Pulmonary lesions in early response assessment in pediatric Hodgkin lymphoma: prevalence and possible implications for initial staging.

BACKGROUND: Disseminated pulmonary involvement in pediatric Hodgkin lymphoma (pHL) is indicative of Ann Arbor stage IV disease. During staging, it is necessary to assess for coexistence of non-malignant lung lesions due to infection representing background noise to avoid erroneously upstaging with therapy intensification. OBJECTIVE: This study attempts to describe new lung lesions detected on interim staging computed tomography (CT) scans after two cycles of vincristine, etoposide, prednisolone, doxorubicin in a prospective clinical trial. Based on the hypothesis that these new lung lesions are not part of the underlying malignancy but are epiphenomena, the aim is to analyze their size, number, and pattern to help distinguish true lung metastases from benign lung lesions on initial staging. MATERIALS AND METHODS: A retrospective analysis of the EuroNet-PHL-C1 trial re-evaluated the staging and interim lung CT scans of 1,300 pediatric patients with HL. Newly developed lung lesions during chemotherapy were classified according to the current Fleischner glossary of terms for thoracic imaging. Patients with new lung lesions found at early response assessment (ERA) were additionally assessed and compared to response seen in hilar and mediastinal lymph nodes. RESULTS: Of 1,300 patients at ERA, 119 (9.2%) had new pulmonary lesions not originally detectable at diagnosis. The phenomenon occurred regardless of initial lung involvement or whether a patient relapsed. In the latter group, new lung lesions on ERA regressed by the time of relapse staging. New lung lesions on ERA in patients without relapse were detected in 102 (7.8%) patients. Pulmonary nodules were recorded in 72 (5.5%) patients, the majority (97%) being<10 mm. Consolidations, ground-glass opacities, and parenchymal bands were less common. CONCLUSION: New nodules on interim staging are common, mostly measure less than 10 mm in diameter and usually require no further action because they are most likely non-malignant. Since it must be assumed that benign and malignant lung lesions coexist on initial staging, this benign background noise needs to be distinguished from lung metastases to avoid upstaging to stage IV disease. Raising the cut-off size for lung nodules to ≥ 10 mm might achieve the reduction of overtreatment but needs to be further evaluated with survival data. In contrast to the staging criteria of EuroNet-PHL-C1 and C2, our data suggest that the number of lesions present at initial staging may be less important.

Differentiation between rebound thymic hyperplasia and thymic relapse after chemotherapy in pediatric Hodgkin lymphoma.

BACKGROUND: Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum. METHODS: After completion of CTX, we analyzed computed tomographies (CTs) and magnetic resonance images (MRIs) of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1 trial. In all patients with biopsy-proven LR, an additional fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated. RESULTS: After CTX, a significant volume increase of new or growing masses in the thymic space occurred in 133 of 291 patients. Without biopsy, only 98 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (33/34). All RTH patients (64/64) presented with isolated thymic growth. CONCLUSION: Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass after CTX likely represents RTH.

Segmental chromosomal aberrations as the poor prognostic factor in children over 18 months with stage 3 neuroblastoma without MYCN amplification.

Introduction: Patients with stage 3 neuroblastoma (NBL) according to International Neuroblastoma Staging System (INSS) without MYCN amplification represent a heterogenous group with respect to disease presentation and prognosis. Methods: Retrospective analysis of 40 stage 3 patients with NBL without MYCN amplification was performed. The prognostic value of age at diagnosis (under 18 vs over 18 months), International Neuroblastoma Pathology Classification (INPC) diagnostic category and presence of segmental or numerical chromosomes aberrations were evaluated, as well as biochemical markers. Array comparative genomic hybridization (aCGH) for analyzing copy number variations and Sanger sequencing for ALK point mutations were done. Results: In 12 patients (two patients under 18 months), segmental chromosomal aberrations (SCA) were found and numerical chromosomal aberrations (NCA) were found in 16 patients (14 patients under 18 months). In children over 18 months SCA were more common (p=0.0001). Unfavorable pathology was significantly correlated with SCA genomic profile (p=0.04) and age over 18 months (p=0.008). No therapy failures occurred in children with NCA profile over or under 18 months or in children under 18 months, irrespective of pathology and CGH results. Three treatment failures occurred in the SCA group, in one patient CGH profile was not available. For the whole group at 3, 5 and 10-year OS and DFS were 0.95 (95% CI 0.81-0.99), 0.91 (95% CI 0.77-0.97) and 0.91 (95% CI 0.77-0.97), and 0.95 (95% CI 0.90-0.99), 0.92 (95% CI 0.85-0.98) and 0.86 (95% CI 0.78-0.97), respectively. DFS was significantly lower in the SCA group than in the NCA group (3-years, 5-years, and 10-years DFS 0.92 (95% CI 0.53-0.95), 0.80 (95% CI 0.40-0.95) and 0.60 (95% CI 0.16-0.87) vs 1.0, 1.0 and 1.0, respectively, p=0.005). Conclusions: The risk of treatment failure was higher in patients with SCA profile, but only in patients over 18 months. All relapses occurred in children having obtained the complete remission, with no previous radiotherapy. In patients over 18 months, SCA profile should be taken into consideration for therapy stratification as it increases the risk of relapse and this group may require more intensive treatment.

Go with the Flow-Early Assessment of Measurable Residual Disease in Children with Acute Lymphoblastic Leukemia Treated According to ALL IC-BFM2009.

Measurable residual disease (MRD) is a well-known tool for the evaluation of the early response to treatment in patients with acute lymphoblastic leukemia (ALL). In respect to predicting the relapse the most informative cut-off and time point of MRD measurement during therapy were evaluated in our study. Between 1 January 2013 and 31 December 2019, multiparametric flow cytometry (MFC) MRD was measured in the bone marrow of 140 children with ALL treated according to the ALL IC-BFM2009 protocol. The MRD cut-off of 0.1% and day 33, end of induction, were the most discriminatory for all patients. Patients with negative MRD on day 15 and 33 had a higher 5-year overall survival-OS (100%) and a higher relapse-free survival-RFS rate (97.6%) than those with positive levels of MRD (≥0.01%) at both time points (77.8% and 55.6%, p = 0.002 and 0.001, respectively). Most patients with residual disease below 0.1% on day 15 exhibit hyperdiploidy or ETV6-RUNX1 in ALL cells. Measurement of MRD at early time points can be used with simplified genetic analysis to better identify low and high-risk patients, allowing personalized therapies and further improvement in outcomes in pediatric ALL.

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.

Assessment of Waldeyer's ring in pediatric and adolescent Hodgkin lymphoma patients-Importance of multimodality imaging: Results from the EuroNet-PHL-C1 trial.

BACKGROUND: In the EuroNet Pediatric Hodgkin Lymphoma (EuroNet-PHL) trials, decision on Waldeyer's ring (WR) involvement is usually based on clinical assessment, that is, physical examination and/or nasopharyngoscopy. However, clinical assessment only evaluates mucosal surface and is prone to interobserver variability. Modern cross-sectional imaging technology may provide valuable information beyond mucosal surface, which may lead to a more accurate WR staging. PATIENTS, MATERIALS, AND METHODS: The EuroNet-PHL-C1 trial recruited 2102 patients, of which 1752 underwent central review including reference reading of their cross-sectional imaging data. In 14 of 1752 patients, WR was considered involved according to clinical assessment. In these 14 patients, the WR was re-assessed by applying an imaging-based algorithm considering information from 18 F-fluorodeoxyglucose positron emission tomography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. For verification purposes, the imaging-based algorithm was applied to 100 consecutive patients whose WR was inconspicuous on clinical assessment. RESULTS: The imaging-based algorithm confirmed WR involvement only in four of the 14 patients. Of the remaining 10 patients, four had retropharyngeal lymph node involvement and six an inconspicuous WR. Applying the imaging-based algorithm to 100 consecutive patients with physiological appearance of their WR on clinical assessment, absence of WR involvement could be confirmed in 99. However, suspicion of WR involvement was raised in one patient. CONCLUSIONS: The imaging-based algorithm was feasible and easily applicable at initial staging of young patients with Hodgkin lymphoma. It increased the accuracy of WR staging, which may contribute to a more individualized treatment in the future.

Comparison of Interim PET Response to Second-Line Versus First-Line Treatment in Classic Hodgkin Lymphoma: Contribution to the Development of Response Criteria for Relapsed or Progressive Disease.

In first-line treatment of Hodgkin lymphoma (HL), Deauville scores 1-3 define complete metabolic remission. Interim 18F-FDG PET is also used for relapse-treatment adaptation; however, PET response criteria are not validated for relapse treatment. Methods: We performed a pairwise comparative analysis of early response to first- and second-line treatments in 127 patients with classic HL who experienced relapse. The patients participated in the prospective, multicenter EuroNet-PHL-C1 study. Residual uptake was measured retrospectively using the qPET method, a validated semiautomatic quantitative extension of the Deauville score. Empiric cumulative distribution functions of the qPET values were used to systematically analyze the response to first- and second-line treatments. Results: Individual patients responded variably to first- and second-line treatments. However, the empiric cumulative distribution functions of the qPET values from all patients were nearly superimposable. Conclusion: The findings support that first- and second-line treatments in HL do not require different response criteria.

Polymorphisms of SLC19A1 80 G>A, MTHFR 677 C>T, and Tandem TS Repeats Influence Pharmacokinetics, Acute Liver Toxicity, and Vomiting in Children With Acute Lymphoblastic Leukemia Treated With High Doses of Methotrexate.

Introduction: High dose methotrexate (HD-Mtx) is highly effective and significantly improves overall acute lymphoblastic leukemia (ALL) patients survival. The pharmacodynamics of Mtx depends on the polymorphism of genes encoding proteins engaged in the folate metabolism pathway. The aim of the current study is to determine the relationship between variants of folate metabolism-related genes and the frequency of acute toxicities of HD-Mtx. Material and Methods: A group of 133 patients aged 1.5-18.1 years (median: 6.3) was treated in accordance with the ALL-IC-2002 and ALL-IC-2009 protocols. The following polymorphisms were determined: 80 G>A SLC19A1 (solute carrier family 19 member 1; rs1051266) with direct DNA sequencing, as well as 677 C>T MTHFR (methylenetetrahydrofolate reductase; rs1801133) and the tandem repeats of the TS (thymidylate synthase) with PCR technique. HD-Mtx organ toxicities were evaluated based on the laboratory tests results and the National Cancer Institute criteria. Results: In patients with genotypes AA for SLC19A1 and CC or CT for MTHFR Mtx steady state concentrations (Css) and AUCinf were distinctly higher. In patients with genotype 3R/3R for TS initial elimination rate constant was significantly higher (P = 0.003). Patients receiving Mtx at the dose of 5 g/m2 had lower clearance (4.35 vs. 8.92 L/h/m2) as compared to the ones receiving 2 g/m2 that indicates non-linear Mtx elimination at the higher dose. Liver impairment was the most frequently observed toxicity. The homozygous genotype was associated with a significantly higher incidence of hepatic toxicity for both the SLC19A1 (P = 0.037) and TS (P = 0.002). Logistic regression analysis indicated an increased risk of vomiting for the 2R/3R genotype of the TS gene (OR 3.20, 95% CI 1.33-7.68, P = 0.009) and for vomiting and hepatic toxicity for the 3R/3R genotype (vomiting: OR 3.39, 95% CI 1.12-10.23, P = 0.031; liver toxicity: OR 2.28, 95% CI 1.05-4.95, P = 0.038). None of the acute toxicities differed between the analyzed dosing groups. Conclusions: Determination of polymorphisms of SLC19A1, MTHFR, and TS genes might allow for a better prior selection of patients with higher risk of elevated Mtx levels. Our study is the first one to report the increased risk of hepatotoxicity and vomiting in patients with TS polymorphisms.

Polyneuropathy in Acute Lymphoblastic Leukemia Long-Term Survivors: Clinical and Electrophysiological Characteristics With the Impact of Radiotherapy.

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with one of the highest survival rates. Long-term complications that occur after intensive oncological treatment often impair normal daily functioning. However, existing data on peripheral nervous system condition in ALL survivors remain conflicting. Materials and Methods: The study group consisted of 215 ALL survivors. Patients were treated with New York (NY, n = 45), previous modified Berlin-Frankfurt-Münster (pBFM, n = 64), and BFM95 (n = 106) protocols. Time elapsed between the end of the treatment and the control examination varied from 0.3 to 20.9 years. The analyzed patients underwent a neurophysiological analysis with electroneurography (ENG) of motor (median and peroneal) and sensory (median and sural) nerves as well as electromyography (EMG) of tibialis anterior, vastus lateralis, and interosseous I muscles. To estimate the influence of radiotherapy on recorded neurophysiological responses, a joint analysis of NY, and pBFM groups was performed. Results: Clinical symptoms of polyneuropathy were noted among 102 (47.4%) children during the ALL therapy and in 111 (51.6%) during follow-up. At the time of treatment, polyneuropathy was diagnosed in 57.8% participants from NY group, 35.9%-pBFM and 50.0%-BFM95 (p = 0.145). A significantly higher incidence of polyneuropathy was observed during a follow-up in the NY group (68.9%; p < 0.001 vs. pBFM, p = 0.002 vs. BFM95). The most frequent abnormality within all the protocols was demyelination (NY: 44.4%, pBFM: 59.4%, BFM95: 41.5%), in contrast to the least frequently registered isolated axonal changes. The negative influence of oncological treatment on neurophysiological parameters in ALL survivors was observed. Complex disorders of motor nerves, sensory nerves, and motor unit potentials were registered. Motor-sensory neuropathy was the most frequently found pathology in all analyzed protocols. The harmful effect of radiotherapy was also observed in EMG results. Conclusions: Detailed neurophysiological analysis in long-term childhood ALL survivors has shown generalized abnormalities in registered parameters. To our knowledge, the current study is the largest and one of the most comprehensive ones among those examining disturbances in ENG and EMG in this group of patients. Moreover, we are the first ones to demonstrate the negative influence of radiotherapy on peripheral nerve conduction parameters.

Development of treatment and clinical results in childhood acute myeloid leukemia in Poland.

BACKGROUND: Since 1983 four consecutive unified regimens: acute myeloid leukemia-Polish pediatric leukemia/lymphoma study group (AML-PPLLSG) 83, AML-PPLLSG 94, AML-PPLLSG 98 and AML-BFM 2004 Interim, for AML have been conducted by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). In this paper, we review four successive studies on the basis of acute myeloid leukemia-Berlin-Frankfurt-Munster (AML-BFM) protocol, in which a stepwise improvement of treatment outcome was observed. Treatment results of the last protocol AML-BFM 2004 Interim are presented in detail. METHODS: Three hundred and three patients with de novo AML were treated according to the AML-BFM 2004 Interim at 15 Polish centers from January 1, 2005 to June 30, 2011. A confrontation with previous treatment periods was based upon historical, already published data. RESULTS: In four consecutive periods, 723 children were eligible for evaluation (208, 83, 195, and 237, respectively). Complete remission rates in consecutive periods were: 71, 68, 81 and 87 %, respectively. The 5-year overall survival rates, event-free survival rates, and relapse-free survival rates were 33, 32, and 45%, respectively for AML-PPLLSG 83 regimen; 38, 36, and 53 % respectively for AML-PPLLSG 94 regimen; 53, 46, and 65 % respectively for AML-PPLLSG 98 regimen, and 63, 52, and 64 % for AML-BFM Interim 2004, respectively. Incidence of early deaths and that due to complications (mainly infections) in the first remission decreased over time from 22 to 4.6 % and from 10 to 5.9 %, respectively. CONCLUSIONS: Despite continuous improvement in the treatment outcome, the number of failures still remains too high. Further progress seemed to be possible due to continued cooperation of oncology centers within large international study groups.

[Genotyping and minimal residual disease study in children with acute myeloid leukemia: preliminary results]. / Genotypowanie i oznaczania choroby resztkowej u dzieci z ostra bialaczka mieloblastycznq: wstepne wyniki.

The aim of the paper is to present the initial results of molecular examination which was started in 2006 for children with acute myeloid leukemia. Better knowledge of biology of this disease, can result in establishing of new risk factors what allows more precise patient stratification to different therapeutic groups. Study was obtained patients until to 18 years of age treated according to AML-BFM 2004 INTERIM protocol in 14 centers of the Polish Pediatric Leukemia/Lymphoma Study Group. Mononuclear cells were collected from bone marrow on time points established according to the AML-BFM 2004 INTERIM protocol. Collected cells were isolated on Ficoll gradient, and RNA and DNA were isolated using TRIZOL reagent. To synthesize cDNA an amount of 1 mg of total RNA was used. To perform quantitative RT-PCR and RQ-PCR reactions 4 fusion gene transcripts (AML1-ETO, CBFb-MYH11, PML-RARA /subtype bcrl and bcr3/) were used according to the protocol established by Europe Against Cancer Program. An expression of WT1 gene was tested additionally. An analysis of ABL control gene was used to normalize of achieved results. Determination of duplication of FLT3 gene in DNA sample was performed with starters complementary to JM region. Genotyping was performed in 75 patients with acute myeloid leukemia so far. AML1-ETO fusion gene transcript was found in 14 patients (19%). PML-RARA (subtype bcr3) and CBFB-MYH11 gene transcripts were detected in 3 (4%) and 3 (4%) patients, respectively. Duplication of FLT3 gene was found in 4 (5.3%) cases. Between 67 tested children over expression of WT1 was present in 51 patients (76%). Analysis of MRD level in subsequent time points showed systematic decrease of number of fusion gene transcript copies and gene WT1 expression. To establish the rate of molecular marker presence in AML in children and the influence of the presence of MRD on the treatment results as well, the study has to be conducted on a larger group of patients with longer follow-up.

[Can children with Hodgkin's disease be treated with chemotherapy only?]. / Czy dzieci z choroba Hodgkina moga byc leczone wylacznie chemioterapia?

Currently over 90% of children and adolescents with Hodgkin's disease (HD) can be cured thanks to use of multidrug chemotherapy (CT) combined with involved-field radiotherapy (IF-RT). However, the intensive treatment may increase the risk of late complications which may impair the patients' quality of life. In order to decrease the incidence of late complications the protocol with limited use of IF-RT was introduced in centers of Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). This study presents the treatment results of patients treated with CT only in comparison with the therapy results of children treated with CT and IF-RT. From 1997 to 2006, 634 children (age: 2-22,5 years) with HD were treated in 14 oncological centers of PPLLSG. Majority of patients received CT (3-8 cycles of MVPP/B-DOPA) combined with IF-RT. In 45 patients with IA-IIA stages presenting favorable risk factors (small mediastinal tumor, peripheral nodular mass of a maximum diameter < 6 cm, involvement of less than three nodular regions, ESR < 50 mm after 1 h, histologic type other than lymphocyte depletion and very good treatment response assessed after 3 CT cycles) IF-RT was omitted. Among 634 children first complete remission (RC) was not achieved in 2.4% of patients. Relapses occurred in 24 children (3.9%). The rates of 5-year overall survival (OS), relapse-free survival (RFS) and event-free survival (EFS) were 97%, 96% i 92%, respectively. All patients treated with CT only remain in first CR. All serious late complications (including 7 second neoplasms) occurred in patients treated with CT combined with RT. Seven children died because of severe complications, among them two in first CR (aplastic anemia, sepsis). Our results show that the use of CT only in precisely selected group of patients with HD do not impair the treatment results and may decrease the risk of late life threatening complications. Treatment response assessment with the use of PET may in future increase the number of patients treated without RT and limit the need of the use of invasive diagnostic methods in patients with residual mass.

[Treatment results of children with neuroblastoma: report of Polish Pediatric Solid Tumor Group]. / Wyniki leczenia dzieci ze zwojakiem zarodkowym wspólczulnym: wstepny raport Polskiej Pediatrycznej Grupy Guzów Litych.

Approximately 60 children aged 0-18 years are diagnosed of NBL each year in Poland. About 60% of all patients suffering from NBL have a chance for durable cure. Unfortunately the prognosis for patients within the high-risk group accounting for more than 50% of all NBL patients remains poor despite the introduction of more intensive chemotherapy regimens with radical surgery procedures and megachemotherapy with subsequent stem cell transplantation. Only one third of patients in this group can be cured. To improve the treatment results of the high-risk patient group and to decrease the rate of therapy related side effects current European treatment protocols have been introduced systematically in Poland. In February 2009 information about 389 patients (age 0.1-16.5 years) diagnosed between 2001 and 2008 were obtained. Results of therapy of 319 patients who started treatment from 2001 to 2007 were analyzed. Between 104 infants and 215 children over 1 year of age, stage 4 of disease was found in 25% and 54.5%, respectively. In this period additionally to European treatment protocols, two another protocols were used. Satisfactory treatment results were obtained in 104 infants (5-year event free survival /EFS/=82.6%), irrespective of the type of treatment protocol. Over 5-year EFS for children over 1 year of age in 1, 2 and 3 stage of disease was: 100%, 86.3% and 64.5%, respectively. On the contrary, 107 patients with 4 stage of disease achieved the 5-year EFS of 27% only. Treatment results obtained in patients treated according to the European HR-NBL-1/ESIOP protocol were better than for patients treated according to other treatment protocols (5-year EFS: 31.1% and 16.4%, respectively), but difference between these groups was not significant. Between 2001 and 2007 data reporting increased to 81% from 19% noted earlier. Unfortunately, results of treatment for children over 1 year of age remain still unsatisfactory. That is why there is a need of improvement of modern, unified treatment realization as well as better data reporting. For realization of these aims adequate financial support is essential.

[Complete autologous bone marrow recovery after allogeneic stem cell transplantation in a child with acute monoblastic leukemia]. / Pelna odnowa autologiczna szpiku kostnego po alloprzeszczepieniu u dziewczynki z ostra bialaczka monoblastyczna.

We present a case of autologous bone marrow recovery after allogeneic hematopoietic stem cell transplantation (HSCT) in a 7-year old girl who was treated due to acute myelocytic leukemia. First complete remission is lasting for 81 months after the allo-HSCT. Presented case constitutes an exceptional clinical situation and it indicates that diagnosis of leukemia relapse should be cautiously considered once the autologous bone marrow recovery is observed after allogeneic HSCT.

[Does the residual mediastinal mass have prognostic significance in children with Hodgkin's disease (HD)?]. / Czy obecnosc przetrwalej zmiany w sródpiersiu ma znaczenie prognostyczne w chorobie Hodgkina (HD) u dzieci?

Prognostic significance of residual mediastinal tumor mass in children treated for HD as well as the choice of the optimal management of these cases still remains unknown. In years 1994-2001 in 10 PPLLSG participating centers 480 children (age 2-19.7 years) were treated for HD (stages I-IV). In 338 cases initial mediastinal/lung hilus involvement was present. All patients with initial mediastinal/lung hilus involvement were treated with multidrug chemotherapy combined with involved field radiotherapy. In five cases remission was not achieved. Complete remission (CR) was achieved in 226 patients and uncertain complete remission (UCR) in 107 patients, in whom after completion of planned treatment residual changes in mediastinum/lung hilus were identified in radiological examinations. Twenty four children with persistent mediastinal tumor underwent thoracoscopy or thoracotomy. In only one case histopathological examination revealed the presence of neoplastic cells in mediastinal mass tissue, in 2 another cases cystic changes in mediastinum were present, in one case thymic tissue was identified, necrotic tissue was present in 20 cases. Among 107 children with residual mediastinal tumor and 226 patients with CR achieved, relapses occurred in 6 and 18 patients respectively. Over 5-year relapse-free survival was 92.4% and 91.3% respectively. Patients with the presence of mediastinal/lung hilus tumor after the completion of the treatment do not have an increased risk of relapse, but before the completion of therapy they require careful, clear-sighted and repeated examinations including computed tomography (CT), magnetic resonance imaging (MRI) and especially positron emission tomography (PET) to evaluate the nature of persistent lesions. Only in clinically and radiologically doubtful cases tumor biopsy with subsequent histopatological examination should be performed.

[Program of care for children and adolescents after completion of therapy for cancer]. / Program opieki nad dziecmi i mlodzieza po zakonczeniu leczenia nowotworu.

Based on our center's experience and data from literature we present a system of care for patients cured from cancer in childhood. The scope of proposed care will be to increase the rate of detection of late complications, improve efficacy of medical care, improve quality of research, and introduce changes in treatment regimens in order to decrease the incidence of late complications of treatment while maintaining or even improving cure rates and reduce cost of care.

Lymphocyte populations in lymph nodes in different histological types of Hodgkin's disease in children.

Proliferating Reed-Sternberg and Hodgkin's cells within the lymph node in Hodgkin's disease (HD) affect the surrounding cells, which results in alterations of the proportion between T and B lymphocytes and the activation of these cells. The purpose of this study was to assay the changes within lymphocyte populations in lymph nodes in different types of HD. The lymph nodes of 10 children with nonmalignant, reactive changes, and 31 children with HD of the following types: mixed cellularity (MC; 11 cases), nodular sclerosis (NS; 17 cases) and lymphocyte depletion (LD; 3 cases) were included in the study. The percentage of T lymphocytes (CD3+), B lymphocytes (CD22+), T cell (CD4+ and CD8+) and B cell subsets (kappa+ and lambda+ light chain) were assayed with flow cytometry. The ratio of T:B lymphocytes in reactive lymph nodes and in NS type of HD was similar. An increase of the T cell percentage (resembling an increase of the CD4+ subset) and a decrease of B cells resulted in a high ratio of T:B and was noted in the MC and LD types of HD. These HD types were associated with marked changes in lymphocytes within the lymph node, which suggested a different effect of proliferating Reed-Sternberg and Hodgkin cells in HD on the surrounding cells.

[Can intensive induction chemotherapy eradicate retroperitoneal lymph node metastases in children over 1 year of age with stage 4 neuroblastoma?]. / Czy intensywna chemioterapia indukcyjna moze spowodowac eradykacje zmian w pozaotrzewnowych wezlach chlonnych u dzieci powyzej 1 r.z. z neuroblastoma w 4 stopniu zaawansowania?

The prognosis in patients over 1 year of age with stage 4 neuroblastoma (NBL) is poor in spite of intensive treatment. The choice of intensive chemotherapy and extension of the surgery, especially in the case when the tumor is localized in the abdomen, is still controversial. Between 1991-2001 there were 61 patients with NBL treated in our Department; 28 of them were older than 1 year and had stage 4 with the tumor localized in the abdomen. All children received intensive chemotherapy according to Japanese protocol. Three children with disease progression during intensive treatment where excluded from further analysis. In 22 children with good or very good response to chemotherapy, the surgery was performed. In 4 patients it was local surgery. In 18 patients the tumor was removed with all visible retroperitoneal lymph nodes (so called Tsuchida surgery). The histopathological evaluation was performed in 17 patients with Tsuchida surgery and in 13 cases metastases in retroperitoneal lymph nodes were found. The 5-year overall survival was significantly better in the group with Tsuchida surgery performed (0.66 vs 0.21, p=0.044) for the patients in stage 4. After the intensive induction of chemotherapy the metastases in retroperitoneal lymph nodes can still be found. The removal of the tumor with all retroperitoneal lymph nodes can improve treatment results in patients with advanced abdominal neuroblastoma, but it is necessary to investigate more patients and to prolong the observation period.

[Influence of age on treatment results in children and adolescents with Hodgkin's disease]. / Wplyw wieku na wyniki leczenia dzieci i mlodziezy z choroba Hodgkina.

Over the last few years, treatment failures (progression, relapse) in Hodgkin's disease (HD) occurred mainly in elder children treated in the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) participating centers. That is why analysis of the influence of age on the treatment outcome in children and adolescents treated with the protocol introduced in 1997 was performed. In years 1997-2001, in 10 centers of PPLLSG, 280 patients (age 2.3-18.8 years) were treated for HD. In all patients MVPP and B-DOPA chemotherapy with or without radiotherapy was introduced. Among 280 treated children the first remission was achieved in 275 patients (98.2%). Relapses occurred in 11 patients (4%). The 5-year probability of overall survival, relapse-free survival (RFS) and event-free survival (EFS) was 99%, 93% and 90%, respectively. All children with relapse were over 10 years old at the time of diagnosis (range: 10.6-17.1, median 14.6 years); mediastinal tumor mass was present in all of them. The logistic regression analysis did not reveal the border value for increasing the probability of relapse or event, thus age of 10 years (age of the youngest child with relapse) was identified as the border value. The probability of 5-year EFS and RFS for children over and under the 10th year of age was 98%, 92% and 100%, 92%, respectively. The differences were not statistically significant. Among children over the 10th year of age some features of the disease occurred more frequently: female sex, shorter history of the disease, presence of mediastinal tumor, greater stage of the disease, NS histopathological type of the disease, presence of general signs and ESR over 50 mm, greater tumor burden and higher number of involved lymphatic regions. Among the patients over the 10th year of age, the presence of the general signs and mediastinal tumor influenced the occurrence of relapses substantially. The aim of the further treatment modifications ought to comprise the need of better treatment outcome, especially in patients over the 10th years of age in which unfavorable prognostic factors are identified. child with relapse) was identified as the border value. The probability of 5-year EFS and RFS for children over and under the 10th year of age was 98%, 92% and 100%, 92%, respectively. The differences were not statistically significant. Among children over the 10th year of age some features of the disease occurred more frequently: female sex, shorter history of the disease, presence of mediastinal tumor, greater stage of the disease, NS histopathological type of the disease, presence of general signs and ESR over 50 mm, greater tumor burden and higher number of involved lymphatic regions. Among the patients over the 10th year of age, the presence of the general signs and mediastinal tumor influenced the occurrence of relapses substantially. The aim of the further treatment modifications ought to comprise the need of better treatment outcome, especially in patients over the 10th years of age in which unfavorable prognostic factors are identified.

[Rare tumours--are they really rare in the Polish children population?]. / Nowotwory rzadkie--czy rzeczywiscie rzadkie w populacji polskich dzieci?

Clear statement that pediatric neoplasms are really rare is not easy. Thus the incidence of rare tumours in children has not been defined so far. The paper efforts to assess the topic of rare tumours of childhood in the Polish population. Following two categories are proposed: tumours typical for adults, but possible in children (neoplasms of epithelial origin--mainly carcinomas, melanomas, carcinoids) and paediatric tumours consisting less than 10% of cases in corresponding clinical groups according to the ICCC classification. Data on 317 patients aged 0-18 years treated in centres associated in the Polish Paediatric Group for Solid Tumours (PPGST) were analysed. Classical adult malignancies were registered in 130 patients: carcinomas in 90 (mean age 12.6 +/- 4.5 years), melanomas in 25 (mean age 9.4 +/- 4.9) and carcinoids in 9 (mean age 14.5 +/- 1.2 years). Non epithelial neoplasms were registered in 187 patients (mean age 10.4 +/- 5.5). That group included rare tumours of soft tissue, CNS, bones and other organs. Treatments of certain groups were specified by separate therapeutic protocols within PPGST. Rare malignancies of adult-type among children under 18 years of age in Poland comprised 1.5% of all pediatric neoplasms. The incidence of adult-type neoplasms increased with age until 14 years. In patients over 15 years of age the number of registered cases decreased. It may suggest a first peak of incidence in early adolescence or an underestimation of number of patients with carcinoma aged over 15 years. In the analyzed group, the mean age of patients with carcinomas and other epithelial and unspecified tumours significantly exceeded the age of children with rare neoplasms of non-epithelial origin (12.1 +/- 4.7 vs 10.4 +/- 5.5 years; p<0.05). A very young age at diagnosis of malignant melanomas (mean 9.4 years) and numerous cases of carcinomas affecting the digestive tract (n=24; 27% of all carcinomas), especially those located in colorectal region (n=10), seem surprising. The preliminary analysis of the collected data on rare neoplasms in Poland encourage to undertake a prospective study, meant to link the epidemiology and characteristics of rare epithelial tumours in childhood with diagnostic and therapeutic suggestions for these types that are not coordinated within Polish Paediatric Group of Solid Tumours.