
= 0.018 and
p
< 0.001). Relapse occurred in 5 cases. The 5-year probability of relapse-free survival for the entire group was 95.2%, without significant differences between groups. Patients treated between 1997 and 2009 had over a sixfold higher risk for events, defined as primary progression, relapse, death, or incidence of secondary malignancies (OR = 6.25,
p
= 0.086). The 5-year probability of event-free survival for all patients was 91.3%. Five patients died, and the most common cause of death was relapse. Modern therapeutic protocols in pediatric Hodgkin lymphoma are marked by excellent outcomes. Patients with disease relapses have a notably high risk of death, and the development of new therapeutic options for this group remains one of the main goals of current trials.
A retrospective analysis was performed to investigate the survival outcomes in pediatric acute lymphoblastic leukemia (ALL) based on time period. We hypothesized that improvement has been obtained ...with the time-dependent therapeutic era and rise in the gross domestic product (GDP) and Human Development Index (HDI).
Data from 710 children who were treated for ALL between 1958 and 2018 at a single pediatric center were analyzed for probability of 5-year overall survival (pOS), event-free survival (pEFS) and relapse risk (pRR). Time periods were defined by the treatment protocols used in seven consecutive therapeutic eras.
Over the 60-year period analyzed, pOS increased from 1.2% to 90.7%, pEFS from 1.2% to 86.6%, and pRR decreased from 98.8% to 9.9% for patients treated in the past decade. Risk of mortality for patients who received chemotherapy and hematopoietic cell transplant was reduced to 9.9% in the recent era, however, no statistically significant survival difference was found between patients treated with stem cell transplant and those not.
The therapeutic era, related to improved GDP and HDI, was a statistically significant predictor of increased OS from ALL.
Background:
Amplification of the
MYCN
oncogene is the most unfavorable genetic factor in neuroblastoma patients. However, knowledge about the clinical impact of low-level multiplication of
MYCN
is ...still insufficient. Therefore, we aimed to investigate the disease course in patients with different copy number status of
MYCN
.
Materials and Methods:
We examined 105 children diagnosed with neuroblastoma from 2010 to 2018 in five pediatric oncology centers in Poland. We determined the
MYCN
status at diagnosis by the interphase FISH examination and assessed the clinical outcome in patients.
Results:
A total of 35% of tumors presented with chromosome 2 numerical changes, 20% had
MYCN
amplification and 16% revealed 2p gain. Unexpectedly, we observed very low overall survival and event free survival (EFS) rates in neuroblastomas with 2p gain, which were comparable with patients with
MYCN
amplification.
Conclusions:
The 2p gain alteration should be reported as a strong unfavorable prognostic marker in neuroblastoma patients.
Abstract Background Pelvic Ewing sarcoma (ES) is commonly associated with a worse prognosis. Large size and location limit local control options to radiation therapy, and local recurrences are ...common. We evaluated the impact of hemipelvectomy and radiation on outcomes, including function. Materials and methods Thirty-nine patients (median age 13.5 years) with ES of the pelvis and sacral bones were treated during the period 2000–2012. Fifteen were treated with definitive radiotherapy (RT), 9 patients underwent hemipelvectomy alone, and 15 were treated with combined hemipelvectomy and RT. Results Twenty patients (51.2%) are alive with a median follow-up 3.2 years from diagnosis. Median time from diagnosis to relapse was 1.3 years. Three-year estimates of EFS and OS were 47% and 61%, respectively. Patients treated with surgery or surgery with RT had better outcome than patients treated with RT only (3-year OS 78% or 81% vs . 36%, respectively, p = 0.00083). The outcome of patients with pelvic ES treated with hemipelvectomy was not significantly different from the outcome of all patients with Ewing sarcoma treated on the national Polish protocol. Conclusions Internal hemipelvectomy offers good chances of cure for patients with pelvic ES, with a reasonable rate of complications and good function.
Background Advances in multidisciplinary care for pediatric cancer have resulted in significant improvement in cure rates over the last decades; however, these advances have not been uniform across ...all age groups. Cancer is an important cause of perinatal mortality, yet the full spectrum of malignant neoplasms in newborns is not well defined. Methods The authors have reviewed the clinical features and outcomes of 37 newborns with congenital malignant tumors treated at three referral centers in North, Central, and South Poland between 1980 and 2014. Event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan–Meier methods and compared using long-rank test and Cox models. Results Twenty-two patients were diagnosed prenatally. The most common diagnoses were neuroblastoma (48.7%), followed by malignant germ-cell tumor (16.2%), and Wilms' tumor (8.1%). Neuroblastoma was the most common malignancy among full-term infants, and malignant sacrococcygeal teratoma was the most common malignancy in premature infants. Thirty patients (81%) are alive with a median follow-up of 4.8 years from diagnosis. Patients with Wilms' tumor and malignant germ-cell tumors had the best outcomes (5-year OS 100% for both), whereas the worst prognosis was observed for sarcoma patients (5-year OS 72.92%). Premature infants had better outcome than full-term infants (5-year OS 92.8% vs. 72.58%, respectively). Conclusion Although rare, neonatal cancers can present with an aggressive clinical behavior, but they have a generally good outcome. Early diagnosis and management by expert multidisciplinary teams that integrate perinatal medicine experts with pediatric and surgical oncologists are critical. Centralized care with clear referral pathways that facilitate early initiation of specialized treatment should be prioritized.
Drug resistance and the gene expression profiles might discriminate the therapy outcome, and indicate the subgroup of patients with poor prognosis. In this study we analyzed the gene expression ...profile in correlation with the profile of ex vivo resistance to etoposide in children with acute leukemias.
The ex vivo drug resistance profile was determined by the MTT cytotoxicity assay performed on leukemic blasts of 56 patients. Gene expression profiles were obtained from the results of hybridization of cRNA to Human Genome U133A 2.0 ologonucleotide arrays. The following analyses were performed: correlation analysis, hierarchical clustering, the assignment of location and function. Verification of data for four selected genes (MNDA, GH1, NUDT21, RHOG) was performed by quantitative real time polymerase chain reaction in the studied population and in an independent group of 54 leukemic patients.
Using the permutation Spearman correlation test, a set of 233 probes/209 genes was selected. The global test confirmed the significance of the correlation of gene expression profile and resistance to etoposide (p<0.001). The NUDT21 (nudix, nucleoside diphosphate linked moiety X-type, motif 21) gene showed the strongest correlation with resistance to etoposide (FDR<0.0001%).
Profiling of transcriptome may help in assessing the sensitivity to drugs used in chemotherapy. Resistance to etoposide is possibly associated with a change of expression of a large number of biologically important genes that influence several cellular mechanisms.
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