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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 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.

Introduction: We analyzed the epidemiology and outcomes of treatment of invasive fungal disease (IFD) in children during anticancer therapy (PHO, pediatric hematology and oncology) or after hematopoietic cell transplantation (HCT) over a period of eight consecutive years in a single-center study. Material and methods: Overall, a total of 254 HCTs were performed, and 415 children were newly diagnosed for malignancy. Incidence, epidemiology and outcome of IFD were analyzed. Results: The cumulative incidence of any IFD was 32.6% in allo-HCT, 22.2% in PHO, and 6.0% in auto-HCT patients. The incidence of proven +probable IFD was 12.6%, 10.4%, and 6.0%, respectively. As many as 77.0% HCT and 67.4% PHO of fungal episodes occurred in acute leukemia patients: the highest incidence of any IFD was observed for acute lymphoblastic leukemia (29.3% in HCT; 40.5% in PHO) and for acute myeloblastic leukemia (51.1% in HCT; 65.0% in PHO) patients. There were no significant differences in the incidence of fungal infections in both allo-HCT and PHO patients between the 2-year periods. Factors contributing to an increased risk of IFD in allo-HCT patients were: CMV replication, and acute and chronic graft-versus-host disease (GvHD). Survival from IFD was 91.9% in PHO, and 78.1% in HCT patients. Fungal pneumonia in HCT patients resolved in 62.9%, while in PHO patients it resolved in 93.5%. Conclusions: The risk of IFD in allo-HCT patients is much higher than in auto-HSCT and PHO patients. The outcome of IFD is better in PHO and auto-HCT than in allo-HCT settings.

This is a review of the therapeutic options for resistant/refractory post-transplant lymphoproliferative disorder (PTLD) in relation to Chimeric antigen receptor-T cell (CAR-T) therapy. Out of a number of possible future strategies for the treatment of PTLD, the following methods were implemented in real-world practice: anti-PD1 therapy with checkpoint inhibitor nivolumab, new anti-CD20 ofatumumab, brentuximab vedotin, and zanubrutinib. However, for all these innovative methods, only individual cases of successful treatment of rituximab-resistant Epstein-Barr Virus (EBV)-PTLD patients have been reported so far. CAR-T is an innovative method of treatment, based on genetic modification of receptors of T autologous lymphocytes, creating the "living drug". This therapy can be potent against resistant PTLD, which is a lymphoproliferation of B-lymphocytes. The published real-world data of 17 patients treated with CAR-T for PTLD indicate a success rate of 76.5%. There is development of innovative methods of treatment of resistant/refractory PTLD, with high rate of resolution after CAR-T therapy.

Background/Aim: Comparison of transplant outcomes in long-term follow-up of children after total body irradiation (TBI)- or chemotherapy-based conditioning allogeneic hematopoietic cell transplantation (allo-HCT). Patients and Methods: Patients undergoing allo-HCT for Acute lymphoblastic leukemia (ALL) conditioned either with TBI (n=55) or chemotherapy (n=84) were compared. The following transplant outcomes were analyzed: overall survival (OS), event-free survival (EFS), relapse incidence (RI), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS). Results: All analyzed long-term transplant outcomes were significantly better for patients conditioned with TBI at 2 years after transplant. OS at 2 years was 84% after TBI and 60.5% after chemotherapy-conditioning (p=0.005). Risk factor analysis showed that two factors, TBI-based conditioning and transplant in first remission of ALL, significantly improved OS, EFS, GRFS, and decreased RI. Conclusion: TBI-based conditioning before allogeneic HCT in children with acute lymphoblastic leukemia provides significantly better transplant outcomes, when compared to chemotherapy-based conditioning.

BackgroundThrombopoietin receptor agonists have been repeatedly confirmed to be safe, efficient, and well tolerated in pediatric patients with chronic immune thrombocytopenia (cITP).Material and methodsIn this report, we present data summarizing the Polish experience of the use of eltrombopag in cITP patients, refractory to standard first-line care. Our analysis was based on clinical and epidemiological data from the Nationwide Therapeutic Program 2018–2020. Quality of the response to the eltrombopag treatment was defined according to the International Consensus Guidelines as follows: complete response (CR) defined as platelet count (PLT) ≥100 × 109/L and absence of bleeding; response (R) defined as PLT ≥30 × 109/L and at least two-fold increase in the baseline count and absence of bleeding.ResultsWe evaluated 60 patients (33 boys and 27 girls) with chronic and refractory ITP. Median age at beginning of treatment was 9.5 years. Median PLT at the first eltrombopag administration was 30 × 109/L. The median follow-up was 7 months (range, 3–22 months). After 1 week of treatment, response (R) was noted in 53.3% (95% confidence interval [CI]: 40.7%–66.0%) patients, and complete response (CR) was seen in 21.6% (95% CI: 11.2%–32.1%). We evaluated the long-term duration of the response and found that it was obtained in 84.4% (95% CI: 71.8%–97.0%) and 88.9% (95% CI: 77.0%–100%) of patients after 6 and 12 months, respectively, of eltrombopag therapy, while CR was reached, respectively, in 46.9% (95% CI: 29.6%–64.2%) and 29.6% (95% CI: 12.4%–46.9%) patients. No serious adverse events were reported.ConclusionOur data support the safety and efficacy of eltrombopag use in cITP pediatric patients.

Background Oral mucositis (OM) is considered to be one of the worst and most debilitating complications of conditioning for hematopoietic cell transplantation (HCT). Prevention and treatment of this complication is one of the utmost priorities of supportive therapy during transplant procedure. The objective of this study was the analysis of the influence of palifermin, keratinocyte growth factor (KGF), on transplant outcomes in patients undergoing allo-HCT. Patients and methods A total of 253 allo-HCTs performed between 2003-2018 in patients aged 0-19 years at a single center were analyzed. KGF was administered in 161 HCTs. Uni- and multivariate risk factor analyses were performed. Results In spite of reducing the duration and grade of mucositis, no prognostic impact of KGF was shown for overall survival, event-free survival, relapse incidence, acute and chronic graft-versus-host disease (GVHD), nor GVHD-free relapse-free survival. Conclusion Palifermin had no impact on transplant outcomes in children and adolescents undergoing allo-HCT.

IntroductionLeukemia belong to 31% of all childhood malignancies. Acute lymphoblastic leukemia (ALL) is the most frequent type of pediatric leukemia accounting for 80–85% of all cases. Progress in diagnostics and therapy of leukemia is dependent on international cooperation. The objective of the study was the analysis of non-hematological toxicity during intensive chemotherapy according to two consecutive intercontinental protocols.Patients and methodsA total number of 210 children diagnosed for ALL who were treated in single center between 2002 and 2018 were divided in two groups defined by therapeutic protocol: ALL IC-BFM 2002 (group 1) and ALL IC-BFM 2009 (group 2). Data were entered prospectively from 2002 into international ALL IC-BFM 2002 and ALL IC-BFM 2009 registry. Non-hematological toxicity was analyzed according to the criteria followed in protocols, compatible with CTCAE criteria.ResultsThe most frequent toxicities included hepatic toxicity with transaminitis and hyperbilirubinemia, infections, oral mucositis and gut toxicity with vomiting, and/or diarrhea. Non-hematological toxicity episodes calculated as a ratio per patient were comparably often observed in both the groups; however, the distribution was different. There were more grade III and less grade II toxicities. This was mainly related to significant increase in the rates of infections and transaminitis. However, there was a significant decrease in vomiting and central and peripheral neurotoxicity.ConclusionsIntensive treatment of ALL is burdened with frequent severe toxic and infectious complications. Further progress in therapy of pediatric ALL is dependent on sophisticated supportive therapy and very well experienced and knowledgeable therapeutic team.

IntroductionOral mucositis is regarded by patients as one of the worst and debilitating complications of conditioning and hematopoietic cell transplantation (HCT). Prevention of mucositis is one of the priorities of supportive therapy during and after conditioning.ObjectivesThe primary objective of the study was the analysis of efficacy of keratinocyte growth factor (KGF, palifermin) used in prophylaxis of oral mucositis in patients undergoing allo-HCT. The secondary objectives of the study included the analysis of the influence of palifermin on clinical course of oral mucositis and early transplant outcomes, as well as analysis of the contraindications of palifermin in patients undergoing allo-HCT.Patients and methodsA total number of 253 allo-HCT performed between 2003 and 2018 in patients aged 0–19 years in a single center were analyzed. Overall, in 161 HCTs, palifermin was administered.ResultsPatients receiving KGF were transplanted earlier in the context of calendar year, and more often received ATG, mainly due to the higher rate of unrelated donor transplants. Allo-HCT patients who were administered palifermin had shorter time of mucositis (median: 9 vs. 13 days, p < 0.001), lower mucositis grade (median: 2° vs. 3°; p < 0.001), shorter period of total parenteral nutrition (median: 19 vs. 22 days; p = 0.018), and lower incidence of episodes of febrile neutropenia (median: 39.1% vs. 83.1%; p < 0.001).ConclusionsThe use of palifermin has decreased duration and severity of oral mucositis in children after allo-HCT. Palifermin is a safe and well-tolerated compound in children undergoing allo-HCT.

Background 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). Materials and methods 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. Results 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. Conclusion The therapeutic era, related to improved GDP and HDI, was a statistically significant predictor of increased OS from ALL.

Functionalized carbon nanotubes are interesting, promising and unique delivery systems for anticancer drugs, which are now in the spotlight of nanomedicine. Connecting nanotubes with anticancer drugs or new compounds with anticancer properties aims at improving their stability, efficiency and reduces the toxic side effects of cancer treatment. In our research, we are interested in connecting functionalized MWCNTs-NH2 with [InH][trans-RuCl4(In)2], (KP1019) which is one of the most promising anticancer ruthenium(iii) drug candidates, known mainly as a cytotoxic agent for the treatment of platinum-resistant colorectal cancers. As a result of the amidation of MWCNTs (1), MWCNTs-NH2 (2) were obtained. Then, they were modified with [InH][RuCl4(In)2] (4) and the nanosystem [MWCNT-NH3+][RuCl4(In)2-] (3) was obtained. The characterization of the resulting products was performed using IR, Raman spectroscopy, thermal gravimetric, XRD, STEM-EDX, ESI-MS, ICP-MS, and XPS analyses. The cytotoxic activity has been tested on human lung carcinoma (A549), chronic myelogenous leukemia (K562) and human cervix carcinoma (HeLa) cells which showed the higher toxicity of the nanosystem than the ruthenium complex.

Background A complex multifactorial dysregulation of immune system, including cytokines and autoantibodies production, and also proteins modification underlay the primary mechanism of immune thrombocytopenia (ITP). Specific genetic profile of ITP patients is presumed, especially those with a long and complex natural history of the disease. Aim of the study Gene expression analysis of VNN1 and PPARγ in children with immune thrombocytopenia. Materials and methods Candidate genes were identified with microarray cDNA procedure. For the validation of VNN1 and PPARγ expression changes we used qRT-PCR performed comparatively in samples of newly diagnosed ITP (ndITP, n = 16), chronic ITP (cITP, n = 8) and patients without thrombocytopenia (n = 5). Results We analyzed the data of patients, followed for at least 12 months after ITP diagnosis. No significant differences of VNN1 expression profile were found in between groups (p > 0.05). Lower signatures of mean PPARγ normalized expression values were noticed in chronic ITP patients in contrast to newly diagnosed ITP subjects (p = 0.009). Differences between VNN1/PPARγ ratio values found in ndITP group comparing to subjects with progression to cITP were close to statistical significance (p = 0.054). Conclusions Analysis of the VNN1 and PPARγ expression profiles utility in children diagnosed with ITP requires further investigation.

Background Primary immune thrombocytopenia (ITP) is one of the most common hematologic disorders in pediatric population. In 2009 the new unified terminology regarding: definition, clinical classification of the disease and response to treatment was proposed. The main study objective was the comparative analysis of clinical aspects of primary ITP in children regarding the contemporary definitions and historical criteria. Methods Data were collected through medical chart review of subjects identified from hospitalization records (Pediatrics, Hematology and Oncology Department) from the period of 2002–2011. Results Data of 209 subjects were analyzed. According to recent definitions 206/209 patients (98.6%) could be defined. Using the historical criteria 86.12% were classified as acute and 13.88% as chronic ITP. Newly diagnosed primary immune thrombocytopenia was confirmed in 166/206 cases, persistent ITP in 20/206, and chronic ITP in 20/206 of subjects. Depending on applied criteria we noticed significant differences in acute ITP patient number. Regardless of adjusted definitions, the response rates were higher among treated patients (p Conclusions Contemporary definitions allow for more adequate categorization on most of the patients with primary immune thrombocytopenia considering the specific clinical aspects and different natural history of primary ITP in children.

This report presents the case of a 15-year-old male with severe chronic neutropenia, leukopenia, and persistent tetraploid mosaicism in the bone marrow and peripheral blood. His father had mild neutropenia and bone marrow tetraploidy. Flow cytometric analysis of DNA content peripheral blood showed tetraploidy in 20% of granulocytes and 15% of monocytes. Sequence analysis of the ELA2 gene was normal, but the GFI1 gene exhibited transient appearance of single base changes the coding region and promoter. We speculate that an underlying genetic defect, inherited in an autosomal dominant pattern, leads to both disordered mitosis and neutropenia in this kindred. Pediatr Blood Cancer 2008;50:630–632. © 2006 Wiley-Liss, Inc.