Nodular lymphocyte predominant Hodgkin lymphoma: Experience of Polish Pediatric Leukemia/Lymphoma Study Group.

Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) is a rare clinical entity. To investigate NLPHL clinical course and treatment a survey was performed within Polish Pediatric Leukaemia/Lymphoma Study Group (PPLLSG) participating centers. A questionnaire was sent to all participating centers and analysis of clinical data was performed. From 2010 to 2019, 19 pediatric patients with confirmed NLPHL were registered in Poland. Median age of patients was 12.2 (5.5 - 17.8) years. NLPHL occurred mainly in males (n = 17). Most of the patients (n = 16) had early stage disease - Stage I (n = 6) and stage II (n = 10). Four of the six patients with stage I disease (I A, n = 5; I B, n = 1) underwent complete primary resection. One of these relapsed and was treated with CVP (cyclophosphamide, vinblastine, prednisone) chemotherapy. Two other patients who were not resected completely received CVP chemotherapy and no relapses were observed. Thirteen patients presented with unresectable disease. Of these, eight received three CVP chemotherapy cycles, and five were treated with other chemotherapy regimens. Three relapses were observed and these patients were further treated with chemotherapy and rituximab. One patient underwent autologous stem cell transplantation (auto-SCT). All patients remain alive. Five-year progression-free survival and overall survival for the entire group of patients was 81.6% and 100%, respectively. NLPHL treatment results are consistent with results noted in other countries. Early stage patients have very good outcomes with surgery and observation or low intensity chemotherapy, but this approach may be insufficient in advanced disease.

Plerixafor combined with G-CSF for stem cell mobilization in children qualified for autologous transplantation- single center experience.

Failure of autologous peripheral blood CD34+ stem cells collection can adversely affect the treatment modality for patients with hematological and nonhematological malignant diseases where high dose chemotherapy followed by hematopoietic stem cell transplantation has become part of their treatment. Plerixafor in conjunction with G-CSF is approved for clinical use as a mobilization agent. The clinical efficacy of Plerixafor in CD34+ cells collection was analyzed in our institution. A total of 13 patients aged 1-15,5 years received Plerixafor in combination with G-CSF: 7 with neuroblastoma, 2 with Ewing's sarcoma and single patients with Hodgkin's lymphoma, germ cell tumor, retinoblastoma and Wilms tumor. Twelve patients (923%) achieved CD34+ cell counts of ≥ 20 × 106/L after 1-7 doses of Plerixafor. The average 9,9 - fold increase in number of CD34+ cells were achieved following the first dose and 429 - fold after second dose of plerixafor. Among the 13 patients, 12 yielded the minimum required cell collection of 2 × 106/kg within an average of 2 doses of Plerixafor. The mean number of apheresis days was 1.75. The median total number of collected CD34+ cells was 982 × 106/kg. Plerixafor enables rapid and effective mobilization, and collection of sufficient number of CD34+ cells.

Health Status in Long-Term Survivors of Hepatoblastoma.

The aim of this study was to evaluate the health status of children cured from hepatoblastoma. Forty-five patients with hepatoblastoma treated between 1996-2014 were assessed. The recorded data included sex, age at diagnosis, disease stage, treatment methods, time since diagnosis, and the evaluation of health status domains which included performance status, growth development, hearing, cardiovascular, skeletal, gastrointestinal, genitourinary, neurological, and hematological function. There were 30 boys and 15 girls. The age at diagnosis ranged from one month to 14 years (median one year). At the time of the health status evaluation, the youngest patient was 5.5 years old and the oldest was 21 years of age (median-10 years). All patients were treated according to the Childhood Liver Tumors Strategy Group-SIOPEL recommendations, though they were not active participants of the studies. The median cumulative dose of cisplatin was 520 mg/m2 and 360 mg/m2 for doxorubicin. Thirty-six patients underwent partial hepatectomy, and nine total hepatectomy and liver transplantation. At a median of nine years from diagnosis, 68% of hepatoblastoma survivors had experienced at least one chronic health condition of any grade. The most frequent late complication was ototoxicity (28.8%), and the most serious were second malignancies (6.6%) and cardiomyopathy (4.4%). Conclusion: Survivors of hepatoblastoma are at risk for long-term complications. They require long-term monitoring for late effects.

Changes in the chemical composition of mineralised teeth in children after antineoplastic treatment.

INTRODUCTION: Chemotherapy, neoplasms, and their complications linked to malabsorption, malnutrition, and metabolic disorders may lead to improper tooth development and frequent severe caries in patients during/after antineoplastic treatment and to a more frequent improper tooth development in patients undergoing chemotherapy during odontogenesis. However, the causes of these abnormalities remain unknown; there are no studies on the impact of antineoplastic treatment and its complications on the chemical composition of mineralised teeth. AIM OF THE STUDY: To compare the chemical composition of mineralised teeth extracted due to complicated caries in children after chemotherapy, and of teeth extracted due to orthodontic treatment in generally healthy children. MATERIAL AND METHODS: The treatment group included five teeth extracted due to complicated caries in children after antineoplastic treatment. The control group included five teeth extracted due to orthodontic treatment in generally healthy children. The chemical composition of enamel, dentine, cementum, interior of the canal, and enamel abnormalities in teeth extracted from patients after chemotherapy and in generally healthy patients were assessed with energy-dispersive X-ray spectroscopy. Results were analysed statistically. RESULTS: The magnesium (Mg) and zinc (Zn) mass contents in the enamel of patients after chemotherapy increased and so did the calcium (Ca) to phosphorus (P) ratio when compared to controls. Areas with abnormal enamel in patients after chemotherapy had lower concentrations of Ca and P, and higher concentrations of trace elements (Mg, Cl, and Na). The levels of the assessed elements in dentine, cementum, and inside the canal were similar in both groups of teeth.

Dental Caries in Children and Adolescents During and After Antineoplastic Chemotherapy.

OBJECTIVE: To assess caries incidence, intensity, and treatment in children and adolescents under/after antineoplastic treatment. STUDY DESIGN: Patients with permanent and mixed dentition were divided into three groups of 60 patients each (5-18 years): CH - under chemotherapy; PCH - after chemotherapy; CG - generally healthy subjects. Caries incidence, intensity (DMFT/dmft, DMFS/dmfs), and mean numbers of teeth/surfaces with white spot lesions-WSL (D1+2/d1+2) were assessed following the ICDAS-II criteria. STATISTICAL ANALYSIS: Mann-Whitney U test, significance at p≤0.05). RESULTS: Caries incidence was significantly higher in PCH and CH (88.33% and 90%) than in CG (66.66%). Caries intensity was higher in both mixed and permanent dentition in patients under and after chemotherapy. The DMFS/DMFT correlation was the highest in PCH. Treatment indexes for primary and permanent teeth treatment were significantly lower in PCH and CH than CG. CONCLUSION: Antineoplastic chemotherapy is associated with caries development and its high incidence during/after treatment. As dental hygiene was poor in patients under and after antineoplastic treatment, dental checkups need to be more frequent and thorough.

Factors influencing caries incidence in permanent teeth in children/adolescents under and after anti-neoplastic treatment.

AIM OF THE STUDY: To determine reasons for the increase in caries among children/adolescents treated for neoplasms. MATERIAL AND METHODS: Health promoting behaviour, oral hygiene (PLI), gingiva (GI), dentition (DMFt/DMFs), number of teeth with white spot lesions (WSL), and enamel defects (ED) were assessed in three groups of 60 patients each. The three groups were as follows: under chemotherapy (CH), after chemotherapy (PCH), and generally healthy (CG). Medical files supplied information on neoplasm type, chemotherapeutic type and dose, age at treatment start, chemotherapy duration, and complications. Statistical analysis was performed with Mann-Whitney U test and Spearman's rho test. RESULTS: The age at which chemotherapy was started/its duration was 5.9 ±4.0/1.3 ±0.5 years in PCH and 9.12 ±4.44/0.8 ±0.3 years in CH; PCH completed treatment 4.9 ±3.4 years ago. Chemotherapy most often included vincristine (VCR), etoposide (VP-16), adriamycin (ADM), cyclophosphamide (CTX), cisplatin (CDDP), and ifosphamide (IF). Mucositis occurrence was 28.33% in PCH and 45.00% in CH; vomiting occurrence was 43.33% and 50.00%, respectively. Nutrition and prophylaxis mistakes occurred more often in CH/PCH than in CG; PLI, GI, caries incidence and severity, and the number of teeth with WSL were higher. Correlation between caries incidence and chemotherapeutic type and dose, age at treatment start and treatment duration, mucositis, emesis, PLI, GI, ED, no fluoride prophylaxis, and nutritional mistakes was established. Ifosphamide and mucositis treatment played a major role in chemotherapy; after chemotherapy - ED and CTX, ADM, IF, and VP-16. CONCLUSIONS: Caries in permanent teeth in children/adolescents undergoing chemotherapy result from nutritional mistakes, poor prophylaxis, and indirectly from chemotherapy complications (first mucositis and emesis, and later developmental ED).

Antineoplastic chemotherapy and congenital tooth abnormalities in children and adolescents.

AIM OF THE STUDY: Chemotherapeutic treatment in children and adolescents carries a risk of congenital tooth disorders and dentinoma. Study objective is to assess the correlation between tooth abnormalities, early complications of multidrug chemotherapy, and chemotherapeutics used in different antineoplastic therapies in children and adolescents. MATERIAL AND METHODS: Enamel defects (developmental defects of enamel index - DDE index) and defects in tooth number, size, and structure were assessed clinically and radiologically in 60 patients who underwent chemotherapy on average 4.9 ±3.4 years earlier (PCH), and 60 generally healthy subjects (control group - CG), aged 6-18 years. Höltta's defect index (DeI) was calculated. Medical files provided information on neoplasm type, age at treatment start and chemotherapy duration, chemotherapeutic type and dose, vomiting, and mucositis (CTCAE v4.0). Statistical significance of differences between groups was assessed with the Mann-Whitney U test and the correlation between dental defects and chemotherapy with Spearman's rank correlation coefficient (significance p ≤ 0.05). RESULTS: Enamel defects, tooth agenesis, microdontia, root resorption, taurodontism, and dentinoma occurred statistically significantly more often in the PCH group. A correlation was established between vincristine use and dose and all types of dental defects; cyclophosphamide, doxorubicin, and isophosphamide and hypodontia; microdontia, root resorption, and enamel defects; etoposide and cisplatin and microdontia, root resorption, and enamel defects; methotrexate root resorption and enamel defects; carboplatin and dentinoma and enamel defects. Mucositis and vomiting promoted root resorption, microdontia, and enamel defects. CONCLUSIONS: Dental defects are related to both the use of respective chemotherapeutics, especially vincristine, cyclophosphamide, doxorubicin, and isophosphamide, and to early complications in multidrug chemotherapy - mucositis and vomiting. Vincristine and carboplatin use may promote dentinoma.

Congenital brain tumors in a series of 56 patients.

INTRODUCTION: Central nervous system tumors diagnosed before the end of the first year of life differ from those found in older children and in adults. The differences include mode of clinical presentation, anatomical distribution, histopathological diagnoses, response to therapy, and outcome. MATERIALS AND METHODS: The material consists of 56 children (23 girls and 33 boys), aged at recognition 32 Hbd-12 months. We reviewed charts and MR exams according to age of the onset of symptoms, location of tumors, treatment, histopathology, and outcomes. Data of the outcome were analyzed using Kaplan-Meier plots and chi-square test. RESULTS: Eleven cases were recognized before 6 weeks of life, 24 before the age of 6 months, and 21 were diagnosed up to the end of 1 year of age. Thirty-eight tumors were located in the supratentorial compartment; 18 were infratentorial. Median age of tumors' recognition was 5.2 months; 4.3 months for supratentorial and 7.2 months for infratentorial tumors. We found 18 glial cell tumors (high and low grade), 15 embryonal tumors, and 12 choroid plexus tumors. CONCLUSIONS: The outcome of congenital CNS tumors depends on the size, location, time of diagnosis, histological type of the tumor, and therapeutic option. Neurosurgical procedures are necessary in most cases. Despite the notable advances in therapy, the outcome remains poor.

Congenital intramedullary spinal cord tumours: a report of two cases.

We present two different cases of congenital intramedullary tumours, one of a patient in whom treatment was started without pathological confirmation of a malignant tumour and the other of a primitive neuroectodermal tumour. Magnetic resonance imaging is the most useful tool in the diagnosis of malignant intramedullary tumours and differentiation from other types of spinal cord lesions.

Non-Hodgkin lymphoma (NHL) in children with Nijmegen Breakage syndrome (NBS).

BACKGROUND: Due to small number of patients with Nijmegen Breakage Syndrome (NBS) and Non-Hodgkin lymphoma (NHL) experience in their treatment is limited. PROCEDURE: Since 1996, 17 patients with a median age of 9.5 years who had NBS, were treated for NHL. NHL type, stage, chemotherapy, dose modifications, chemotherapy delays, response to chemotherapy, toxicity, outcome and correlation of drug reduction with response to treatment and outcome were analyzed. RESULTS: Nine patients had TNHL, eight BNHL. TNHL patients received BFM and BNHL LMB type protocols. Doses of cytostatics were reduced in the first chemotherapy courses. Further modifications depended on severity of complications. None of the patients complied with timing of chemotherapy. Complete remissions after induction were achieved in 8 of 9 TNHL and 3 out 8 of BNHL patients. All patients experienced grade 4 toxicities. Two patients died from complications. Six of 17 patients are alive. All received more than 80% of recommended doses of chemotherapy. No differences in the type, number of responses or grade 3 and 4 toxicities between patients receiving less or more than 80% of drug doses were observed. Treatment related deaths concerned patients who received less than 80% of drug doses. CONCLUSIONS: Patients with NBS develop both T and B cell lymphomas. Treatment outcome is poor and might be improved by administering over 80% of drug doses. Although toxicity often depends upon drug doses, our patients experienced equal grade 3 and 4 toxicities whether they received more or less than 80% of the chemotherapeutic agents.

Clinicopathological considerations on angiogenic potential in neuroblastoma Schwannian stroma - poor tumours.

The aim of the study was to determine microscopic angiogenic parameters of neuroblastoma (NB) Schwannian stroma-poor tumours. Furthermore the associations between vascular parameters and clinicopathological features of tumours and basic prognostic factors were analysed. Examined tissue samples from 62 NB came from 39 untreated and 23 chemotherapy pretreated tumours. The clinicopathological data comprised: patients' age, gender, survival, tumour site and stage, tumour histology and MYCN status.The morphological analysis of the angiogenic potential concentrated on examination of vascular patterns - classical type or pathological angiogenesis with mural microvascular proliferation (MVP). The quantitative study included semi-automatic assessment of vascular density (VD) in CD34 stained tumour sections. Pathologic angiogenesis with MVP, including simple and/or glomeruloid type, was encountered in 25 cases and was more frequent in differentiating histology subtype and extraadrenal tumours. VD value ranged from 56 to 385 vessels/mm2 (median 149). Higher VD was connected with younger patient's age. In untreated tumours VD was significantly higher in infants than in children over one year of age. Pathologic type angiogenesis and lower VD were found to be associated with shorter survival. Our study confirmed high vascularization of NB and revealed common occurrence of vascular pattern with MVP. Angiogenic potential in the analysed group showed diversity related to some clinicopathological tumour features. This points toward heterogeneity of NB tumours in vascular aspects, possibly affecting tumours' reactivity to antiangiogenic therapy.

[Conservative treatment in patients with unilateral retinoblastoma]. / Próba leczenia zachowawczego u pacjentów z jednooczna postacia retinoblastoma.

UNLABELLED: THE AIM of our study was to evaluate results of conservative treatment of patients with unilateral retinoblastoma. MATERIAL AND METHODS: Twenty one patients, 11 boys and 10 girls aged 2 months to 4, 5 years (median age 1 year) were studied. Local disease advancement according to Reese-Elsworth was defined in all patients. Neoadjuvant chemotherapy consisting of Vincristine, Etoposide and Carboplatin was administered. After every 2 courses tumour response was evaluated. Sixteen patients were treated with chemotherapy alone. Local treatment including brachytherapy, thermochemotherapy and cryotherapy was implemented and the choice of the method depended on the tumour's localization, size and response to chemotherapy. Statistical analysis using demographic data and survival curves were performed. RESULTS: On completion of treatment all patients achieved tumour regression. Eleven patients are progression free with a follow-up from 10 months to 6 years 4 months (median--2 yrs 5m). In 10 patients relapse was observed. A total of seven enucleations were performed in the examined group. In histopathological examination viable tumour cells were present in all removed eye balls. Distant metastases were not observed in any of these patients. All patients are alive with a follow-up from 10 months to 9 yrs 6 months (median--4 yrs 7 months) from diagnosis. Disease free survival and ocular survival is 44% and 54% respectively. CONCLUSION: Neoadjuvant chemotherapy in unilateral retinoblastoma allows to avoid enucleation in some patients.

[Tumours in newborns and infants up to three months of life. One institution experience]. / Guzy u noworodków i malych niemowlat. Doswiadczenia wlasne.

INTRODUCTION: Newborns and infants up to three months of life are a specific group of population in paediatric oncology due to immaturity of tissues and organs and rarity of neoplastic diseases in this group of patients (pts). There are no strict therapeutic procedures established for these children. THE AIM of our study was to examine distribution of tumours in newborns and infants up to 3 months of age treated in our institution and to present our own experience in the treatment of these patients. MATERIAL AND METHODS: Medical records of 71 pts (37 boys and 34 girls) treated from 1996 to 2004 were reviewed. Distribution of tumour types in newborns and babies from 1 to 3 months of age was analyzed separately. Due to similar growth pattern, response to treatment and it's side effects in newborns and small infants, treatment results were evaluated for the whole group. RESULTS: there were 50 newborns. The most common diagnosis in this group was germ cell tumours (GCT) which constituted 60% of all tumours, amongst them 52% were mature teratomas (MT). The second most common was neuroblastoma (NBL) 22%. There were also 3 cases of soft tissue sarcomas (STS), 2 central nervous system tumours (CNS), 2 retinoblastoma (RB), 2 hepatoblastoma (HB). In the group of 21 babies aged 1-3 months NBL was the commonest (37%) followed by RB, CNS tumours (14% of each) HB and MT (10% of each) and Wilms tumour (WT) and immature teratoma (IT) each 5%. Surgery alone was performed in 48 pts. It concerned pts with MT--28, IT--3 pts, yolk sac tumour (YST)--1 pt and malignant tumours (stage I and II): 8-NBL, 2-CNS tumours, 2 STS, 3-HB, 1-WT. Forty two pts from this group are alive. Six pts died: 2 from surgical complications, 1 from sepsis, 1 of congenital heart defect and 1 from unknown reason at the age of 18 months. It was a patient with severe infantile cerebral palsy. One pt died of disease--relapse of yolk sac tumour, 2 years 4 months after surgery of MT. Eleven pts underwent combined treatment of chemotherapy and surgery: 5 with stage III and IV NBL, 6 with other tumours. One pt with STS at the age of 1 yr 6 months was the tumour bed irradiated after surgery for microscopic tumour residual. Four pts are alive, 4 with NBL and 5 with other tumours. Two pts died from disease: one with NBL and one with IT. Chemotherapy alone was administered to 7 pts in whom local advancement of disease enabled surgery and to pts with RBL. Three out of 7 pts are alive all with RBL. Four pts died: 3 from disease, 1 from infectious complications. Four pts with NBL (2 stage IV and 2 stage IVS) were treated with irradiation to the liver only. Two pts (st. IV) died and 2 (st. IVS) pts are alive. One pt relapsed at age of 2 yrs 3 mths, probably at the primary site which was not visualized at primary diagnosis. One pt, critically ill, died before any treatment. Fifty six out of 70 pts (80%) are alive with a follow up from 1 year to 9 yrs 11 months (median- 4 yrs 4 months). Fourteen pts died (20%), 8 from disease and 6 of other reasons. CONCLUSIONS: 1. GCT and neuroblastoma are the most common tumours in newborns and infants up to 3 months of age. 2. Newborns and small infants with advanced neoplastic disease, similarly to older children can be cured with chemotherapy. 3. Individual approach is warranted in newborns and small infants and treatment should be carried out in specialized centres. 4. All patients who completed treatment of any tumour type should be followed up by a pediatric oncologist.

[Analysis of microvascular density and the expression of vascular-endothelial growth factor (VEGF) and its membrane receptor Flk-1 in neuroblastoma]. / Analiza gestosci naczyniowej oraz ekspresji sródblonowo-naczyniowego czynnika wzrostu (VEFG) i jego receptora blonowego (FLK-1) w neuroblastoma.

AIM: To assess selected angiogenic markers; microvascular density and the expression of VEGF and Flk-1 in relation to clinical features and morphologic types of neuroblastoma. PATIENTS AND METHODS: Eighty-two children with neuroblastoma were studied. Morphological assessment was performed in paraffin embedded tissues of the primary tumours. Microvessels within tumour tissue were counted on immunohistochemically stained sections using anti CD34 antibody. The expression of VEGF and Flk-1 was estimated semiquantitively in immunohistochemically stained sections with adequate antibodies. The results of angiogenic studies were referred to the clinical data: age, clinical stage, localization and site of the primary tumour, serum LDH and ferritin at diagnosis. The correlation between angiogenic markers and morphological type of neuroblastoma was also evaluated. RESULTS: Microvascular density varies in a wide range (32-325/mm(2)). There was no significant statistical difference between previously untreated and tumours assessed after chemotherapy. Analyzing the correlations between the angiogenic markers and clinical features we found a converse relation between the age and microvascular density. The highest expression of VEGF was found in adrenal tumours in comparison to other localizations. Undifferentiated and poorly differentiated tumours presented a higher expression of VEGF and higher vascular density. Non significant higher expression of VEGF and higher vascular density was noticed in smaller <5 cm tumours. CONCLUSIONS: Correlations were found between the microvascular density and the age, diameter and the localisation of the primary tumour. Expression of VEGF depends on the localisation of the tumour. Neuroblastoma tumours arising in small children and poorly differentiated types of neuroblastoma indicate higher angiogenic activity.

[Cancer among adolescents 15-19 years of age. Own experience]. / Nowotwory u mlodziezy w wieku 15-19 lat. Badania wlasne.

BACKGROUND: Adolescents aged 15-19 years are variably included in analyses of childhood cancer. They should be considered separately because tumours that occur in adolescents differ from those in younger children. AIM: To describe the distribution of tumour types and treatment results in this group of patients treated in the Department of Pediatric Oncology at The Children's Memorial Health Institute. METHODS: Retrospective analysis of medical records of patients aged 15-19 years treated in our institution was performed. It included demographic data, tumour types and treatment results. RESULTS: Between 1998-2004, 207 pts, 110 boys and 97 girls aged 15-19 yrs (median--16.5 yrs) were treated. Distribution of tumours was as follows: CNS tumours--74 pts (35.7%), HD -18 pts (8.7%), NHL--13 pts (6.3%), bone tumours--31 pts (15%), STS--23 pts (11.1%), gonadal tumours--12 pts (5.8%), carcinomas--16 pts (7.7%), hepatomas--5 pts (2.4%), neuroblastoma--3pts (1.5%) and other 12 pts (5.8%). Out of 207 pts 130 are alive (62.8%). Seventy seven (37.2%) pts died--64 (83.1%) from disease, 9 (11.6%) from chemotherapy complications, 4 due to other reasons. 111 pts completed treatment and are disease free for 11 months to 7 yrs (median 3 yrs 11 mos) from diagnosis. Nineteen patients are still treated. Treatment results are as follows: CNS tumours--58.1%, HD - 88.8%, NHL--69.2%, bone tumours--51.6%, STS--65.2%, gonadal tumours--83.3%, carcinomas-- 56.25%. CONCLUSIONS: Spectrum of malignancies that occur in adolescents 15-19 years of age differs from younger children. Unlike younger patients epithelial carcinomas of adults are observed in this age group. Outcome of treatment is inferior to younger patients. Adolescents should be offered optimal treatment. This specific group should be studied in many aspects.