qPET - a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma.

BACKGROUND: Interim FDG-PET is used for treatment tailoring in lymphoma. Deauville response criteria consist of five ordinal categories based on visual comparison of residual tumor uptake to physiological reference uptakes. However, PET-response is a continuum and visual assessments can be distorted by optical illusions. OBJECTIVES: With a novel semi-automatic quantification tool we eliminate optical illusions and extend the Deauville score to a continuous scale. PATIENTS AND METHODS: SUVpeak of residual tumors and average uptake of the liver is measured with standardized volumes of interest. The qPET value is the quotient of these measurements. Deauville scores and qPET-values were determined in 898 pediatric Hodgkin's lymphoma patients after two OEPA chemotherapy cycles. RESULTS: Deauville categories translate to thresholds on the qPET scale: Categories 3, 4, 5 correspond to qPET values of 0.95, 1.3 and 2.0, respectively. The distribution of qPET values is unimodal with a peak representing metabolically normal responses and a tail of clearly abnormal outliers. In our patients, the peak is at qPET = 0.95 coinciding with the border between Deauville 2 and 3. qPET cut values of 1.3 or 2 (determined by fitting mixture models) select abnormal metabolic responses with high sensitivity, respectively, specificity. CONCLUSIONS: qPET methodology provides semi-automatic quantification for interim FDG-PET response in lymphoma extending ordinal Deauville scoring to a continuous scale. Deauville categories correspond to certain qPET cut values. Thresholds between normal and abnormal response can be derived from the qPET-distribution without need for follow-up data. In our patients, qPET < 1.3 excludes abnormal response with high sensitivity.

[Preliminary results of reproductive system function assessment in young men after Hodgkin's disease therapy]. / Wstepne wyniki oceny czynnosci ukladu rozrodczego mlodych mezczyzn z zakonczonym leczeniem choroby Hodgkina.

The introduction of modern methods of combined therapy: chemotherapy and radiotherapy, allows the cure more than 90% of children and adolescents with Hodgkin's disease (HD). However, the intensive treatment carries the risk of early and late complications. One of the late effects is gonadal dysfunction which may develop in men as well as in women. In this report preliminary results of testicular function assessment in young men after HD therapy. Testicular function was evaluated in 24 young men (age: 10.6-18.2 years, median 14.6 years at the beginning of treatment, and 18.5-24.6 years, median 21.4 years at the end of therapy) treated between January 1, 1999 and December 31, 2009. in Department of Pediatric Oncology and Hematology PAIP JU-CM in Kraków, according to PGP-HD-97 protocol. Multidrug chemotherapy combined with low-dose involved-field radiotherapy (15-25 Gy) was used in treatment in 21 men, and 3 other men were treated with chemotherapy only. Therapy was completed in all analyzed patients. Physical examination and Tanner stages of pubic hair and genital development were recorded as well as the plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (TST) were measured in all patients. Testicular volumes were measured in 14 men. The study was conducted between January 1, 2009 and December 31, 2009. All men reached Tanner stages of pubic hair and genital development appropriate for their age. One hundred and fourteen measurements of hormones levels were performed in all of patients. At least one abnormal result of measurements was found in 16/24 (66.7%) of men. The most frequent abnormality was the increased level of FSH (in 15 patients, 60.5% of FSH measurements). Abnormal results of measurements were found in 14/20 (70%) patients who received 6 chemotherapy cycles and in 2/4 patients treated with 3-4 cycles. Within the group of patients with abnormal results eight men previously received subdiaphragmatic region radiotherapy. Semen analysis was performed in one man and revealed azoospermia. Initial results of reproductive system assessment indicate the impairment of testicular function depending on intensity of treatment. Further observation and repeated gonadal function tests (including semen analysis) are needed in young men with completed HD treatment. These studies are essential especially for young people who intend to have children.

[Opsoclonus-myoclonus syndrome in children with neuroblastoma: description of 3 cases]. / Zespól opsoklonii mioklonii u dzieci z nerwiakiem zarodkowym wspólczulnym: opis trzech przypadków.

Neuroblastoma (NBL) is one of the most common childhood malignancies. Presence of untypical symptoms is characteristic for this malignancy; therefore it may mimic many other illnesses, both malignant and nonmalignant. Particular attention should be focused on opsoclonus-myoclonus syndrome (OMS, Kinsbourne's syndrome). In this paper three children with NBL previously diagnosed with OMS are presented. There is a need to test children with OMS for NBL as more than 30% of them are diagnosed with a tumor of neural origin. Children with NBL suffering from OMS have usually a favorable outcome with respect to their malignancy. However, the neurological and cognitive deficits are present for a long time and even they may become more intensive in spite of immunosuppressive therapy.

[Results of combined chemotherapy and local ophtalmic therapy for intraocular retinoblastoma]. / Wyniki chemioterapii skojarzonej z miejscowym leczeniem siatkówczaka wewnatrzgalkowego.

Until recently chemotherapy was used as adjuvant therapy after enucleation in cases with extraretinal spread of the disease (uveal extension, orbital extension, neoplastic infiltrates of the optic nerve at resection line, intracranial metastasis, generalized disease). Recent experience has proved that use of chemotherapy for intraocular retinoblastoma before local treatment (so called "chemoreduction") has allowed not only to decrease number of enucleations and indications for external beam irradiation or limit the extension of local therapy, but also increase chances for vision preservation and decrease the risk of severe complications. Seventy five children (with 106 involved eyes) aged 0.2 - 106 months with intraocular retinoblastoma diagnosed between January 1996 and June 2009 were the subject of this study. Among 106 involved eyes, in 70 (66%) the V stage according to Reese-Ellsworth classification (R-E) was established. Enucleation before chemotherapy was necessary in 9 (8.5%) cases, and in 22 more children the eye had to be removed after 1-2 courses of chemotherapy. In 68 remaining children (with 70 involved eyes) VEC (vincristine, etoposide, carboplatin) chemotherapy combined with delayed local therapy (cryotherapy, photocoagulation, brachytherapy) was employed. Out of 84 eyes treated by combined methods eye enucleation could be avoided in 47 (67%), including 18 (90%), 13 (87%) and 16 (46%) qualified to R-E group I-II, III-IV and V, respectively. First-line chemotherapy combined with the local treatment should be standard treatment for intraocular retinoblastoma groups I - IV. More effective therapy is required for R-E eye group V cases.

[Hemophagocytic syndrome in children with different underlying conditions]. / Zespól hemofagocytarny u dzieci w róznych jednostkach chorobowych.

Hemophagocytic syndrome (HS) is a life-threatening condition of hyperinflammation. Main symptoms are: prolonged fever, cytopenia, hepatosplenomegaly, hemophagocytosis, hyperferritinemia, hypertriglyceridemia and hypofibrinogenemia. Primary genetic form and secondary HS associated with infections, malignancies or autoimmune disorders can be distinguished. Untreated HS in most cases leads to death. We analyzed retrospectively 7 cases of HS in children (3 girls, 4 boys; aged 10 days -14 years) treated in 3 different pediatric centers from 2004 to 2009. In 3 cases HS was associated with infections (EBV, CMV, Bacillus Calmette Guerin - BCG), in 1 child with non-Hodgkin anaplastic large cell lymphoma (ALCL), in 1 patients probably with side effect of antiepileptic drug. In 2 cases cause of HS remained unknown. Fever, hepatomegaly, pan- or bicytopenia and hyperferritinemia were present in all children. In addition, splenomegaly was noted in 6 cases, hemophagocytosis in 6 children, impaired function or decreased number of NK cells in 4 cases, hypofibrino-genemia in 5 and hypotriglyceridemia in 4 patients. Among other symptoms and signs we observed: lymphadenopathy, hepatic failure, oedema, rash, neurological symptoms, increased level of LDH and inflammatory markers. In one child acute pancreatitis occurred. Among others, antibiotics, antiviral and immunosuppressive drugs were used in therapy. HLH-2004 protocol was applied in 4 cases. Patient with ALCL was treated with chemotherapy and allogeneic stem cell transplantation. Four patients are alive, 2 died because of HS, child with ALCL died because of generalized infection in peritrans-plantation period. In case of prolonged fever, splenomegaly and cytopenia diagnosis of HS should be considered. Following tests are recommended: complete blood count, ferritin, triglycerides, fibrinogen, bone marrow aspiration and NK cell assessment. Patients should be also screened for infections and malignancies. Early diagnosis of HS and underlying condition is crucial to start lifesaving therapy.

[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.

[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.

Genetic Signature of Acute Lymphoblastic Leukemia and Netherton Syndrome Co-incidence-First Report in the Literature.

The aim of the following case report is to provide a description of acute lymphoblastic leukemia (ALL) in a patient with Netherton syndrome (NS). A 15-year-old male with NS was referred with suspicion of acute leukemia. Severe anemia, leukocytosis, thrombocytopenia, and elevated CRP level were demonstrated in pre-hospital laboratory tests. Physical examination revealed generalized ichthyosiform erythroderma. ALL was diagnosed on the basis of bone marrow biopsy. The patient was initially classified as CNS3 status. No signals indicating fusion of BCR/ABL1, ETV6, and RUNX1 genes and MLL gene rearrangement were found in the cytogenetic analysis. The patient was qualified for chemotherapy and treated according to ALL IC-BFM 2009 protocol for high-risk ALL. During induction therapy, severe skin toxicity occurred (WHO grade III), which prompted the modification of treatment down to intermediate-risk strategy. In the course of reinduction therapy, severe chemotherapy-induced adverse drug reactions occurred, including progression of skin toxicity to WHO grade IV. The patient achieved complete remission. In view of life-threatening toxicities and the confirmed complete remission, intensive chemotherapy regimen was discontinued and maintenance treatment was started. Because of the baseline CNS3 status, the patient received cranial radiotherapy. Whole exome sequencing (WES) was used to identify disease-associated mutations. WES revealed two germline mutations: a novel premature termination variant in SPINK5 (p.Cys510*), along with a novel potentially pathogenic variant in NUP214 (p.Arg815Gln). Somatic mutations were known pathogenic variants of JAK2 (p.Arg683Gly), IL17RC (p.Ala303Thr), and potentially pathogenic non-synonymous variants of TTN (p.Gly1091Arg and p.Pro17245Leu), ACTN2 (p.Ile143Leu), TRPV3 (p.Arg729*), and COL7A1 (p.Glu2842fs) genes. Currently, the patient continues maintenance chemotherapy, with stable status of skin lesions and no features of ALL relapse. To our knowledge, this is the first report of ALL in a patient with NS. As has been presented, in such patients, optimal treatment according to the current protocols is extremely difficult. WES was used to confirm the diagnosis of Ph-like ALL in our patient. The detection of JAK2 gene mutation offers the possibility of therapy personalization. A specific signature of rare germline variants and somatic mutations can be proposed as a factor predisposing to the co-incidence of ALL and NS.

[Late complications of treatment for Hodgkin's disease in children and adolescents]. / Pózne powiklania po leczeniu choroby Hodgkina u dzieci i mlodziezy.

Based on our center's experience and data from literature we present the late complications of treatment in patients cured from Hodgkin's disease in childhood. The knowledge of the risk factors of side effects of treatment will allow to follow-up the patients effectively after cessation of therapy. The late complications may be life threatening (second cancers, severe organ damage) or be the cause of disability or impair the patient's quality of life. Reduction of rate of late complications in persons cured from Hodgkin's disease and other childhood cancers is a very important goal for pediatric oncologists.

[Recommendation for using granulocyte and granulocyte-macrophage growth factor during anti-cancer therapy in children]. / Rekomendacje stosowania granulocytarnych i granulocytarno-makrofagowych czynników wzrostu w przebiegu leczenia przeciwnowotworowego u dzieci.

Neutropenia is the most often side effect during antineoplastic treatment. In this article current recommendations for clinical applications of granulocyte and granulocyto-macrophage hematopoietic factors and possibility of protection of neutropenia, and its serious complications in pediatric oncology are presented.

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

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

[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.

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

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

[The health state evaluation in persons after therapy of Hodgkin's disease in childhood: report of the Polish Pediatric Leukemia/Lymphoma Study Group]. / Ocena stanu zdrowia osób z zakonczonym w dziecinstwie leczeniem choroby Hodgkina: raport Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków.

The introduction of modern methods of combined therapy: chemotherapy and radiotherapy, allows the cure more than 90% of children and adolescents with Hodgkin's disease. However, the intensive treatment may cause early and late complications. The late complications may include: damage of soft tissues and respiratory, cardiovascular, skeletal, and endocrine systems, and second cancers. Late complications may impair the patients' quality of life after cessation of therapy. This study presents evaluation of health status of persons who underwent therapy for pediatric Hodgkin's disease in centers of Polish Pediatric Leukemia/Lymphoma Study Group. The special questionnaire was established to collect data concerning hematopoietic system function, damage of soft tissues and skeletal system, thyroid and reproductive organs function, respiratory, cardiovascular, and nervous system function, liver and kidney function, status of dentition, occurrence of infections, immunologic system function, and psychological and social problems. The project included patients treated in 9 pediatric oncology centers. During the study the questionnaires of 288 patients [151 boys (52.4%) and 137 girls (47.6%)] in whom treatment of Hodgkins's disease started in 1994-1996 (44 questionnaires), and in 1997-2001 (244 questionnaires). In 42 patients no diagnostic procedures were performed. In this group 20 patients are currently under care of adult oncology clinics, 21 failed to come for a visit, and one patient is treated because of HD progression. The questionnaires of 246 patients treated in 1994-1996 (25 questionnaires) and 1997-2001 (221 questionnaires), were analyzed and the data on the late complications of these patients were obtained. General health status of examined patients was found satisfactory. However, 2.3% of patients had radiological evidence of pulmonary fibrosis, and 4.9% had various ECG abnormalities. Endocrine therapy is needed in 4.5% of patients because of thyroid function abnormalities. Second cancers were diagnosed in 1.7% of patients. The health status of children and adolescents cured from Hodgkin's disease and other childhood cancers should be regularly evaluated. Results of these evaluations will be the basis for introducing new treatment protocols aimed of decreasing the incidence of late complications while maintaining or improving cure rates.

[Preliminary results of thyroid function assessment in children and adolescents with Hodgkin's disease (HD) treated according to PGP-HD-97 protocol]. / Wstepne wyniki badania czynnosci tarczycy u dzieci i mlodziezy z choroba Hodgkina (HD) leczonych wedlug programu PGP-HD-97.

The intensive treatment of HD (multidrug chemotherapy combined with radiotherapy) carries the risk of early and late complications. One of the late effects is thyroid dysfunction which may occur after radiotherapy of the cervical region. In this report preliminary results of thyroid function assessment in children with HD in correlation with time after cessation of therapy are presented. Between January 1, 1997 and December 31, 2002, 58 children with HD (age: 2.6-18.3 years, median, 14.9 years) were treated in Department of Pediatric Oncology and Hematology PAIP CMUJ in Kraków, according to PGP-HD-97 protocol and these patients were included in the study. Multidrug chemotherapy combined with low-dose involved-field radiotherapy (15-25 Gy) was used in treatment of these children. Therapy was completed in all of analysed patients and in 38 of them (65.5%) at least 24 months before the end of observation. Physical and ultrasound examination of thyroid gland, and plasma levels of T3, T4, fT3, fT4, and TSH were measured before treatment of HD, before the treatment cessation, and every 6-12 months after the completion of therapy. The observation was completed on December 31, 2003. Six hundred and twelve measurements were performed in all of patients. At least one abnormal result of thyroid hormones or TSH levels was found in 50% of children. The most frequent abnormality was the increased level of TSH which occurred in 27.6% of patients. The rates of abnormal results of TSH concentration before HD treatment, and 1 year, 2 years, and later than 2 years after the cessation of therapy were: 8.3%, 8.8%, 21,4%, and 10.2%, respectively. These differences were not statistically significant. Seven patients (12%) require endocrinological treatment due to thyroid dysfunction. These patients as well as other analysed children are clinically euthyreotic. Initial results of thyroid function assessment presented in this report indicate that longer follow up and further thyroid function tests, physical and ultrasound examination of thyroid gland in patients after HD therapy cessation are needed. These studies are essential to early detection and adequate treatment of early and late complications of HD therapy.

[The assessment of efficacy of hepatitis B prophylaxis in children with acute lymphoblastic leukemia]. / Ocena skutecznosci profilaktyki wirusowego zapalenia watroby typu B u dzieci z ostra bialaczka limfoblastyczna.

The aim of the study was to evaluate the efficacy of hepatitis B prophylaxis in children with acute lymphoblastic leukemia (ALL) and to try to determine the optimal procedure of protection against the infection. The retrospective analysis included 229 patients with ALL divided into three groups depending on the type of anti-HBV prophylaxis. The group 1 (1990-91, 38 patients) received only sporadically passive prophylaxis, in the group 2 (1992-94, 55 patients) passive prophylaxis was regular, and the patients of the group 3 (1995-2001, 138 children) received complete active and passive prophylaxis. Among vaccinated children three subgroups were additionally distinguished: subgroup a--vaccination was completed before the disease, subgroup b--the cycle of vaccination began before and continued during the therapy, subgroup c--the whole cycle of vaccination was performed during the ALL treatment. The efficacy of the prophylaxis was evaluated taking into account the incidence of hepatitis B and the level of anti-HBs antibodies in vaccinated children. Additionally the incidence of hepatitis C was assessed to evaluate the role of unspecific prophylaxis. The incidence of hepatitis B in the group 1, 2, and 3 was: 57.9%, 23.6%, and 0.76%, respectively, and the incidence of hepatitis C: 44.7%, 36.4%, and 5.9%, respectively. The percent of the failure of active prophylaxis in the subgroup a, b, and c was: 29%, 53%, and 93%, respectively. In spite of the reduction of exposure to the infection (unspecific prophylaxis), the role of specific prophylaxis is essential. The program of passive and active prophylaxis used by us is efficient in preventing hepatitis B in children with ALL. However, during the intensive chemotherapy only passive prophylaxis should be used with postponement of the vaccination because of very low response to the vaccination applied in this phase of treatment. Regular control of anti-HBs antibodies' level is essential in all patients with leukemia even in those with initially high level of antibodies.

[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.

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

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

[Over 30-year experience of Polish Pediatric Leukemia/Lymphoma Study Group for treatment of Hodgkin's disease in children and adolescents: improvement curability and decrease of serious complications]. / Ponad 30-letnie doswiadczenie Polskiej Grupy ds. Leczenia Bialaczek i Chloniaków w leczeniu choroby Hodgkina u dzieci i mlodziezy: poprawa wyleczalnosci i zmniejszenie powaznych powiklan.

Currently over 90% of children with HD can be cured thanks to use of chemotherapy (CT) combined with involved field radiotherapy (IF-RT). From 1971 to 2001, 1062 children and adolescents with HD (stage I to IV) were treated in 10 oncological centers PPLLSG. Majority of patients were treated with CT combined with IF-RT. Year by year the intensity of therapy (CT and RT) was gradually adjusted to the risk-factor groups, and invasive methods of staging were also gradually limited. Supportive care was improved at the same time. Along with the modified therapy protocol, five consecutive periods of time (I: 1971-82; II: 1983-87; IIII: 1988-93; IV: 1994-96; V: 1997-2001) were analyzed. In the first period the basic CT was MVPP (mechlorethamine, vinblastine, procarbazine, prednisone), while later B-DOPA (bleomycin, dacarbazine, vincristine, prednisone, doxorubicin) was gradually introduced alone or alternately with MVPP. In order to decrease the incidence of late complications, the dose of IF-RT from 45 Gy to 15-30 Gy was reduced in the next periods. In V period in 21 children with stage IA and IIA with favorable prognostic factors, CT alone was used. The probability of over 5-year: overall survival, relapse free survival and event free survival were in the I period: 92%, 83% and 77%, in the II period: 97%, 92% and 89%, in the III period: 97%, 93% and 91%, in the IV period: 95%, 91% and 90%, in the V period: 95%, 95% and 93%. Decreased rate of serious complications was also observed. Intensity of therapy should be tailored to the stage of disease, and to other significant prognostic factors. The current strategy of diagnosing and treatment of HD is aimed at balancing between the highest possible cure rates and risk of late complications.

Iron deficiency and hematological changes in adult patients after Fontan operation.

BACKGROUND: Growing evidence indicates that iron-deficiency anemia is common in patients with congenital heart diseases. The aim of this study was to characterize hematologic changes and iron metabolism in adult Fontan patients. We also searched for the associations between these parameters and physical performance in the study group. METHODS AND RESULTS: Thirty-two white Fontan patients with a mean age of 25 ± 4.5 years and 30 healthy control subjects matched for age and sex were studied. Complete blood count together with iron-related parameters was determined in plasma of peripheral venous blood. The cardiopulmonary exercise test was performed. The Fontan patients had higher red blood cell counts (6.0 ± 2.1 × 10(9)/µl vs. 4.8 ± 0.4 × 10(9)/µl, p<0.001), hemoglobin (16.7 ± 1.4 g/dl vs. 14.2 ± 1.3g/dl, p<0.001), hematocrit (49 ± 3.4% vs. 42.1 ± 3.1%, p<0.001), red cell distribution width (RDW) (14.3 ± 2.4% vs. 12.8 ± 0.5%, p<0.001), while mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were similar in both the groups. Compared to the controls, the Fontan patients had higher unsaturated iron binding capacity (46.1 ± 12.6 µmol/l vs. 38.4 ± 11.9 µmol/l, p=0.02), total iron-binding capacity (62.8 ± 9.8 µmol/l vs. 57.8 ± 8.5 µmol/l, p=0.04), lower transferrin saturation (27.4 ± 11.4% vs. 34.6 ± 13.4%, p=0.03), and oxygen uptake, while iron and ferritin levels were comparable in both the groups. The multivariate model showed that SatO2 and cystatin C were independent predictors of RDW, and alanine aminotransferase was an independent predictor of ferritin level. Interestingly RDW was an independent predictor of oxygen uptake. CONCLUSION: Adult patients after Fontan operation despite having increased hemoglobin, hematocrit, and red blood cells have insufficient iron stores. Red cell distribution width is an indicator of iron deficiency in adult Fontan patients and it correlates with lower exercise capacity. Elevated ferritin levels in adult patients after Fontan surgery are associated with liver failure.