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.

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.

[Prolonged leucopenia in asymptomatic children]. / Przedluzajaca sie leukopenia u dzieci bez objawów chorobowych.

INTRODUCTION: The term leucopenia is still a challenge for clinicists in cases of unknown reasons. There are two main groups of leucopenia: 1. Severe, chronic leucopenia (cyclic, inborn, and idiopathic); 2. Acquired or secondary (reasons: some drugs, infections, viral mainly, autoimmune diseases, haematological abnormalities, neoplasms, hiperspleenism and metabolic diseases). The aim of this investigation was an analysis of asymptomatic, lasting over three months leucopenia myelograms of childhood. MATERIAL AND METHODS: 21 children (6 girls and 15 boys, aged 10-17 years, mean 13.6, median 12 years) were analysed. The children were referred to our clinic by family physicians to investigate the reason of asymptomatic, lasting over three months leucopenia. These children are still under our observation from one till four years. Despite the fact of lasting over three months leucopenia, the general condition of the patients is good. In all the patients the myelogram analysis was performed after May-Grumwald-Giemsa dying, three slides of one hundred cells were counted. Statistical analysis was made using STATISTICA (Stat Soft Polska) programme. RESULTS: Mean number of leucocytes was 3.06x109/ l (median 2.75x109/l, values from 2.46x109/l to 3.53x109/l), mean number of neutrocytes was 1.15x109/l (median 1.07 x 109/l, values from 0.62x109/l to 1470x109/l). Hemoglobin concentration and platelets number were normal. Mean number of marrow cells were within references. However mean number of myelocytes, metamyelocytes, bands and eosynophils were lower than mean number of general population marrow cells (p<0.05). Mean values of myeloblasts, neutrophils, and monocytes were statistically higher than in general population (p<0.05). CONCLUSIONS: 1. Hypothesis of obtained differencess in numer of marrow cells would need to be investigated in broad population of patients. 2. Considering that three children presented with positive familial leucopenia history (in one of them grandmother, in two anothers fathers) genetic predisposition can be expected.

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.

Anemia secondary to valproic acid therapy in a 13-year-old boy: a case report.

INTRODUCTION: Valproic acid is a commonly used anti-epileptic drug. Hematological toxicities are among the occasionally observed adverse effects of this medication. CASE PRESENTATION: We present the case of a 13-year-old Caucasian boy who demonstrated mild anemia 12 months after the introduction of valproic acid therapy. A bone marrow biopsy revealed maturation arrest of proerythroblasts. CONCLUSION: Prompt diagnosis and valproic acid discontinuation resulted in the patient's recovery.

Topotecan exposure estimation in pediatric acute myeloid leukemia supported by LC-MS-based drug monitoring and pharmacokinetic analysis.

Individualization of the topotecan dosing can reduce inter-patient variability, toxicity, and at the same time increases chemotherapy efficacy. Topotecan dosing based on simultaneous drug monitoring and pharmacokinetic analysis can yield more accurate and precise estimation of the topotecan systemic exposure than that attainable with the fixed dosing approach. Therefore, a combined approach could provide a tool assisting the clinicians in individualization of the topotecan dosing. The aim of the study was to estimate the topotecan exposure in pediatric patients with acute myeloid leukemia (AML) based on the plasma concentration-time data and using the pharmacokinetic analysis. The primary goal was achieve the correct estimation of the target plasma area against the topotecan concentration-time curve (AUC) in a 5 day course of cladribine followed by monitored topotecan in pediatric patients with recurrent/refractory AML. A sensitive and selective reversed-phase liquid chromatographic-mass spectrometry (LC-MS) assay was developed to quantify total topotecan in the human plasma samples. This method, with its lower quantification limit of 1 ng/ml, was validated over a linear range of 1-150 ng/ml. Under the proposed approach, the topotecan dosing was selected so as to achieve the final AUC value of 140±20 ng/ml h. The presented analytical and pharmacokinetic data demonstrate that the proposed approach can be a practical, useful, efficient, and accurate tool for individualizing the topotecan dosing in children with AML.

Immunohistochemical expression of procaspase-3 and its clinical significance in childhood non-Hodgkin lymphomas.

Previous studies have shown differences in expression levels of apoptosis regulatory proteins in non-Hodgkin lymphomas (NHLs) and indicated the correlation of procaspase-3 (proC-3) and caspase-3 activation to the response of chemotherapy. We investigated whether proC-3 expression in tumor biopsies of childhood NHLs is related to clinical outcome. Formalin-fixed paraffin-embedded tissues from 58 children with NHL were evaluated for proC-3 expression by immunochemistry analysis. The study included 20 cases of Burkitt lymphoma, 7 cases of diffuse large B-cell lymphoma, 18 cases of anaplastic large cell lymphoma (ALCL), and 13 cases of precursor lymphoblastic lymphoma. The highest expression level of proC-3 was observed in ALCL. In the multivariate analysis the higher clinical stage of disease and higher expression level of proC-3 were independent and appear to be significant prognostic factors of treatment failure. Our results suggest that the high expression level of proC-3 may be a powerful independent predictor of response to chemotherapy and progression-free survival in childhood NHLs.

Childhood rhabdomyosarcoma metastatic to bone marrow presenting with disseminated intravascular coagulation and acute tumour lysis syndrome: review of the literature apropos of two cases.

The paper presents diagnostic and therapeutic difficulties in two adolescents with widespread rhabdomyosarcoma (RMS) presenting with severe haemorrhages resulting from disseminated intravascular coagulation (DIC) and with laboratory features of acute tumour lysis syndrome (ATLS). Other published cases of childhood RMS with DIC at admission have been listed and reviewed. It has been concluded that the clinical picture of a widespread RMS in children may resemble acute hematologic malignancy and pose a big diagnostic problem. That is why the presence of small blue round cells morphologically similar to lymphoblasts and/or myeloblasts in bone marrow (BM), lacking hematopoietic makers, should prompt the pathologist to consider possible diagnosis of RMS. Inclusion of desmin, MyoD1 and myogenin Myf4 to the immunohistochemical panel is obligatory in such cases. When the representative histopathological tumour specimens are difficult to obtain, the flow cytometric immunophenotyping of BM metastases could help the standard morphological/immunohistological diagnostic procedures and advance the diagnosis. Recently, the flow cytometric CD45- CD56+ immunophenotype together with Myf4 transcript has been assigned to RMS cells infiltrating BM. In children with disseminated RMS complicated with DIC rapid polychemotherapy aimed at diminishing the malignancy-triggered procoagulant activity should be initiated. However, in cases with concomitant ATLS the initial doses of chemotherapy should be reduced and the metabolic disorders and renal function monitored. The prognosis in children with RMS metastatic to BM with signs of DIC or ATLS at admission depends on the response to chemotherapy, however generally it is highly disappointing.

[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.

[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.

[Second neoplasms in children with solid tumours in the years 1992-2007. Experiences of Gdansk medical academy]. / Drugie nowoteory u dzieci z guzami litymi w latach 1992-2007. Doswiadczenia osrodka gdanskiego

UNLABELLED: The occurrence of a second tumour is a severe complication of neoplastic disease and its treatment, and it reduces the patient's chances to survive. The aim of the study was to assess the frequency of a second neoplasm and its clinical course in children treated in Gdansk in the years 1992-2007. PATIENTS AND METHODS: There were 420 children and young adults included in the study. They were treated for malignant tumours in this period in the Department of Paediatrics, Haematology, Oncology and Endocrinology Medical Academy of Gdansk. The medical records of these patients were analysed. RESULTS: The second neoplasm was diagnosed in 9 patients, aged 9 to 23 years. They were treated for nephroblastoma - 3 cases, soft tissue sarcoma - 2, Ewing's sarcoma - 1, medulloblastoma - 1, retinoblastoma - 1 and neuroblastoma - 1 case. The second neoplasms were: acute non lymphoblastic leukaemia - 2, soft tissue sarcoma - 2, osteosarcoma - 2, chondrosarcoma - 1, renal cell carcinoma - 1 and glioblastoma multiforme - 1 case. Time between the first and second diagnosis was from 3 and 11/12 to 19 years. Treatment failed in 5 out of 9 children treated for osteosarcoma (2/2), chondrosarcoma (1/1), soft tissue sarcoma (1/2) and acute non lymphoblastic leukaemia (1/2). These patients died of progression of neoplastic disease during 2 to 20 months after the diagnosis of the second tumour. CONCLUSIONS: The diagnosis of the second tumour worsens the prognosis. It is difficult to define the factors that predispose to the second neoplasm. In 5 cases the second neoplasm occurred in the region which was previously irradiated.

Predictive value of multidrug resistance proteins and cellular drug resistance in childhood relapsed acute lymphoblastic leukemia.

PURPOSE: Cellular resistance in childhood acute leukemias might be related to profile and function of multidrug resistance proteins and apoptosis regulating proteins. The aims of the study were: (1) analysis of expression of MRP1, PGP1, LRP, BCL-2 and p53 proteins; (2) correlation with ex vivo drug resistance, and (3) analysis of their prognostic impact on clinical outcome in childhood acute lymphoblastic (ALL) and acute myeloid (AML) leukemia. METHODS: Total number of 787 children diagnosed for initial ALL (n = 527), relapsed ALL (n = 104), initial AML (n = 133) and relapsed AML (n = 23) were included into the study. Mean follow-up period was 3.5 years. Drug resistance for up to 30 anticancer agents was performed by the MTT assay. Expression of all proteins was tested by flow cytometry. RESULTS: Both initial AML and relapsed ALL samples showed higher drug resistance than initial ALL samples. No significant differences were found in drug resistance between initial and relapsed AML samples. The presence of multidrug resistance and apoptosis proteins had no impact on pDFS in iALL and iAML, however strong trend towards adverse prognostic impact of MRP1, PGP and LRP on pDFS in rALL was observed. The same trend was observed for each of analyzed co-expressions of tested multidrug resistance proteins. CONCLUSIONS: The phenomenon of cellular drug resistance in childhood acute leukemias is multifactorial and plays an important role in response to therapy. Expression of MRP1, PGP and LRP proteins, as well as their co-expression play possible role in childhood relapsed ALL.

[Acute renal failure in paediatric oncological disease]. / Ostra niewydolnosc nerek w chorobie nowotworowej u dzieci.

INTRODUCTION: Acute renal failure (ARF) in children with malignancies is a rare clinical situation, but nonetheless it is a serious life threatening condition. It may arise from different clinical situations and may be caused by various factors. The aim of the study was to determine the frequency, aetiology and the course of ARF in children treated for malignancies in the Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical University of Gdansk. MATERIAL AND METHODS: A group of 586 pediatric oncology patients treated between 1992 and 2004 were enrolled in a retrospective study. RESULTS: ARF was diagnosed in 29 cases including: 12 patients with prerenal course of ARF (11 due to septic shock and 1 due to dehydration), 16 patients with intrinsic renal aetiology of ARF (as a complication after cisplatinum and carboplatinum therapy in 2 children, in 2 cases after methotrexate, as a consequence of bilateral nephrectomy due to nephroblastoma in 1 patient and in 11 children with tumour lysis syndrome, including 5 patients with neoplasmatic infiltration of kidneys) and postrenal ARF in 1 patient as a first symptom of a tumour located in the small pelvis (Rhabdomyosarcoma). Renal replacement therapy (dialysis) was necessary in 11 children. Among 29 analysed children, in 20 cases renal failure was reversible. Due to appropriate treatment, ARF in course of tumour lysis syndrome is nowadays reversible. ARF due to septic shock or cytostatics nephrotoxicity is a significant therapeutic problem. In most of the cases it is irreversible. CONCLUSIONS: 1. ARF in these studies occurred in 29 out of 586 children with malignancies (4.9%). 2. Prerenal and renal ARF were the most frequent forms. 3. Implementation of tumour lysis prophylaxis in the treatment of children with blood system proliferative diseases reduces the incidence of ARF. 4. In cases of ARF in children's malignancies close cooperation between paediatric oncologist and nephrologist is necessary.

Carrier frequency of mutation 657del5 in the NBS1 gene in a population of Polish pediatric patients with sporadic lymphoid malignancies.

Nijmegen breakage syndrome (NBS) is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition, in particular to lymphoma and leukemia. Recently, significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation, 657del5, were found in Russian children with sporadic lymphoid malignancies, and in Polish adults with non-Hodgkin lymphoma (NHL). In addition, the substitution 643C>T (R215W) has also been found in excess among children with acute lymphoblastic leukemia (ALL). In an attempt to asses the contribution of both mutations to the development of sporadic lymphoid malignancies, we analyzed DNA samples from a large group of Polish pediatric patients. The NBS1 mutation 657del5 on one allele was found in 3 of 270 patients with ALL and 2 of 212 children and adolescents with NHL; no carrier was found among 63 patients with Hodgkin lymphoma (HL). No carriers of the variant R215W were detected in any studied group. The relative frequency of the 657del5 mutation was calculated from a total of 6,984 controls matched by place of patient residence, of whom 42 were found to be carriers (frequency = 0.006). In the analyzed population with malignancies, an increased odds ratio for the occurrence of mutation 657del5 was found in comparison with the control Polish population (OR range 1.48-1.85, 95% confidence interval 1.18-2.65). This finding indicates that the frequency of the mutation carriers was indeed increased in patients with ALL and NHL (p < 0.05). Nonetheless, NBS1 gene heterozygosity is not a major risk factor for lymphoid malignancies in childhood and adolescence.

[Progress in the treatment of non-Hodgkin's lymphoma (NHL) in children. The report of Polish Pediatric Leukaemia/lymphoma Study Group (PPLLSG)]. / Postep w leczeniu nieziarniczych chloniaków zlosliwych (NHL) u dzieci. Raport Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków u Dzieci (PPGLBC).

Treatment results of non-Hodgkin lymphoma (NHL) in children has been shown in this study. From 1979 to 2003 children were registered with the diagnosis of NHL in oncology centers of Polish Pediatric Leukaemia/Lymphoma Study Group, a group of 397 patients with NHL B, 222 pts with NHL T and 54 pts with anaplastic large cell lymphoma (ALCL). The pts with NHL T have been treated according to BFM-90 protocol. The predominant primary site of disease was mediastinum (59.3%). Complete remission (CR) was achieved by 87%. EFS for all NHL T pts was 65% and 56% for pts with extensive tumours and 73% for pts with tumours < 10 cm. Patients with NHL B were treated according to the adopted LMB-89 protocol. The majority were Burkitts type and presented abdominal location (50%). 80% with disseminated disease. CR was achieved by 89% patients, but 94% with LDH < 500 IU/L and 73% with LDH > 500 IU. The median time of follow up was 53 months. EFS was 73% for all patients. The patients with ALCL were treated according to several protocols. Peripheral nodes were the most often primary location (40%), than mediastinum (24%) and abdomen (21%). EFS for all pts was 63%. Despite great progress in the therapy of NHL in children during 20 years of observation, the results are not satisfactory in disseminated stages. It is necessary to look for new prognostic markers which make it possible to improve classification of patients. Major surgery in advanced stages is not recommended since it delays chemotherapy and fails to improve overall survival. Early detection of neoplasm is one of the most important efforts to improve therapy success.