A hagyományos citogenetika és a FISH egymást jól kiegészítő vizsgálatok gyermekkori akut limfoid leukémiában

Primary genetic abnormalities of leukemia cells have important prognostic significance in childhood acute leukemia. In the last two years 30 newly diagnosed or recurrent childhood ALL bone marrow samples were analyzed for chromosomal abnormalities with conventional G-banding and interphase-fluorescence in situ hybridization (I-FISH) using probes to detect BCR/ABL fusions, cryptic TEL/AML1 and MLL rearrangements and p16(9p21) tumor suppressor gene deletions. G-banded karyotype analysis found clonal chromosomal aberrations in 50% of cases. With the use of complementary I-FISH techniques, ALL-specific structural and numerical changes could be identified in 70% of the patients. Nine cases (30%) had subtle chromosomal aberrations with prognostic importance that had not been detected in G-banded analysis. Conventional G-banding yielded additional information (rare and complex structural aberrations) in 19% of patients. The most common aberration (30%) was AML1 copy number increase present in G-banded hyperdiploid karyotype as a chromosome 21 tetrasomy in the majority of cases; one case displayed 5-6 copies and in another case amplification of AML1 gene on der(21) was combined with TEL/AML1 fusion of the homologue AML1 gene and deletion of the remaining TEL allele. High hiperdiploidy was detected in 6 cases, in one patient with normal G-banding karyotype. TEL/AML1 fusion signals were identified in four patients. Deletion of p16 locus was found in eight cases (23%), of which only two had cytogenetically visible rearrangements. G-banding in combination with I-FISH has produced major improvements in the sensitivity and accuracy of cytogenetic analysis of ALL patients and this method helps to achieve a more precise identification of different risk categories in order to choose the optimal treatment

Rheumatic symptoms in childhood leukaemia and lymphoma-a ten-year retrospective study

Background: The initial symptoms of childhood leukaemia and lymphoma are often similar to those of juvenile idiopathic arthritis (JIA). In our study, we analyzed the frequency and characteristics of musculoskeletal complaints as the initial presenting symptoms of newly diagnosed leukaemia and lymphoma patients in the past 10 years in our clinic. Methods: Using the Hungarian Tumour Register, we performed a retrospective analysis of the medical records of 166 new leukaemia and 95 new lymphoma pediatric patients treated from 1999 to 2009 at the 2nd. Dept. of Paediatrics of the Semmelweis University in Budapest. Results: Twenty percent of the leukaemic (33 children) and 2% of the lymphoma patients (2 children) had musculoskeletal symptoms at first presentation. Two-thirds of both groups of patients had other general symptoms like fever and/or fatigue. The hip was the most frequently affected joint (7/33) in the leukaemic patients. Twenty-four percent of all the children had been previously evaluated by an orthopaedist; 12% had visited another rheumatologist prior to diagnosis. Imaging had been done in an unexpectedly low number of patients prior to referral to our unit (radiographs: 16 or 48%, ultrasound: 5 patients or 15%). Radiographs of the affected joints were abnormal in only one case (1/16, 6%). The joint ultrasound was abnormal in only three children of 5 studied (3/5, 60%). Anaemia (26/32, 6%), thrombocytopenia (78%) and LDH elevation (3-4 times the normal count) were frequent in the leukaemic patients. Half of the cases had a normal leukocyte count. The lymphoma group had similar results. Two patients of the leukaemia group received steroid treatment before the final diagnosis. Severe pain out of proportion to physical findings is another clue. Conclusions: Haematologic malignancies must be excluded before initiation of therapy for childhood arthritis among children presenting with musculoskeletal signs and symptoms, particularly in atypical cases. Malignancies are to be suspected when pain is disproportionately severe compared to the physical examination findings, and when anaemia, thrombocytopenia, and an elevated LDH level are present. Diagnosing leukaemia early is important because the use of steroids and immunosuppressive medications may mask and delay its diagnosis. Additionally, pre-treatment of presumed JIA patients with these drugs who eventually are diagnosed to have a malignancy may lead to the malignancy being steroid-resistant and more difficult to treat

Primary alveolar rhabdomyosarcoma of the bone: two cases and review of the literature

BACKGROUND: Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin and comprises the largest category of soft-tissue sarcomas both in children and adolescents. From a pediatric oncology point of view, RMS has traditionally been classified into alveolar (ARMS) and embryonal (ERMS) subtypes. The anatomical localization of the tumor may vary, but commonly involve the head/neck regions, male and female urogenital tract or the trunk and extremities. CASE PRESENTATION: Here, we report two challenging cases involving 17- and 9-years-olds males where diffuse and multiplex bone lesions suggested either a hematological disease or a primary bone tumor (mesenchymal chondrosarcoma). Biopsies, proved a massive infiltration of the bone marrow cavity with rhabdomyosarcoma. In both cases, the ARMS subtype was confirmed using FOXO1 break-apart probes (FISH). Radiological examination could not identify primary soft tissue component in any localization at the time of diagnosis in either cases. CONCLUSIONS: Primary alveolar rhabdomyosarcoma of the bone as a subtype of ARMS, seems to be a distinct clinico-pathological entity with challenging diagnostic difficulties and different, yet better, biological behavior in comparison to soft tissue ARMS. However, it is difficult to be characterized or predict its prognosis and long-term survival as only sporadic cases (four) were reported so far

Effective BRAF inhibitor vemurafenib therapy in a 2-year-old patient with sequentially diagnosed Langerhans cell histocytosis and Erdheim-Chester disease

Erdheim–Chester disease (ECD) is a rare histiocytic disorder, characterized by the xanthomatous infiltration of tissues by CD68-positive and CD1a-/CD100-negative foamy histiocytes. In childhood, ECD is exceptionally rare, and only a dozen cases have been published so far. The cooccurence of Langerhans cell histiocytosis (LCH) and ECD is even rarer. Here, we report a 2-year-old boy, the youngest patient in the literature so far, who was diagnosed with concomitant BRAF mutation-positive LCH and ECD. In his case, conventional LCH treatment proved to be ineffective, but he is the youngest patient who was successfully treated with the BRAF inhibitor vemurafenib

Lágyrészszarkómás gyermekek kezelési eredményei a Semmelweis Egyetem II. Sz. Gyermekgyógyászati Klinikáján

Malignant tumors found in children are different from the ones that occur in adults. Compared to the malignancies in adults, the histological entities in pediatric patients are different and survival rates are higher among the children. Though pediatric soft tissue sarcomas are less common than leukemia and central nervous system malignancies, recognition of them is necessary to start the therapy as soon as possible. The delay of an appropriate treatment - chemotherapy, radiotherapy, surgery, in some cases targeted therapy - is unfavorable because somatic damages and functional loss can occur. In our study at the oncology department of the 2nd Department of Pediatrics of Semmelweis University, we collected and analyzed the data of 90 children who were diagnosed with soft tissue sarcomas between January of 2000 and November of 2016. Our results correlate with the data collected worldwide

Nagy dózisú methotrexatkezelések farmakokinetikai vizsgálata gyermekkori hematológiai malignitásokban

Monitoring the pharmacokinetic parameters of different anticancer drugs is necessary because they might have several side effects. Aim: Pharmacokinetic and toxicity evaluation of high-dose methotrexate treatments in children with acute lymphoblastic leukemia. Patients and methods: 43 children (28 boys, 15 girls, mean age: 7.03 years) in 147 cases were treated with 5 g/m2/24h MTX according to ALL-BFM 1995 and 2002 protocols. Methotrexate and 7-hydroxi-methotrexate levels were measured with high pressure liquid chromatography at 24, 36, 48 hours. Authors registered the development of hepatotoxicity, nephrotoxicity, grade III/IV oral mucositis. Results: Therapeutic methotrexate serum concentrations (30-100micromol/l) were achieved in 72.5% of the cases. Repeated treatments resulted similar serum levels. Hepatotoxicity and hypoproteinemia occurred in 17% and in 48.9% of the cases. There was significant correlation between serum 7-hydroxi-methotrexate and creatinine levels (p<0.05). Conclusion: 5 g/m2 methotrexate resulted reliable therapeutic serum levels with mild and reversible toxicity. 7-hydroxi-methotexate measurements might be more useful than methotrexate levels to detect toxicity. Orv. Hetil., 2011, 152, 1609-1617

High-Grade Osteosarcoma of the Foot: Presentation, Treatment, Prognostic Factors, and Outcome of 23 Cooperative Osteosarcoma Study Group COSS Patients

Osteosarcoma of the foot is a very rare presentation of a rare tumor entity. In a retrospective analysis, we investigated tumor- and treatment-related variables and outcome of patients registered in the Cooperative Osteosarcoma Study Group (COSS) database between January 1980 and April 2016 who suffered from primary high-grade osteosarcoma of the foot. Among the 23 eligible patients, median age was 32 years (range: 6-58 years), 10 were female, and 13 were male. The tarsus was the most commonly affected site (n=16). Three patients had primary metastases. All patients were operated: 5 underwent primary surgery and 18 received surgery following preoperative chemotherapy. In 21 of the 23 patients, complete surgical remission was achieved. In 4 of 17 patients, a poor response to neoadjuvant chemotherapy was observed in the resected primary tumors. Median follow-up was 4.2 years (range: 0.4-18.5). At the last follow-up, 15 of the 23 patients were alive and 8 had died. Five-year overall and event-free survival estimates were 64% (standard error (SE) 12%) and 54% (SE 13%), which is similar to that observed for osteosarcoma in general. Event-free and overall survival correlated with primary metastatic status and completeness of surgery. Our findings show that high-grade osteosarcoma in the foot has a similar outcome as osteosarcoma of other sites

Prognostic Factors in Childhood Anaplastic Large Cell Lymphoma: Long Term Results of the International ALCL99 Trial

With the aim of describing the long-term follow-up and to define the prognostic role of the clinical/pathological/molecular characteristics at diagnosis for childhood, adolescent and young adults affected by anaplastic large cell lymphoma (ALCL), we analyzed 420 patients aged up to 22 years homogeneously treated within the international ALCL99 trial. The 10-year progression free survival (PFS) was 70% and overall survival was 90%, rare late relapses occurred but no secondary malignancies were reported. Among clinical/pathological characteristics, only patients presenting a small cell/lymphohistiocytic (SC/LH) pattern were independently associated with risk of failure (hazard ratio = 2.49). Analysis of minimal disseminated disease (MDD), available for 162 patients, showed that both SC/LH pattern (hazard ratio = 2.4) and MDD positivity (hazard ratio = 2.15) were significantly associated with risk of failure in multivariate analysis. Considering MDD and SC/LH results, patients were separated into three biological/pathological (bp) risk groups: a high-risk group (bpHR) including MDD-positive patients with SC/LH pattern; a low-risk group (bpLR) including MDD-negative patients without SC/LH pattern; and an intermediate-risk group (bpIR) including remaining patients. The 10-year PFS was 40%, 75% and 86% for bpHR, bpIR and bpLR, respectively (p 0.0001). These results should be considered in the design of future ALCL trials to tailor individual treatments