Invasive fungal infection of the central nervous system in a patient with acute myeloid leukaemia.

BACKGROUND: Although the new intensive chemotherapeutic programs introduced recently into hematooncological therapies have led to a higher number of recoveries, persistent neutropenia favours the spread of severe infections, frequently fungal infections. Systemic fungal infections in patients treated for proliferative diseases of the hematopoietic system are characterised by a severe, progressing course and high morbidity. CASE REPORTS: We present a case report that demonstrates the diagnostic problem of lesions in the central nervous system which developed following the fourth block of chemotherapy in an eight-year-old boy treated for acute myeloid leukaemia. The risk factors, high values of the inflammatory parameters and imaging results enabled us to diagnose a fungal infection of the central nervous system. RESULTS: A fast improvement in the clinical condition of the patient after the applied antifungal therapy and the regression of lesions in the central nervous system shown in the imaging studies confirmed our final diagnosis.

[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.

Concomitant EBV-related B-cell proliferation and juvenile myelomonocytic leukemia in a 2-year-old child.

We present a case of a 2-year-old girl, who developed concomitant EBV-related B-cell proliferation and juvenile myelomonocytic leukemia (JMML). JMML was initially not recognized because of predominant B-cell proliferation. The activating N-RAS mutation was retrospectively already detectable at this early stage. Our findings support the hypothesis that EBV may contribute to JMML pathogenesis by stimulating pre-existing malignant clones. However, such stimulation of leukemic clone does not require the direct incorporation of the virus into myeloid progenitors. Most probably a cytokine burst resulting from EBV infection allows expansion of pre-existing malignant myeloid progenitors. Further studies are required to delineate exact mechanisms of EBV-related promotion of the JMML clone.

[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.

[Langerhans cell histiocytosis in a child with congenital neutropenia]. / Histiocytoza z komórek Langerhansa u dziecka z wrodzona neutropenia.

Congenital neutropenia predisposes to the development of haematopoetic malignancies. We present a 3,5-year child, diagnosed with congenital neutropenia at the age of I month. The diagnosis was based on peripheral blood and bone marrow aspirate analyses, performed after the treatment of multiple axillar abscesses. Recurrent infections were treated with broad-spectrum antibiotics and leukocyte colony stimulating factors. At the age of 19 months during routine check-up the child presented with gingival hypertrophy, fragility and bleeding. The histopathological analysis of gingival biopsy was consisted with the diagnosis of Langerhans cell histiocytosis. The child was treated according to LCH protocol for therapeutic group C. After 12 months of such chemotherapy, the follow-up histopathological analysis of gingival biopsy revealed the presence of Langerhans cells, which was the indication for chemotherapy prolongation (6 additional VP courses). Chemotherapy was completed after 6 additional courses and the disease remission was confirmed by histopathological analysis of gingival biopsy. Congenital neutropenia predisposes to myeloproliferative disorders, particularly to childhood myeloblastic leukemia. Based on the presented case report we would like to emphasize the possibility of other hematological syndromes development.

[Sudden blindness of 11-year old boy in the course of acute lymphoblastic leukemia]. / Nagle zaniewidzenie u 11-letniego chlopca w przebiegu ostrej bialaczki limfoblastycznej.

PURPOSE: The aim of this study is to present dramatic ocular manifestation of acute lymphoblastic leukemia. MATERIAL AND METHODS: The 11 years old boy was hospitalized due to acute leukemia at the Department and Clinic of Pediatric Hematology, and was referred to ophthalmic examination because of sudden blindness of the right eye. General ophthalmic examination and electrophysiological tests were done. RESULTS: No light perception of right eye, and markedly reduced visual evoked responses were caused by infiltration with great edema in optic nerve and its surrounding of retina. In spite of the fact, that the infiltrations disappeared after general therapy, the vision did not recover at all. CONCLUSIONS: Even intensive treatment may be ineffective in blindness prevention in severe course of acute leukemia.

Concentration of IL-2, IL-6, IL-8, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia after cessation of chemotherapy.

The immunosuppressive effect of cytotoxic drugs, basic therapeutic agents in the treatment of childhood acute leukemias, requires monitoring of the immune system following cessation of therapy. The cytokines are soluble proteins that play a key role in the immunoregulation of the lymphocyte function. The cytokines regulate growth, differentiation and function of various cells in normal conditions. The aim of our study was to estimate serum levels of IL-2, IL-6, IL-8, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia (ALL) after cessation of chemotherapy. The study involved 150 children with ALL. This group consisted of: 30 children 1 month after treatment cessation; 30 children, 3 months later; 30 children 6 months later; 30 children, 9 months later and 30 children, 12 months later. The control group consisted of 30 healthy children. The levels of the cytokines under study were assayed using the immunoassay kits (R&D Systems, USA). During the study significant differences in TNF-alpha, IL-2 and IL-8 serum concentrations were observed among treated children and controls. However there were no differences in IL-6 and IL-10 concentrations.

[Acute endophthalmitis of 15-year old boy in the course of acute lymphoblastic leukemia--part I]. / Ostre zapalenie galki ocznej u 15-letniego chlopca w przebiegu ostrej bialaczki limfoblastycznej--czesc I.

PURPOSE: The aim of this study is to present dramatic ocular manifestation of acute lymphoblastic leukemia. MATERIAL AND METHODS: 15-year old boy was hospitalized due to acute leukemia at the Department and Clinic of Pediatric Hematology and was referred to ophthalmologist because of strong pain and decreased visual acuity of the left eye. General ophthalmic examination and electrophysiology were done. These procedures were repeated after 1, 2, 5 and 11 weeks and also after 6 and 9 months. RESULTS: Acute uveitis with cellular exudation to the vitreous, papilledema, swelling of the macula and green-yellowish infiltration which elevated the temporal part of the retina, were noticed. Swelling of the iris and miosis were observed. After one week of local anti-inflammatory treatment the eye became painless with little deep injection only. Simultaneously causal treatment of basic disease was continued. Control examinations revealed step by step improvement of ocular changes. After 6 months in the place of retinal infiltration choroidoretinal atrophy was seen. The functional deficits in visual field and electrophysiological examinations were found, too. One year later, the patient came again because of recurrence. Involvement of the central nervous system with signs of meningitis occurred. Visual acuity was normal and no infiltration of eyes was found, but there was papilledema in both eyes. CONCLUSIONS: In acute leukemia ocular manifestation may be highly expressed. The patients require local symptomatic and general causal treatment in cooperation of ophthalmologist with hematologist.

[Leukapheresis in children with chronic myeloid leukemia and pulmonary leukostasis]. / Leukafereza u dzieci chorych na przewlekla bialaczke szpikowa z objawami leukostazy plucnej.

We present two patients with chronic myeloid leukemia and hyperleukocytosis above 350 x 10(9)/l causing the symptoms of pulmonary leukostasis. Therapeutic leukapheresis procedures with concomitant chemotherapy were initiated within 12 hours from the diagnosis. After the therapy commencement the general condition of the patients systematically improved and leukocytosis gradually decreased from the second day of treatment with disappearance of pulmonary leukostasis symptoms. Thanks to application of such treatment procedures during the cytoreductive period, severe complications related to leukostasis could be prevented.