[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.

[Long-term observations of children with acute lymphoblastic leukemia and high leukocytosis treated according to modified "New York" protocols (1987-2003)]. / Wieloletnie obserwacje dziec z ostra bialaczka limfoblastyczna i wysoka liczba krwinek bialych leczonych wedlug zmodyfikowanych protokolow "Nowy Jork" (1987-2003).

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Due to new therapeutic schedules and cooperation between oncological centers it is curable in more than 80% of affected children. For the optimalization of the therapy there is necessary to assess the risk criteria that have influence on the treatment results in the certain groups of patients. Hyperleukocytosis and the age (less than 1 year and more than 10 years) are known as unfavorable risk factors. The study was designed to assess the long-term treatment results in children with ALL and the initial leukocytosis over 50 000/mm3 with the use of the modified "New York" protocols. We present the treatment results of 340 children with ALL treated in nine centers of Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) according to three consecutive versions of modified "New York" protocol (group I, II, and III) between 1987 and 2003. Within the analyzed groups the first complete remission (I CR) was achieved in 91%, 95% and 96% of the patients, respectively. Relapses occurred in 37%, 21.5% and 26% of the patients and 3.7%, 1.8% and 5.7% of children died in the I CR due to complications, in the I, II and III therapeutic group, respectively. Obtained 5-and 10-year event-free survival (EFS) were 56% and 53.5% for the group I and 73% and 73% for the group II. Five-year EFS for the group III was 67%. The implementation of the New York protocol in 1987 and New York I in 1997 has improved the treatment results in children with ALL and initial leukocytosis over 50 000/mm3. Protocol New York II did not further improve the treatment results. Among analyzed parameters (age, gender, the initial leukocytosis, the blast cells immunophenotype) only age had the statistical significance. The implementation of modified "New York" protocols has improved the treatment results in children with ALL and initial leukocytosis over 50 000/mm3 compared to previous results.

[Analysis of risk factor treatment failures in therapeutic programme for malignant germ cell tumours in children. Multicentre prospective study of Polish Pediatric Group for Solid Tumours 1998--2006]. / Analiza czynników ryzyka niepowodzenia terapii w programie leczenia dzieci ze zlosliwymi guzami terminalnymi. Wieloosrodkowe badania prospektywne Polskiej Pediatrycznej Grupy Guzów Litych (PPGGL) w Latach 1998--2006.

AIMS: The aim of the study was the analysis of risk factors of therapeutic failures in children with malignant germ cell tumours treated within the multicentre programme of PPGGL from 1999--2006. MATERIALS AND METHODS: The investigated group included 18 (14.3%) patients, of 123 who have finished the treatment of malignant germ cell tumour, in whom no remission was obtained or relapse occurred. All the patients were treated according to the TGM 95 programme. Both clinical and morphological data of the group have been analysed. RESULTS: Among 18 patients with therapeutic failures 12 died. Two patients from the high risk group died of complications of the treatment--sepsis during neutropenia after chemotherapy and one after haemorrhage to the central nervous system. The other 9 died from progression of malignancy, 6 of them belonged to the high risk group. 10 (82%) of 12 patients who died had extragonadal location and in 11 (92%) the tumour was in stage III or IV of the disease. The most frequent histology in this group was mixed germ cell tumour with component of yolk sac tumour or carcinoma embrionale. 92% patients had elevated AFP, in 4 it was above 15000 ng/ml. In 11 (92%) patients primary chemoresistance was observed, and radical surgery was not possible for the reason of advanced stage of the disease. In 6 patients relapse occurred. In 3 patients testis was the primary location (I and II stage), in 3 patients the tumour was localized in the sacrococcygeal region (III and IV stage). All the patients are alive in remission after second line therapy, with 78 months (median) of follow-up. CONCLUSIONS: 1. The main risk factor for therapeutic failures in malignant germ cell tumours was primary chemoresistance in inoperable tumours of the sacrococcygeal region. 2. The mortality of treatment complications was low. 3. The relapse of cancer was not a risk factor for therapeutic failure due to the high probability of second remission 4. Therapeutic failures are mainly observed in patients with mixed germ cell tumour with components of yolk sac tumour or carcinoma embrionale. 5. Tumour chemoresistance should be considered an essential factor in identifying high risk patients.

[Acute lymphoblastic leukemia in children with initial leucocytosis above 50,000/mm3: summary of treatment results of Polish Pediatric Leukemia/Lymphoma Study Group]. / Ostra bialaczka limfoblastyczna u dzieci ze wstepna leukocytoza powyzej 50,000/mm3: podsumowanie wyników leczenia Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków.

Initial leucocytosis, presence of t(9;22) and t(4;11) translocations and poor response to therapy with steroids or induction chemotherapy are still included to poor risk factors group. From 1981 to 1986, children with acute lymphoblastic leukemia (ALL) and initial WBC above 50,000/mm3, achieved significantly worse treatment results than children with lower WBC: over 6-year disease-free survival were respectively 33% and 60%. In attempt to improve treatment results in children with hyperleucocytosis, modified American protocols called: New York (1987), New York I (1997), and New York II (1999) were introduced consecutively in the centers of Polish Pediatric Leukemia/ Lymphoma Study Group. Actually treatment results obtained with those protocols in three groups of patients: group I: 214 children (1987-1996), group II: 58 children (1997-1999), and group III: 77 children (1999-2001) are presented. The observation was completed in March 31, 2004. In evaluated groups the first complete remissions (CR) were achieved in 91%, 95%, and 96% of patients, respectively. Relapses occurred in 72 patients of group I (37%), in 12 patients of group II (21%), and in 13 patients of group III (18%). The 5-year overall survivals were: 62%, 79%, and 78% (p=0.05) respectively; 5 year event-free survivals (EFS) were: 52%, 74%, and 69% (p=0.01) respectively. A significant improvement in treatment results in second compared with first group was achieved. Treatment results obtained with New York II are comparable with results obtained with New York I. The analysis of treatment results achieved shows the improvement of the prognosis in children with ALL and initial WBC above 50 000/mm3 in comparison with patients treated before 1987. There is strong necessity of unification of risk group qualification criteria in childhood ALL in term of comparable estimation treatment results achieved in different centers all over the world.

[Ovarian malignant tumours. Efficacy of germ cell and sex cord tumour treatment protocol in Poland]. / Nowotwory zlosliwe zlokalizowane w obrebie jajników. Ocena skutecznosci programu leczenia zlosliwych guzów germinalnych i guzów sznurów plciowych u dzieci w Polsce.

UNLABELLED: Approximately 1% of all malignant tumours among children are localized in the ovary. The majority belongs to germ cell tumours and occurs in the peripubertal period. AIM of the study was the evaluation of the efficacy of malignant ovarian germ cell tumour treatment programme in children. MATERIAL AND METHODS: Since 1998, 40 girls with malignant ovarian tumours were enrolled in the multicentre trial. Mixed germ cell tumours with yolk sac elements and dysgerminoma occurred the most often. Alfa-fetoprotein (AFP) was increased in almost one half of patients. Tumour exceeded the ovary margin in more than half the patients and 25% were qualified as high risk group. 38 children completed the treatment. All but one patient with neuroblastoma received TGM protocol (Tumeurs Germinates Malignes). A VBP regimen (vinblastine, bleomycin, cisplatin) was applied in 19 girls, VIP regimen (etoposide, ifosfamide, cisplatin) in 16, two received no chemotherapy. Due to delayed remission after first-line chemotherapy it was prolonged with ABK (adriamycine, bleomycine, carboplatin) in 3 patients, 1 megachemotherapy regimen with autologous bone marrow transplantation was realized, one patient received a 1.5 year long oral chemotherapy. All the children underwent surgery, 34 primary (56% complete), 12 secondary (75% complete). 8 children were operated twice. RESULTS: Among 34 children with germ cell tumours and 3 with sex cord tumours who completed the treatment all are alive in the first remission. 1 child with neuroblastoma localised in the ovary died due to recurrence. A median follow-up period was 42 months. CONCLUSIONS: The TGM protocol appears to be highly efficient in treatment of germ cell tumours even in advanced stages.

[Testicular malignant tumours. Efficacy of germ cell and sex cord tumours treatment protocol in Poland]. / Zlosliwe nowotwory jader. Ocena skutecznosci programu leczenia zlosliwych guzów germinalnych i guzów sznurów plciowych u dzieci w Polsce.

UNLABELLED: Approximately 2% of of all malignant tumours in boys are localised in the testis. Among them 80% are germ cell tumours with the malignant elements of yolk sac tumour. AIM of the study was evaluation of the efficacy of malignant testicular tumour treatment programme in children. MATERIAL AND METHODS: Since 1998 31 boys aged 1 month to 18 years (median 14 years) with malignant testicular tumours were enrolled in the multicentre trial. Patomorphologically clear yolk sac tumour (33%) and mixed germ cell tumour (42%) with the majority of yolk sac tumour component or carcinoma embryonale, occurred most often. Alfa-feto-protein was increased in 63% and choriogonadotropin in 26 patients. 61% patients had local clinical stage and the tumour was localized in the testis. In 39% patients tumour exceeded the testis margin. 4 patients were excluded from analysis as 3 are actually treated and 1 died on the second day of admittance to hospital. All patients received TGM 95 regimen (Tumeurs Germinales Malignes). Surgery (orchidectomy) was applied in 27 boys, 26 were primary (81% complete), 3 secondary (100% complete). 33% received no chemotherapy after surgery, in 41% VBP protocol (vinblastine, bleomycin, cisplatin) was given and in 26%o VIP protocol (ethoposide, ifosphamide, cisplatin). Two patients received also ABK (adriamycine, bleomycin, carboplatin). RESULTS: Among 26 children with germ cell tumours, 25 (96%) are alive, 23 (88%) are in first remission after completion of treatment. One child died due to central nervous system metastases. 2 children had local recurrence treated with chemotherapy or surgery with good result. Median follow-up is 45 months. CONCLUSIONS: TGM regimen is highly efficient in the treatment of malignant testicular tumours. Problems occur in cases of disseminated disease.

[Megachemotherapy followed by autologous haematopoietic stem cell rescue in children with high risk CNS tumours]. / Megachemioterapia z przeszczepieniem autologicznych hematopoetycznych komórek macierzystych u dzieci z nowotworami oun wysokiego ryzyka.

AIM: the Lublin bone marrow transplantation unit experience in megachemotherapy followed by autologus haematopoietic stem cell transplantation in children with high-risk CNS tumours is described. MATERIAL AND METHODS: 9 patients (8 boys and 1 girl) treated in our department between 1999-2004, with high risk malignant brain tumours were included into the study. Median age of the patients was 10 years (range 4-18 years). The group consisted of 5 cases of medulloblastoma, and single cases of ependynmoma, teratoma, astrocytoma anaplasticum and glioblastoma. Stem cell apheresis from peripheral blood was performed during chemotherapy after surgery. Megachemotherapy consisted of carboplatin in total dose 1200 mg/m2, etoposide in total dose 800mg/m2 and melphalan in total dose 200 mg/m2 in five patients. Remaining four children received carboplatin in total dose 1800 mg/m2, etoposide in total dose 750 mg/m and tiothepa in total dose 900 mg/m2. RESULTS: two patients relapsed one and two months after megachemotherapy respectively. No transplant related mortality was observed. Seven children are alive and well with the median observation time 23 months. CONCLUSION: megachemotherapy followed by stem cell rescue is a safe and feasible procedure in children with malignant brain tumours and may improve results of the treatment in high-risk patients, but these results should be con firmed in larger series of patients.

[Malignant germ cell tumours. Multicenter prospective trial in Polish Pediatric Group for Solid Tumours (years 1998-2000)]. / Zlosliwe guzy germinalne u dzieci. Wieloosrodkowe badania prospektywne Polskiej Pediatrycznej Grupy Guzów Litych w latach 1998-2002.

UNLABELLED: Germ cell tumors constitute about 3% of all pediatric malignancies. Since 1998 the multicenter trial was initiated in Poland. MATERIAL AND METHODS: 95 children (aged from 1 month to 17 years--mean 9.2 years) were registered. There were 38 boys and 57 girls. Diagnosis was made on histopathological examination in 88% patients (pts) and in 12% was established on imaging and biochemical findings (elevated AFP). Mixed germ cell tumor and yolk sac tumor prevelaged. AFP was elevated in 72% pts; in 26% it was over 15.000. Primary tumor was localized in gonads (59%) and in sacrococcygeal region (30%). Following disease stages were identified: I and II--41% pts, III--34%, IV--25%. All patients were treated according to French TGM'95 protocol. 43 belonged to high risk and 52 to standard risk group. 77 children completed therapy, 15 continue treatment and 3 were lost from follow-up. RESULTS: Among children who were off therapy, 70 (91%) are alive in a complete remission (second remission in 3 cases). Survival in high risk group is 89%, while in standard risk group is 93%. Median time of follow-up is 31 months from the beginning of treatment and 25 months after completion of therapy. 7 children died; all had progressive disease. CONCLUSION: The outcome of malignant germ cell tumors treatment in Poland is favourable and comparable to results showed by other study groups in the world.

[Advances in the treatment of children with high risk acute lymphoblastic leukemia (ALL) treated with modified "NEW YORK" protocols between 1987 and 2002]. / Postepy w leczeniu dzieci z ostra bialaczka limfoblastyczna (ALL) wysokiego ryzyka wg modyfikowanych programów "NOWY JORK" w latach 1987-2002.

From 1981 to 1986, in children with ALL and initial WBC > or = 50,000/mm3, over 6-year disease-free survival was significantly lower (33%) than in children with WBC < 50,000/mm3 (60%). In attempt to improve this unsatisfactory results, three modified American protocols named: "New York", "New York I", and "New York II", "New York I", and "New York II" were introduced consecutively in the centers of Polish Pediatric Leukemia Lymphoma Study Group (respectively, in 1987, 1997, and 1999). The treatment results achieved in three consecutive therapeutic groups of children with ALL and initial WBC > or = 50,000/mm3: group I--213 children (1987-1996), group II--58 children (1997-1999), and group III--52 children (1999-2001) are presented. The observation was completed in December 31, 2002. In three evaluated groups the first complete remissions (CRs) were achieved in 90.6%. 94.8%. and 94.2% of patients, respectively. Relapses occurred in 71 patients of group I (37%), in 9 patients of group II (16%), and in 6 patients of group III (12%). The complications of treatment caused death in 7 children of group I, in 1 child of group II, and in 2 children of group III. Eighty-one (38%), 11 (18.9%), and 9 (17.3%) patients, respectively, died due to progression of disease. The event-free survival (EFS) in three evaluated groups did not depend on age of children and WBC. The rates of 2-, 5-, and 10-year event-free survival (EFS) in group I were: 69.9%, 55.3%, and 53.6%, respectively and the rates of 2- and 5-year EFS in group II were: 80.7% and 72.7%, respectively. The rate of 2-year EFS in group III was 71.6%. The analysis of achieved treatment results in three evaluated groups shows the gradual improvement of the prognosis in children with ALL and initial WBC > or = 50,000/mm3 treated with the use of modified protocols "New York" and "New York I" in comparison with patients treated before 1987. Longer observation is needed for evaluation of efficacy and complications of "New York II" protocol.