First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

Diagnosis and treatment of renal cell carcinoma in children: a report from the Polish pediatric rare tumor study group.

BACKGROUND: Renal cell carcinoma (RCC) in children is rare, accounting for approximately 1.9-6% of all pediatric renal malignancies. The aim of this study was to transmit our experience in the treatment of RCC in Polish children. METHODS: Clinical data from 21 children (6.3-18 years old) with RCC treated between 1992 and 2009 at Polish pediatric oncological centers were analyzed. RESULTS: In 2 patients, RCC developed as a second malignancy after neuroblastoma or astrocytoma fibrillare, respectively. In 6 patients, initial diagnoses based on imaging studies were unilateral Wilms' tumor, leading to preoperative chemotherapy. The remaining patients underwent surgery at the beginning of treatment. According to the AJCC/TNM staging system, 14 patients had stage I, 5-II, 1-III, and 1-IV. Nephrectomy was performed in 19 patients, heminephrectomy in one, and biopsy in another. Histopathological diagnoses were clear-cell RCC (18 patients), papillary RCC (2 patients), and chromophobe RCC (1 patient). 10 patients were treated with chemotherapy, with or without IL-2, INFα, and antiangiogenic agents. 2 patients died due to disease progression. CONCLUSIONS: RCC in children is mostly operable at diagnosis, resulting in good prognosis. The role of adjuvant chemo- and immunotherapies is unclear. Neoadjuvant chemotherapy proven for children with Wilms' tumors is ineffective, but the delay in adequate therapy did not worsen the outcome if complete nephrectomy is done subsequently.

Angiosarcoma in children - still uncontrollable oncological problem. The report of the Polish Paediatric Rare Tumours Study.

Angiosarcoma in children - still uncontrollable oncological problem. The report of the Polish Paediatric Rare Tumours StudyAngiosarcoma is a rare, highly malignant vascular neoplasm with little data available on its clinical course and management in children. Ten children with angiosarcoma (M/F: 6/4; aged 2, 3-16 years) registered in Polish Paediatric Rare Tumours and Soft Tissue Sarcomas Studies between 1992 and 2006. Primary tumour exceeded 5 cm in seven patients and affected mainly deep tissues (heart-2, head/neck, bladder, brain, liver and upper limb - one patient each). Four patients had regional and two metastatic diseases (lungs and bones). Three patients were initially misdiagnosed as haemangioma. Complete primary excision was unfeasible even in local stages. All patients received supplementing chemotherapy with no response in four. Radiotherapy was given to five children, including three after relapse. Three of five secondary tumour resections proved complete. Seven patients experienced relapses (mainly metastatic) and two continuous progression. Relapsed patients received chemotherapy +/- radiotherapy and surgery (three). Nine patients died of disease (overall survival 6-66 months), and one child after mutilating secondary resection is alive. Angiosarcoma in children is highly aggressive with an extremely poor prognosis. Complete primary excision is unfeasible, even in seemingly local stages. The response to chemotherapy is poor and the large number of metastatic recurrences suggests a need for systemic therapy modifications.

Remaining problems and controversies in the management of childhood head and neck soft tissue sarcomas: Retrospective (national) Multicenter Study of the Polish Pediatric Solid Tumors Group.

Soft tissue sarcomas in children are a heterogeneous group of malignant diseases. Among these, tumors localized in the head and neck region are especially difficult to treat. While multidisciplinary care has dramatically improved the prognosis of sarcoma patients, their treatment remains uncertain because of demand on radical surgical resection of the tumor. Achieving cure without deforming or mutilating the child remains the primary goal of treatment. This study is the multicenter (nationwide, 11 Polish centers) retrospective analysis of the treatment results in children having soft tissue sarcoma in the head and neck region during the previous decade (from 1991 to 2001). Late effects of the treatment are documented in long-term survivals. Eighty-five children from 1 to 212 months of age were included. Different multimodal treatment protocols were utilized (CWS-91, SIOP-MMT-91, and CWS-96). The median observation time was 25 months. Data on long-term effects were collected in 34 long-term survivals. Complete remission was achieved in 68 (80%) patients. Primary treatment failure occurred in 13 (15.3%) patients, all of whom succumbed in disease progression. Relapse occurred in 21 (30.9%) patients primarily achieving complete remission. Second primary neoplasm occurred in 3 children. The estimated 5-year event-free survival and the 5-year total survival rates for the whole group are 0.38 and 0.55, respectively. The main late effect documented in long-term survivals were cosmetic defects in 12 (35.3%) and visual field deficit or blindness in 8 (26.5%). Despite substantial improvement of the prognosis of pediatric soft tissue sarcomas, the multimodal treatment of head and neck region tumors remains controversial. Improved long-term outcome and focusing on psychosocial difficulties raise the important and difficult problem of functional results and cosmesis. Tumors localized in the orbit carry an excellent prognosis. However, the main late sequela is vision impairment and cosmetic defect due to the therapy given many years earlier. Two other tumor localizations--the parameningeal and nonparameningeal ones--still have bad prognosis. The observations made in this study confirm that main prognostic factors are the size of the primary tumor and the tumor stage. The worst prognosis remains invasive tumor (T2-stage) with a size over 5 cm. Individually adjusted multimodal therapy, which imperatively needs to be radical, though not mutilating, might minimize the late effects. Psychosocial problems in long-term survivors need to be focused on at the national level and better support must be provided in the future, involving a team of different medical and paramedical profiles.

Epidemiologic aspects and preventive strategy of hepatitis B and C viral infections in children with cancer.

AIMS: We present the efficacy of a strategy to control infections with hepatitis B (HBV) and C viruses (HCV) in children with cancer and assessment of risk for their relatives and health care personnel. A total of 1242 people entered the study, including 558 children with cancer, 193 relatives of infected children, 302 health care workers and 189 controls. METHODS: To stop dual HBV and HCV nosocomial infection in the oncology department, a preventive strategy was introduced. It involved immunoprophylaxis against HBV, screening blood donors for HCV infection, intensification of nonspecific prophylaxis, an educational program and estimation of risk for relatives of infected children and health care personnel. RESULTS: Retrospective analysis showed that the prevalence of HBV and HCV infections in children with cancer was 74 of 119 (62.2%) and 50 of 92 (54.3%), respectively, with the highest rate among patients with leukemia. Inferior anticancer therapeutic response were obtained in infected children. Specific anti-HBV immunoprophylaxis introduced simultaneously with anticancer therapy resulted in protection of 160 of 168 (95.2%) children in the first 4 years, when 62.9% of patients receiving therapy developed protective antibodies. Screening of blood donors and intensification of nonspecific prophylaxis reduced HCV prevalence to 2.8% during the most recent 1.5 years. Genotype analysis showed that the risk of HCV infection was 0.5% for relatives of infected children. The risk for health care personnel was 0 in the oncology ward and 1.9% in the other departments, and it reached 0.53% in control group. CONCLUSIONS: The preventive strategy of viral hepatitis in children with cancer, including passive-active HBV immunoprophylaxis from the beginning of chemotherapy and intensive nonspecific prophylactic measures is effective. With this strategy the risk of intrafamily and occupational infection is low.

[Usefulness of thoracic imaging and computed tomography in evaluation of neoplastic changes of lungs and mediastinum in children]. / Przydatnosc zdjecia przegladowego klatki piersiowej i tomografii komputerowej w ocenie zmian nowotworowych pluc i sródpiersia u dzieci.

Radiological methods of imaging diagnostics allow to evaluate exactly and to monitor the treatment course of pathological lesions in chest. Basic examinations are: plain chest X-ray and computer tomography. Optimal diagnostic algorithm of neoplastic changes in chest is not always univocally defined. The aim of the study is to compare the results of estimation of the presence and type of neoplastic changes in mediastinum and lungs based on X-ray and computer tomography. The results indicate that initial and control X-ray examination allows to diagnose mediastinal lymphadenopathy coexisting with pulmonary hilus extension. CT is used to diagnose and monitor lung tissue and mediastinal changes.

A nine-year experience of immunoprophylaxis against hepatitis B virus infection in children with cancer: results from a single institution in Poland.

The results of a nine-year study of immunoprophylaxis against HBV infection in children with cancer during anticancer therapy are presented. Three hundred and fifty-three children entered the study. The preventive strategy involved three different patterns of passive and active prophylaxis. Specific anti-HBV immunoprophylaxis introduced simultaneously with anticancer therapy resulted in protection of 95.2% of children; 62% of patients produced antibodies. Long-term follow-up confirmed stable protection. Better results were obtained in children who received the last dose of vaccine after chemotherapy. The overall infection rate was 5.4% (19/353). Thirteen (68.4%) of the 19 infections occurred in patients who had not received hepatitis B immunoglobulin at the beginning of anticancer therapy. Children vaccinated before chemotherapy (during a neonatal vaccination programme) showed continuous protection after one dose of vaccine in 94% cases. In three cases, both HBsAg and anti-HBs was observed. A preventive strategy for viral hepatitis in children with cancer that includes passive and active HBV immunoprophylaxis from the beginning of chemotherapy is effective.

[Treatment regimen for children and adolescents with Hodgkin's disease designed to decrease late complications of radiotherapy]. / Program leczenia choroby hodgkina u dzieci i mlodziezy zmierzajacy do ograniczenia powiklan po radioterapii.

Between 1997 to 1999 in 9 centres of the Polish Paediatlic Leukemia/Lymphoma Study Group, 167 children and adolescents (aged 2-19 years) with stage 1 to IV Hodgkin's disease (HD) were treated according to a regimen with a limited use of radiotherapy (RT). All patients received B-DOPA and MVPP chemotherapy. The number of cycles of chemotherapy was adjusted in respective risk groups. In 13 children with stage IA and IIA disease with favourable prognostic factors chemotherapy alone was used. In other patients the dose of RT applied to lymphatic regions was 15-46,4 Gy. In case of a small tumour at presentation and good response to initial chemotherapy the RT dose was 15-16 Gy. In other cases doses of 25-30 Gy were planned. The use of higher doses, particularly exceeding 35 Gy, in eleven patients, was not justified. Among all the 167 patients, three oftliem (1.2%) with advanced disease (Stage III-1V) did not achieve first remission. The 4-year overall survival (OS), relapse free survival (RFS) and event free survival (EPS) were 99%. 93% and 90%, respectively. Relapses occurred in 8 children (first remission lasted for 4-29 (median = 9 months). All 13 children in whom chemotherapy alone was used remain in first remission. In the group of children who received RT in the dose of 15-16 Gy relapse occurred in one child. Our preliminary analysis indicates that limited use of RT in selected cases of HD in children and adolescents did not show worse results of treatment. However, the assessment of possible influence of this regimen on the decreased rate of late complications requires longer follow-up.

Venoocclusive liver disease (VOD) as a complication of Wilms' tumour management in the series of consecutive 206 patients.

UNLABELLED: In 4 years (1993-1996) 206 pts. with nephroblastoma were treated. All children were treated according to SIOP 93-01 protocol. Overall survival was 92%. In 27 cases hepatotoxic events occurred. In 10 cases, venoocclusive liver disease (VOD) was diagnosed. VOD is a syndrome associated with hepatomegaly, sudden weight gain or ascites and jaundice. It results from damage to the endothelium of hepatic venules and necrosis of central hepatocytes with subsequent proliferation of fibrous tissue and occlusion of the central hepatic veins. Dactinomycin is one of the drugs considered responsible for its development. Mean age of VOD patients was 4 yrs, however 3 of them were below 1 yr. In all cases, VOD occurred during postoperative chemotherapy (mean 16 th week of treatment). All patients received dactinomycin and vincristine. Five children with right kidney tumors underwent post-operative abdominal irradiation. Main VOD symptoms were hepatomegaly and ascites (80%). Hypertransaminasaemia, as well as, on ultrasound, gallbladder wall thickening and/or free abdominal fluid were observed. Median VOD duration was 27 days and its course was usually temporary and self-limiting. However, in 2 cases recurrent VOD episodes were noted. All children received supportive treatment only. In 6 cases, VOD resulted in chemotherapy delay or drug reductions, while in 4 others chemotherapy was completed preliminarily. Nevertheless it did not affect patients' outcome overall survival in VOD group was 90%. CONCLUSIONS: Total 5% VOD frequency is similar to other reports. Infants and children receiving abdominal irradiation seem to be at special risk of VOD development.

[Adverse reactions associated with the use of L-asparaginase during therapy of patients with nB non-Hodgkin's lymphoma. Report of the Polish Paediatric LeuKaemia/Lymphoma Study Group]. / Objawy niepozadane leczenia preparatami L-asparaginazy u chorych z nieziarniczym chloniakiem zlosliwym typu NB w oparciu o material Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków Zlosliwych u dzieci.

The aim of the study was to determine the side effects of asparaginase administration during treatment protocol for childhood non-Hodgkin's lymphoma (NHL). Drug adverse reactions occurred in 20/66 of patients (30,3%) treated in 9 centres in Poland between 1993 and 1998. The most common side effects were coagulation disturbances in 12/66 of the children (18,2%), which occurred due to reduced production of important coagulation factors. Six patients (9,1%) developed impairment of liver function (9,1%). Drug toxicity caused the modifications of treatment protocol in 12/66 (18,2%) of patients, mainly in the induction phase; 3 children died due to relapse of disease.

[Results of the treatment of myelodysplastic syndrome (MDS)obtained by the Polish Paediatric Leukaemia /Lymphoma Study Group]. / Wyniki leczenia zespolów mielodysplastycznych (MDS) uzyskane przez Polska Pediatryczna Grupe ds Leczenia Bialaczek i Chloniaków u dzieci.

Sixty children with MDS treated in six centres of the Polish Paediatric Leukaemia/Lymphoma Study Group in the period 1975-1999 were included in the study. In 20 children RAEB-T, in 13 RA, in 21 RAEB and in 6 CMML were diagnosed. Our own and literature data showed that BMT is the best therapy for children with MDS. We need a new comprehensive protocol for the diagnosis and treatment of children with MDS in Poland.

[Abdominal presentation of B-cell non-Hodgkin's lymphoma (B-NHL) - surgical treatment and its results. Report of the Polish Paediatric Leukaemia/Lymphoma Study Group]. / Manifestacja brzuszna chloniaka B-komórkowego u dzieci - interwencja chirurgiczna i wyniki leczenia. Raport PPGLBC.

The aim of this study was to analyse the effect of LMB-89 protocol and surgical procedure at initial laparotomy on the outcome in children with abdominal B-cell NHL. The initial surgery intervention was: complete resection (20% pts), subtotal resection (20%), partial resection (4%), biopsy (36%). Postoperative complications occurred in 5 children. Complete recovery (CR) was achieved in 92% pts. There were 4% non responder patients. Two patients died before CR evaluation (tumour lysis syndrome; bleeding and multi organ failure after initial surgery). One patient died in CCR from sepsis probably influenced by the previous local operation. 10.8% patients relapsed. The estimate EFS for all patients with AB-NHL is 81%, 85% for stage III and 73% for stage IV. Major surgery in advanced stages is not recommended since it delays chemotherapy and fails to improve overall survival.

[Cardiotoxic complications in Wilms' tumour survivors after treatment with anthracyclines]. / Powiklania kardiotoksyczne u pacjentów z guzem Wilmsa leczonych antracyklinami.

The aim of the study was an evaluation of circulatory system functions in patients with Wilms' tumour who underwent the multidrug chemotherapy with anthracyclines. The investigation was carried out on 43 patients after chemotherapy between 1994-1997, from 4 centres of paediatric oncology (in Gdansk, Poznan, Lublin and Bydgoszcz). All patients were divided into two groups. The children from the first group received anthracyclines without Cardioxan protection. The patients from the second group had been treated with both anthracyclines and Cardioxan. The cardiotoxicity was estimated in relation to the total dose of anthracyclines. Comparing the side effects of chemotherapy in both groups there were no essential differences in bone marrow suppression and in hepatotoxic symptoms.

[The lack of parental acceptance of the stress associated with neoplastic disease of the child as a cause of treatment failure]. / Brak akceptacji rodziców wobec stresu zwiazanego z choroba nowotworowa dziecka jako przyczyna zaniechania leczenia.

Three unsuccessful cases of neoplastic diseases in children were described. No parents cooperation with treatment center led after good initial response to the progression of disease and the death of children. The reason of such parents' decisions was incapability to manage the stress caused by child's disease.

[The efficacy of G-CSF and GM-CSF in the adjunctive treatment of infections complicating chemotherapy of acute leukemia in children]. / Skutecznosc G-CSF i GM-CSF w leczeniu wspomagajacym zakazen wiklajacych chemioterapie ostrych bialaczek u dzieci.

Growth factors (G-CSF Neupogen Roche i GM-CSF Leucomax Sandoz) have been applied in 133 therapeutic and prophylactic cycles in 88 children with acute leukaemias. GM-CSF and G-CSF were administered subcutaneously or intravenously at a dose of 2 to 8 micrograms/kg for 2 to 28 days. 45 prophylactic cycles had been administered in children with acute lymphoblastic leukaemia in high risk group and in relapses, which caused significant reduction in the number of infections, time of neutropenia and fever. Therapeutic cytokines cycles were applied when the absolute neutrophil count have fallen below 0.5 x 109/l. We observed significant reduction in duration of neutropenia in these cycles. Tolerance of GM-CSF and G-CSF was good. Side effects were not observed.

[Study on behavior of thyroid gland hormones in Bydgoszcz province children and teenagers with simplex struma]. / Badania nad zachowaniem sie hormonów tarczycy u dzieci i mlodziezy województwa bydgoskiego z rozpoznanym wolem prostym.

Struma caused by iodine deficit is an endemic disorder in specified regions. The purpose of the study was a biochemical characteristic of struma simplex in children from Bydgoszcz province and evalued correlation between laboratory exponents of thyroid gland function, size of the gland and kind of the struma. It was confirmed that neutral struma of children generally takes a course with euthyroidism. In children with struma were confirmed significant lower values of T4 and no significant higher values of T3. Value of TSH was no different in comparison with the control group. Proved was that hormonal thyroid activity is lower when struma is getting bigger.

[Estimation of effectiveness of antiemetic treatment with Zofran given in one dose to children with neoplasms]. / Ocena skutecznosci leczenia przeciwwymiotnego Zofranem podawanym w jednorazowej dawce dziennej dzieciom z choroba nowotworowa.

Clinical studies of antiemetic treatment with Zofran in children suffering from neoplastic diseases are presented. The studies were carried out in 33 children aged 3 months to 17 years treated in 1993. The majority of the patients were treated for ALL (20), Hodgkins disease (3), nephroblastoma (3), non-Hodgkin lymphoma (2), solid tumors (5). Two-hundred thirty-eight cycles of chemotherapy with cystostatics having varied emetic effects were carried out in these children. Zofran was given in one dose, one hour before chemotherapy in a dose of 4 or 8 mg. The intensity of vomiting was assessed according to the WHO 5-grade scale. O to 1 grade of vomiting was observed in 84.4%, 2nd grade in 15.2%. There were no cases of 3rd or 4th grade vomiting. No side-effects of the medication were observed in the studied group. It was found that Zofran is an effective and well-tolerated antiemetic medication in children on chemotherapy.

[Efficacy of passive and active immunization against HBV infection in children with neoplastic diseases]. / Skutecznosc bierno-czynnej immunizacji przeciw HBV u dzieci z chorobami nowotworowymi.

The efficacy of 3 schemes of passive and active prevention of HBV infection was evaluated in 47 children with haematologic proliferative diseases. Twenty-six children suffering from leukemia (group I) received passive immunisation (hepatitis B immunoglobulin) in six week intervals during intensive chemotherapy and were vaccinated on maintenance therapy. Thirteen children with Hodgkin or B-non-Hodgkin lymphoma (group II) received active immunisation from the beginning of intensive chemotherapy with two doses of immunoglobulin. Eight children who had completed their therapy (group III) were vaccinated only. Among children who completed vaccinations, 5/8 in group I, 4/7 in group II and 5/5 in group III produced protective anti-HBs levels. Passive/active prophylaxis was successful in most patients suffering from neoplastic diseases and reduced the endemy of HBV infection in our department from 43.3% to 2.56% infected subjects. Among 7 patients vaccinated from the beginning of treatment (group II), 4 of them produced protective levels of anti,-HBs, despite intensive chemotherapy.

[Fever in children with hematologic neoplastic diseases and implanted Broviac-Hickman catheters]. / Goraczka u dzieci chorych na nowotwory krwi z wszczepionymi cewnikami Broviaca-Hickmana.

A safe and effective method of venous access is important in the care and treatment of patients with malignancies. Thirty-seven Broviac-Hickman catheters were inserted in 32 children with haematological neoplastic disease. The mean indwelling time of the catheters was 7014 days. The catheters were used to administer chemotherapy and other drugs, blood products, and as well as to draw blood. Fever occurred 96 times. Forty-three percent of fever episodes were related to clinically documented infections and in 15% of cases, to catheter-related bacteremia caused by Gram-positive and Gram-negative strains in equivalent proportions. Fever was observed with a two fold greater incidence in patients with severe granulocytopenia (< 0.5 G/l).

[Preliminary evaluation of adverse effects after administration of arabinoside cytosine (Ara-C) in high doses to children with acute myelogenous leukemia]. / Wstepna ocena objawów niepozadanych po podaniu arabinozydu cytozyny (Ara-C) w duzych dawkach dzieciom z ostra bialaczka mieloblastyczna.

Five children with AML were treated with high-doses of Ara-C (2 g/m2) during consolidation. After 17 cycles the toxicity was evaluated. Granulocytopenia (< 0.5 x 10(9)/l) and thrombocytopenia (< 25 x 10(9)/l) were stated after 15/17 and 13/17 cycles respectively. The nadir of bone marrow suppression appeared between day 10 and 14. In one case treatment related death during severe myelosuppression was noted. In individual cases jaundice with elevated activity of aminotransferases, paralytic ileus and pulmonary oedema were observed. All these adverse reactions were reversible. Other toxicities such as nausea/vomiting, stomatitis, diarrhea, infections and drug related fever were transient. No neurologic toxicity was seen. There is a need for developing a new way of the administration of high-dose Ara-C which could substantially reduce toxicity of the drug.