Characteristics and treatment results of refractory and relapsed acute myeloid leukaemia in paediatric patients treated in Polish Paediatric Leukaemia/Lymphoma Study Group institutions according to the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 and a review of novel treatment possibilities in paediatric acute myeloid leukaemia.

Introduction: This study aimed to present the clinical features and results of treatment of patients diagnosed with refractory or relapsed acute myeloid leukaemia (AML) in Polish Paediatric Leukaemia/Lymphoma Study Group (PPL/LSG) institutions, treated in accordance with the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012, as their first-line therapy. Material and methods: The outcome data of 10 patients with refractory AML (median age 9.5 years) and 30 with relapsed AML (median age 12 years) were analysed retrospectively. Re-induction was usually based on idarubicin, fludarabine, and cytarabine along with allogeneic haematopoietic stem cell transplant (allo-HSCT) in 5 patients with refractory AML and 7 relapsed AML children. Results: 37.5% (3/8) of refractory AML patients achieved second complete remission second complete remission (CRII). One of ten patients (1/10; 10%) was alive and stayed in complete remission for 34 months after the allo-HSCT. The probability of 3-year event-free survival (pEFS) in this group was 0.125 ±0.11. In the group of relapsed AML patients, the CRII was achieved in 9 patients (34%), and the probability of survival was: pEFS = 0.24 ±0.08; probability overall survival (pOS) = 0.34 ±0.09, with significantly better results achieved in patients who underwent allo-HSCT (pOS = 0.54 ±0.14 vs. 0.08 ±0.08, p < 0.0001). Conclusions: The prognosis of refractory AML and the first AML recurrence in children who were first-line treated in PPL/LSG centres according to Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 is poor. Failures of re-induction treatment particularly result from difficulties in achieving remission. Allogeneic HSCT improves prognosis in children with refractory and first recurrent AML, under the condition it is performed in complete remission. Novel therapeutic approaches are needed to increase the remission rate and improve the outcomes.

Infectious complications in children treated for hodgkin and non-hodgkin lymphomas in polish pediatric leukemia/lymphoma study group: incidence, epidemiology and etiology.

The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial (BI), viral (VI), and invasive fungal disease (IFD) in patients treated for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) between the years 2013-2015. In the analyzed period of time, within the studied group of 328 children diagnosed and treated for lymphomas, at least one infectious complication (IC) was diagnosed i.e. 39.3% children. In these patients there were 350 episodes of IC, therein 80.6% episodes of BI, 11.1% episodes of VI, and 8.3% episodes of IFD. In both groups, NHL and HL patients, a stable level of bacterial infections, with an increase in resistance rates, and increased levels of viral and fungal infections were observed. Profile of BI does not depend on lymphoma type, with predominance of Gram-negative bacteria and higher prevalence of MDR pathogens. The overall survival of lymphoma patients with IC was comparable for different types of infections.

Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in predicting the response to neo-adjuvant chemotherapy in children with advanced malignant peripheral nerve sheath tumor.

PURPOSE: Selected cell-cycle regulators and extracellular matrix proteins were found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology. We aimed to analyze whether initial tumor tissue expressions of survivin, p53, cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST. METHODS: The study included 26 children with MPNST (M/F 14/12, median age 130 months) treated in Polish centers of pediatric oncology between 1992 and 2013. Tissue expression of markers was studied immunohistochemically in the manually performed tissue microarrays and assessed semi-quantitatively as low and high, based on the rate of positive cells and staining intensity. RESULTS: Good response to naCHT was noted in 47.6%, while poor-in 52.4% of patients. The response to naCHT was influenced negatively by the presence of neurofibromatosis NF1 and high initial tumor tissue expression of OPN, survivin, p53 and cyclin D1. Patients with high tumor expression of either OPN, survivin or p53 and those with simultaneous high expression of ≥ 3 of the markers, responded significantly worse to naCHT, than patients, in whom expression of ≤ 2 markers were detected at diagnosis. Nearly, 85% of patients expressing ≥ 3 markers, responded poor to CHT; while 87.5% of children, expressing ≤ 2 markers, were good responders. CONCLUSION: The initial tumor tissue expression of OPN, survivin, p53 and cyclin D1 may serve as markers to predict response to naCHT in pediatric advanced MPNST. Future studies in more numerous group of patients are needed to confirm these preliminary results.

Management and follow-up of Ewing sarcoma patients with isolated lung metastases.

BACKGROUND: Ewing sarcoma (ES) is the second most common pediatric malignant bone tumor with a wide spectrum of clinical presentations. Although metastatic disease to the lungs is often the cause of death, isolated lung metastases at diagnosis are not frequent. The specific role of chemotherapy, surgery, and lung radiation has not been clearly defined. We investigated prognostic factors and the impact of the different treatment modalities in a cohort of patients with ES with isolated lung metastases. MATERIALS AND METHODS: Thirty-eight patients with ES and isolated lung metastases were treated using modern multimodal therapy during the period 2000-2014. According to the imaging characteristics of lung nodules patients were allocated into one of four treatment groups: "0" without nodules, "1" one solitary nodule of <0.5cm or several nodules of <0.3cm, "2" solitary nodule of 0.5-1cm or multiple nodules of 0.3-0.5cm, "3" one pulmonary/pleural nodule of >1cm, or more than one nodule of >0.5cm. Factors predictive of outcome were analyzed. Overall survival was estimated by Kaplan-Meier methods and compared using long-rank test and Cox models. RESULTS: Treatment of the lung metastases was performed in 23 cases (60.5%): twenty patients underwent lung surgery, 6 of them received additional postoperative whole lung radiation; three patients received lung radiation only. Malignant cells were found in all lung nodules of patients from group "3", in 5 (62.5%) patients from group "2", and none of the group "1". There was a correlation between histological response of the primary tumor and outcome. Three-year estimates of EFS and OS were 45.19% and 60.7%, respectively. Patients with good response measured by chest CT had significantly better EFS than patients with poor response (81% vs. 27.66%, respectively, p=0.006). CONCLUSIONS: Metastatectomy may have a role in the treatment of highly selected patients with ES and isolated lung metastases depending on the histologic response to therapy. Further studies are needed to better define the use of surgery and the response-adapted criteria in the upfront management of this population.

Infratentorial ependymomas--a study of the centre in Katowice.

The aim of the study was to assess the correlation of the results of the treatment of infratentorial ependymomas with the degree of resection and histopathological diagnosis. The study was conducted on a group of 19 patients, 13 boys and 6 girls aged 3 months to 16 years, with infratentorial ependymoma treated at the Department of Paediatric Neurosurgery of the Medical University of Silesia in Katowice from January 2000 until December 2008. The most significant factor having an impact on overall survival and progression-free survival was totality of tumour resection. There has been no statistically significant influence of the histopathological type of ependymoma on the result of treatment. The tendency to report better results of treatment of non-anaplastic ependymoma seems to derive from a statistically higher frequency of total removal of tumours of this type.

Validation of a multi-modal treatment protocol for Ewing sarcoma--a report from the polish pediatric oncology group.

BACKGROUND: Ewing sarcoma (ES) is the second most common paediatric malignant bone tumor. Advances in multi-disciplinary care have resulted in significant improvement in cure rates over the last decades. However, the generalization of those results in countries traditionally excluded from large cooperative trials has yet to be demonstrated. We report the results of modern multi-disciplinary care for patients with ES in Poland. PROCEDURES: One hundred and thirty-two patients with ES were treated using modern multi-modal therapy during the period 2000-2009. Overall survival was estimated by Kaplan-Meier methods and compared using long-rank test and Cox models. Factors predictive of outcome in our setting were analyzed to identify distinct risk groups that could help identify areas for improvement. RESULTS: The median age at the time of diagnosis was 12.3 years. With a median follow-up of 5.0 years, the 5-year event-free survival (EFS) and OS estimates for localized disease were 54.88% and 68.29%, respectively. For patients with metastatic disease, 5-year EFS and OS estimates were 36% and 42%, respectively. There was no correlation between age and stage or site. Patients with localized, non-pelvic disease had better outcome than patients with axial tumors (71% vs. 44%, respectively, P = 0.00073). Treatment failure was associated with stage, pelvic primary, poor histological response, and type of local control. CONCLUSIONS: Successful treatment of ES requires optimal systemic and local therapy. We were able to replicate the results of modern multi-modal protocols. Validation of current treatment protocols in countries with more limited cancer treatment resources is required.

Outcome of refractory and relapsed acute myeloid leukemia in children treated during 2005-2011 - experience of the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG).

AIM OF THE STUDY: Recent studies showed relatively better outcome for children with refractory (refAML) and relapsed acute myeloid leukemia (relAML). Treatment of these patients has not been unified within Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) so far. The goal of this study is to analyze the results of this therapy performed between 2005-2011. MATERIAL AND METHODS: The outcome data of 16 patients with refAML and 62 with relAML were analyzed retrospectively. Reinduction was usually based on idarubicine, fludarabine and cytarabine with allogenic hematopoietic stem cell transplant (alloHSCT) in 5 refAML and 30 relAML children. RESULTS: Seventy seven percent relAML patients entered second complete remission (CR2). Five-year OS and disease-free survival (DFS) were estimated at 16% and 30%. The outcome for patients after alloHSCT in CR2 (63%) was better than that of those not transplanted (36%) with 5-year OS of 34% vs. 2-year of 7% and 5-year DFS of 40% vs. 12.5%. Second complete remission achievement and alloHSCT were the most significant predictors of better prognosis (p = 0.000 and p = 0.024). The outcome of refAML children was significantly worse than relAML with first remission (CR1) rate of 33%, OS and DFS of 25% at 3 years and 53% at 2 years, respectively. All survivors of refAML were treated with alloHSCT after CR1. CONCLUSIONS: The uniform reinduction regimen of the documented efficacy and subsequent alloHSCT in remission is needed to improve the outcome for ref/relAML children treated within PPLLSG. The focus should be on the future risk-directed both front and second line AML therapy.

Leptin concentration and nutritional status in the course of treatment in children with brain tumours--preliminary report.

PURPOSE: To assess the nutritional status in children with central nervous system (CNS) tumours, including concentration of leptin, the neuropeptide responsible for regulation of energetic homeostasis in an organism. METHOD: The studied group comprised 44 children with brain tumours, aged (4.02-18.7). In all children during the whole therapy (from the start to the period of 1 year and more after the end of therapy), a number of standard deviations (SDs) for the body mass index (SDS BMI) was derived from anthropometric measurements. Concentrations of leptin were assayed simultaneously. RESULT: The lowest values of the anthropometric indices were found in children during the maintenance therapy. Concentrations of leptin in patients with malignant CNS tumours and significant undernutrition were slightly greater as compared to patients presenting normal nutritional status; however, without statistical significance. CONCLUSION: In children with tumours of the central nervous system, there are quantitative disorders of the nutritional status which correlate with the period of the treatment. The most significant disorders in the nutritional status are observed during maintenance chemotherapy. There was no statistically significant correlation between the concentration of leptin and nutritional status in children with malignant brain tumours during the course of treatment and after its completion.

Clinical factors in relapses of Wilms' tumor--results for the Polish Pediatric Solid Tumors Study Group.

BACKGROUND: The risk factors responsible for recurrences of Wilms' tumor (nephroblastoma) are still under discussion. The aim of the study was to analyze the relationship between relapses of Wilms' tumor and the patients' clinical history. MATERIAL AND METHODS: Clinical data from children registered in the Polish Pediatric Solid Tumors Study Group were analyzed. The clinical stages (CS), pathology variants (high risk: HR, intermediate risk: INT, and low risk: LOW) and chemotherapy regimens were correlated with the outcomes. RESULTS: Recurrences developed in 34 out of 288 (11.8%) patients with Wilms' tumor treated in accordance with International Society for Pediatric Oncology 2001 (SIOP 2001) protocols. Of these 34 patients, 11 initially had CS I, seven were at CS II, four were at CS III, 11 were at CS IV and one had CS V. There were eight patients with second recurrences; of these, seven were in the INT risk group and one in the high histological risk group. There was no correlation between age (p=0.256) or gender (p=0.538) and the risk of tumor recurrence. In the study group, seven out of 10 patients with local recurrences are alive; as are 13 out of 22 patients with distant recurrences (p=0.703). Those who died due to disease progression comprised six out of 26 patients with a first recurrence (four HR, two INT), and seven out of eight with a second recurrence (one HR, six INT). CONCLUSIONS: The prognosis after relapse in initially metastatic patients did not differ from that in patients who had primarily localized disease. The pathology variants probably had more significance.

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.

Individualized tumor response testing profile has a prognostic value in childhood acute leukemias: multicenter non-interventional long-term follow-up study.

A total number of 817 children with acute lymphoblastic leukemia (ALL) and 181 with acute myeloblastic leukemia (AML) were assessed for individualized tumor response testing (ITRT) profile as a prognostic factor in long-term follow-up. For each patient, ITRT, initial response to therapy and long-term outcome were assessed. In initial ALL, an impact on long-term response was shown in ITRT for 13 drugs, while in initial AML only for cytarabine. For patients with ALL, a combined five-drug ITRT profile for prednisolone, l-asparaginase, vincristine, cytarabine and daunorubicin or doxorubicin had predictive value for probability of disease-free survival (pDFS) in univariate analysis, whereas in multivariate analysis, bone marrow response by day 33 was the only prognostic factor. For patients with AML, no factor had prognostic value for pDFS in univariate analysis, while ITRT to cytarabine almost reached significance. In conclusion, ITRT can possibly be regarded as a risk factor in childhood acute leukemias.

Rhabdomyolysis: rare complications with a difficult prognosis in the course of anticancer treatment.

Rhabdomyolysis refers to a number of clinical and biochemical symptoms, which result from the destruction of skeletal muscles. The following triad of symptoms is considered typical: myalgia, muscle weakness, and dark urine. The most common reasons for rhabdomyolysis in children are infections. It has also been reported that rhabdomyolysis may be caused by chemotherapy drugs. The most difficult complication of rhabdomyolysis is renal failure. The authors present a 17-year-old boy diagnosed with Ewing sarcoma and a 16-year-old boy suffering from acute leukemia, both with rhabdomyolysis developed in the course of infection caused by Clostridium difficile, and drug-induced neutropenia.

[Characteristics of extracranial malignant germ cell tumours in two age groups of children (0-10 and 10-18 years). Multicentre experiences]. / Charakterystyka pozaczaszkowych zltosliwych guzów germinalnych u dzieci w dwóch grupach wiekowych 0-10 lat i 11-18 lat. Badania wieloosrodkowe.

UNLABELLED: In order to assess if any differences exist in children germ cell tumours depending on age, we compared some features of germ cell tumours in two age groups:younger than 10 and between 11 and 18 years. MATERIAL AND METHODS: Data of 146 patients with germ cell tumours treated in 15 Polish paediatric oncology departments between 1995 and 2005 were evaluated. They were divided into two groups: 76 children 0-10 years old (group I) and 70 patients 11-18 years old (group II). Tumour morphology, sex of patients, primary tumour and metastases localization, disease stage, biochemical markers, treatment response, disease relapse and long survival were analyzed. Every patient was treated according to the TGM 95 protocol. RESULTS: In group 1, 67 tumours were assessed histologically. 64%t tumours had homogenous structure with yolk sac tumour in predominance and 36% were mixed. Yolk sac tumour (YST) or teratoma as components of mixed tumours were the most commonly found. In older group 64 tumours were examined, 41% were homogenous, and seminoma/dysgerminoma predominated. In 59% mixed tumours the most common components were YST embryonal carcinoma and teratoma. The most common primary site in group I was the sacrococcygeal region while in group II - the gonads. Disseminated disease was recognized mostly in older children. Among two evaluated serum markers, AFP was increased mostly in younger patients (76% vs 44%), and 3HCG in older group (40% vs 9%). Treatment response was comparable in both groups. Two relapses were observed in each group. Poor outcome was noted in 17/140 analyzed patients: 9 (12%) in group I and 8 (11%) in group II. In 12 of patients with poor outcome the cause of death was progression and in 5 of them - treatment complications. CONCLUSIONS: 1. Germ cell tumours in younger and older children differ in histology, primary localization and serum level of biochemical markers. 2. In older patients germ cell tumours are recognized more frequently in advanced clinical stages. 3. Treatment response was comparable in both groups. 4. There is a need to analyze the intensity of chemotherapy to precise the adequate risk groups according to primary treatment response.

Polymorphism of the thymidylate synthase gene and risk of relapse in childhood ALL.

Polymorphisms of genes encoding proteins involved in drug metabolism can influence the efficacy of leukemia treatment. In this population-wide study we aimed to evaluate selected, metabolically active genetic polymorphisms as prognostic markers of treatment efficacy in acute lymphoblastic leukemia (ALL). A total of 51 cases of leukemia relapse were diagnosed in a group of 354 patients with ALL. A strong association between promoter tandem repeat polymorphism of the thymidylate synthase gene and the relapse frequency was found. We believe that genotyping for this variant should be performed in patients treated for ALL to enable further optimizing of treatment protocols.

Differential ex vivo activity of bortezomib in newly diagnosed paediatric acute lymphoblastic and myeloblastic leukaemia.

The proteasome inhibitor, bortezomib, is known to be effective in the therapy of various neoplasms. The objective of this study was the analysis of the ex vivo activity of bortezomib in paediatric acute lymphoblastic leukaemia (ALL), in comparison to paediatric acute myeloid leukaemia (AML). A total of 159 patients entered the study, including 106 ALL (including 86 precursor-B-cell ALL, and 20 T-cell ALL) and 53 AML children. The ex vivo sensitivity to bortezomib and 16 other drugs was studied by MTT assay. Paediatric AML samples were more resistant than paediatric ALL samples to most of the tested drugs, except for cytarabine and thioguanine. With respect to immunophenotype, ex vivo drug resistance in T-cell ALL (T-ALL) was higher for most of the drugs. No differences in drug resistance between T-ALL and common/pre-B-cell-ALL were found for daunorubicin, mitoxantrone and 6-thioguanine. Bortezomib was the only compound which was more active in T-ALL than in common/pre-B-ALL paediatric samples. In conclusion, bortezomib had good ex vivo activity in paediatric T-ALL samples.

Proangiogenic cytokines vascular-endothelial growth factor and basic fibroblst growth factor in childhood lymphadenopathy.

Increased angiogenesis is observed both in the inflammatory and in the neoplasmatic tissue. The aim of the study was to assess the diagnostic significance of serum concentration of vascular-endothelial growth factor (sVEGF) and basic fibroblast growth factor (sbFGF) in the various forms of lymphadenopathy in children. Ninety-four children with lymphadenopathy were studied: group A, 52 patients with lymphadenitis; group B, 42 patients with lymphomas. Group B was divided into subgroups: B(P), children with lymphomas in peripheral lymph nodes and B(M), children with lymphomas in peripheral lymph nodes and mediastinal tumor. The healthy control group was 20 children. Using enzyme-linked immunosorbent assays the authors quantified VEGF and bFGF in serum of healthy children and of children with lymphadenopathy. The sVEGF in group A was significantly higher than controls (313.8 versus 44.6 pg/mL; P <.05) and in group B was 633.4 pg/mL and was significantly higher than controls (P <.0001). The sVEGF and bFGF in group A versus subgroup B(P) were significantly lower (P(VEGF) <.05, P(bFGF) <.05), and sVEGF in subgroup B(P) versus B(M) was significantly lower (P <.05). These results show that the evaluation of serum VEGF concentration might be useful as noninvasive diagnosis of some chronic peripheral lymphadenopathies in children.

[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 failure in children with acute myelocytic leukemia: over 25-year experience of Polish Pediatric Leukemia/Lymphoma Study Group with four consecutive unified treatment protocols for childhood acute myelocytic leukemia]. / Niepowodzenia leczenia w ostrej bialaczce szpikowej u dzieci: ponad 25-letnie doswiadczenia Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków.

Four consecutive intensive unified regimens (BFM-AML-83, PGP-AML 94, PGP-AML 98 AML-BFM 2004 Interim) for acute myelocytic leukemia (AML) have been conducted by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) since 1983. The last one, introduced four years ago is still active, and only preliminary result may be presented. There were 726 children with AML diagnosed (226, 102, 247 and 151 in the I, II , III and IV periods, respectively), and 603 of them were eligible for evaluation (208, 83, 195 and 117, respectively). Complete remission rates were: 71.4%, 67.5%, 81.4% and 87% in consecutive periods, respectively. Five-year overall survival (OS) and event-free survival (EFS) rates were: 33% and 32% for PGP-AML 83 regimen, 38% and 36% for PGP-AML 94 regimen, and 53% and 46% for PGP-AML 98 regimen, respectively. For AML-BFM Interim 2004 the 3-year OS and EFS were 57% and 57%, respectively. Despite continuous improvement of the treatment results, the number of failures have remained too high, but the pattern have changed in the following way: Early deaths (from diagnosis to 15 day of treatment) decreased only in the fourth period to 3%. "Aplasia deaths" (between day 15 and 42) decreased gradually from 16% in the first period to 1.5% and 2.2% in the third and in the fourth period, respectively. Deaths in remission decreased from 10% in first and second period to 3.5% at present. Number of non responders increased between first and second period from 6% to 18%, later decreased to 8.2% at present. These trends e.g. decrease of early death and treatment related mortality reflect both the better efficacy of antileukemic treatment and the improvement of supportive care.