| 1. |
- Abd, Hadi, et al.
(författare)
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Ante mortem diagnosis of amoebic encephalitis in a haematopoietic stem cell transplanted patient
- 2009
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 41:8, s. 619-622
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Acanthamoeba species are widely distributed free-living amoebae showing an increased role as human pathogens causing encephalitis, keratitis, pneumonitis and dermatitis. A haematopoietic stem cell transplanted (HSCT) patient developed purulent meningitis while awaiting regrafting. The meningitis was thought to be an endogenous infection arising from the mucous membranes primarily involving the cervicofacial regions, probably due to haematogenous spread facilitated by surgery. We diagnosed a fatal case of granulomatous amoebic encephalitis caused by Acanthamoeba castellanii by direct microscopy of a cerebrospinal fluid sample (CSF), Acanthamoeba cultivation, Giemsa staining, polymerase chain reaction and sequencing.
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| 2. |
- Andreasson, Patrik, et al.
(författare)
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Cytogenetic and FISH studies of a single center consecutive series of 152 childhood acute lymphoblastic leukemias
- 2000
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 65:1, s. 40-51
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Tidskriftsartikel (refereegranskat)abstract
- Between 1977 and 1996, cytogenetic investigations were performed on 182 childhood (< or = 16 yr) acute lymphoblastic leukemias (ALL), constituting 94% (182 of 194) of all ALL patients diagnosed and treated at the Departments of Pediatrics, Lund and Malmo University Hospitals, Sweden, during these two decades. The cytogenetic analyses were successful in 152 cases (84%). The failure rate was higher for the ALL investigated before 1987 (30% vs. 4%, p < 0.0001), and also the incidence of cytogenetically normal cases was higher during 1977-86 (43% vs. 25%, p < 0.05). Clonal chromosomal abnormalities were found in 103 (68%) ALL. Structural rearrangements were detected, by chromosome banding alone, in 76 cases (50%). Fluorescence in situ hybridization (FISH) was used to identify cases with t(12;21), 11q23 rearrangements, and 9p deletions, using probes for ETV6/CBFA2, MLL, and CDKN2A/B, in 72 cases from which cells in fixative and/or unstained metaphase preparations were available. In total, the most common structural rearrangements were del(9p) (17%), t(12;21) (15%), del(6q) (8%), and MLL rearrangements (4%). Six (32%) of nineteen cytogenetically normal ALL analyzed by FISH harbored cryptic abnormalities; three displayed t(12;21) and four had del(9p), one of which also carried a t(12;21). Five (45%) of the t(12;21)-positive ALL showed +der(21)t(12;21) or ider(21)(q10)t(12;21), resulting in the formation of double fusion genes. Among the more rare aberrations, eight structural rearrangements were identified as novel recurrent ALL-associated abnormalities, and nine cases harbored rearrangements previously not reported. Sixteen cases displayed karyotypically unrelated clones at different investigations. Seven ALL (5%) showed simple chromosomal changes, unrelated to the aberrations detected at diagnosis, during morphologic and clinical remission, and in all but one instance the patients remained in remission, with the abnormal clone disappearing in subsequent investigations. This indicates that the emergence of novel clonal chromosomal aberrations during remission in childhood ALL is rather common and does not by necessity predict a forthcoming relapse.
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| 3. |
- Békássy, Albert, et al.
(författare)
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Arterial occlusion due to Listeria meningoencephalitis in an immunocompromised boy
- 1987
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 19:4, s. 485-489
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Tidskriftsartikel (refereegranskat)abstract
- Sequential CAT scan studies of the brain were performed in a 7-year-old boy with Listeria monocytogenes serotype 1 meningoencephalitis. The infection occurred while he was receiving maintenance chemotherapy for T-cell non-Hodgkin lymphoma. A lesion in the right hemisphere during the infection resulted in an excessive enlargement of the right ventricle 10 months later, most probably caused by arterial occlusion.
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| 4. |
- Békássy, Albert, et al.
(författare)
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Erwinase-induced pancreatitis
- 1992
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Ingår i: The Lancet. - 1474-547X. ; 340:8834-8835, s. 1552-1553
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Békássy, Albert, et al.
(författare)
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Fulminating clostridial septicemia in children treated for lymphoproliferative disorders
- 1984
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Ingår i: Scandinavian Journal of Infectious Diseases. - 1651-1980. ; 16:2, s. 157-159
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Tidskriftsartikel (refereegranskat)abstract
- Overwhelming Clostridium septicum infection in 2 children, 1 and 4 yr old, with acute lymphoblastic leukemia and B-cell non-Hodgkin malignant lymphoma, respectively, as well as fatal C. perfringens infection in a 3-yr-old child with histiocytosis-X are reported. A neutropenic patient with fever, abdominal symptoms and hypotension--but otherwise being well--must be suspected of having clostridial disease. The most alarming feature is shock and rapid course.
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| 6. |
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| 7. |
- Békássy, Albert, et al.
(författare)
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Hepatocellular carcinoma
- 1994
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 83:2, s. 150-150
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Békássy, Albert, et al.
(författare)
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Hepatocellular carcinoma associated with arteriohepatic dysplasia in a 4-year-old girl
- 1992
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Ingår i: Medical and Pediatric Oncology. - : Wiley. - 1096-911X .- 0098-1532. ; 20:1, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocellular carcinoma and obliterated hepatic bile duct were found at postmortem examination in a 4-year-old girl with arteriohepatic dysplasia (Alagille's syndrome). AFP level was extremely high. Liver cirrhosis was present on percutaneous needle biopsy 9 months before she succumbed in progressive liver failure. Episodes of repeated gastrointestinal, life-threatening hemorrhages occurred during the last 6 months of her life. Histopathologic findings of the eyes were documented at autopsy.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Békássy, Albert, et al.
(författare)
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Pharmacokinetics of cytosine arabinoside in cerebrospinal fluid and of its metabolite in leukemic cells
- 1990
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Ingår i: Medical and Pediatric Oncology. - : Wiley. - 1096-911X .- 0098-1532. ; 18:2, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- Concentrations of ara-CTP in leukemic cells isolated from CSF and of ara-C in lumbar CSF were measured following intraventricular ara-C administration in two girls with refractory meningeal leukemia. CSF samples were collected with a permanent intrathecal-lumbar catheter. In contrast to the comparatively short retention of ara-C in the CSF (t1/2 1.8 to 2.9 hours), there was a high accumulation and an extremely long retention of ara-CTP in the leukemic cells (t1/2 8.1 to 36 hours). The patients included in this study had an ara-C-resistant disease. No obvious relationship was seen between concentrations of ara-C in the CSF and of ara-CTP in the leukemic cells. Similar studies were performed after simultaneous intraventricular administration of hydrocortison and ara-C. Hydrocortison did not increase ara-CTP retention in the leukemic cells, nor did it effect CSF pleocytosis.
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| 16. |
- Billstrom, R., et al.
(författare)
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Acute myeloid leukemia with inv(16)(p13q22) : Involvement of cervical lymph nodes and tonsils is common and may be a negative prognostic sign
- 2002
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 71:1, s. 15-19
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) with inv(16)(p13q22) or the variant t(16,16)(p13,q22), is strongly associated with the FAB subtype M4Eo. A high incidence of CNS involvement was reported in the 1980s, but otherwise little is known about the pattern of extamedullary leukemia (EML) manifestations in this AML type. We have compiled clinical and cytogenetic data on 27 consecutive AML cases with inv(16)/t(16,16) from southern Sweden. In general, these AMLs displayed the clinical features that have previously been described as characteristic for this disease entity: low median age, hyperleukocytosis, M4Eo morphology, and a favorable prognosis. However, CNS leukemia was only seen in relapse in one patient diagnosed in 1980, whereas the most common EML manifestation in our series was lymphadenopathy (5/27, 19%), most often cervical with or without gross tonsillar enlargement. A review of previously published, clinically informative cases corroborates that lymphadenopathy, with preference for the cervical region, is the most common EML at diagnosis in inv(16)-positive AML (58/175, 33%). CNS leukemia, on the other hand, has been reported in only 17% of the cases, mostly in the relapse setting, with a diminishing frequency over time, possibly due to protective effects of high-dose cytarabine. Other reported EML sites include the scalp, ovaries, and the intestine. Cervicotonsillar EML was in our series associated with a shorter duration of first remission, (P< 0.05), and may hence prove to be an important clinical parameter when deciding treatment strategies in AML with inv(16)/t(16,16). © 2002 Wiley-Liss, Inc.
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| 17. |
- Castor, Anders, et al.
(författare)
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Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia
- 2005
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 11:6, s. 630-637
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Tidskriftsartikel (refereegranskat)abstract
- The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors. Major breakpoint BCR-ABL1 fusions (encoding P210 BCR-ABL1) originated in hematopoietic stem cells (HSCs), whereas minor BCR-ABL1 fusions (encoding P190 BCR-ABL1) had a B-cell progenitor origin, suggesting that P190 and P210 BCR-ABL1 ALLs represent largely distinct tumor biological and clinical entities. The transformed leukemia-initiating stem cells in both P190 and P210 BCR-ABL1 ALLs had, as in ETV6-RUNX1 ALLs, a committed B progenitor phenotype. In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1 ALLs was found to be unaffected by the expansive leukemic stem cell population.
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| 18. |
- Cohen, A, et al.
(författare)
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Endocrinological late complications after hematopoietic SCT in children
- 2008
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 41, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- The main challenge for a pediatric hemato-oncologist today is to obtain a cure for the sick child with the minimum of treatment-related complications. Children on their way to achieving adulthood face many risks after hematopoietic SCT (HSCT). Continuous follow-up includes assessment of organ function, focus on vaccinations and screening for secondary malignancies. Updated treatment protocols are already adjusted according to the knowledge obtained on late effects, and the potential risks for complications are well balanced with expected benefits hopefully resulting in decreased potential risk for organ damage but still maintaining an unchanged or improved survival rate. Recent developments on pre-HSCT regimens, such as the introduction of new anticancer regimens and immunosuppressive agents will hopefully contribute to minimize the frequency and the severity of late complications. Knowledge about increased risk for long-term complications due to cancer therapy and pre-HSCT preparative regimens should encourage each caring physician to stick to follow-up protocols and treatment guidelines not only to improve the survival rate of transplanted children but also to improve their quality of life. To achieve adulthood by maintaining cognitive ability and psychosocial skills is the highest goal for an individual to become a competent member of a society. This review of late endocrine complications after HSCT focuses on growth, pubertal development, thyroid disorders and glucose metabolism in long-term survivors.
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| 19. |
- Dohlsten, M, et al.
(författare)
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Lymphocyte subpopulations and lymphokine production in children with constitutional aplastic anemia
- 1988
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Ingår i: Pediatric Hematology & Oncology. - : Informa UK Limited. - 1521-0669 .- 0888-0018. ; 5:2, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- The expression of lymphocyte surface markers as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN) by mitogen-stimulated peripheral blood mononuclear cells (MNC) have been studied in five children with constitutional aplastic anemia. A significantly reduced T4/T8 ratio was found and two of five patients also had a reduced percentage of B cells. One patient had a high percentage of HLA-DR positive T8+ cells, very suggestive of a high degree of circulating activated T suppressor/cytotoxic cells. IL-2 production was reduced in two patients, whereas IFN production was only reduced in one of these. The abnormalities found correlate with the duration of the bone marrow failure. The patients with the longest duration of bone marrow failure also exhibited the lowest T4/T8 ratio. No spontaneous IFN production was detected in any of the patients. There was no clinical benefit or reversal of the immune abnormalities during and following treatment with cimetidine and cyclosporine A in two patients.
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| 20. |
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| 21. |
- Donnér, M, et al.
(författare)
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Platelet surface-bound IgG and platelet-specific IgG in plasma in childhood thrombocytopenia
- 1990
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Ingår i: Acta Paediatrica Scandinavica. - : Wiley. - 0001-656X .- 0803-5253 .- 1651-2227. ; 79:3, s. 328-334
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Tidskriftsartikel (refereegranskat)abstract
- Quantification of platelet-bound immunoglobulin is widely used in the evaluation of thrombocytopenia. Several methods have been devised among which labelled ligand-binding assays seem to be most appropriate. In series of adult patients such assays have been shown to be superior in separating immune-thrombocytopenia from thrombocytopenia of non-immune causes. We studied 62 children with thrombocytopenia of various causes, using radiolabelled protein A as a ligand to measure platelet-surface bound IgG. The test was highly sensitive (93%) in detecting immune-thrombocytopenia. The specificity, however, was only 57%, which is less than in published studies of adults. In a number of cases presumed to be non-immune-thrombocytopenia, notably a few patients with leukaemia and bone marrow aplasia, we found increased amounts of platelet surface-bound IgG. The significance of this finding is not clear. An indirect assay measuring platelet-specific IgG in plasma was less sensitive (46%) but highly specific for immune-thrombocytopenia (89%). The measurements of platelet-surface-bound IgG and platelet-specific IgG in plasma are of limited diagnostic value in childhood thrombocytopenia but are useful in following the treatment in chronic ITP.
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| 22. |
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| 23. |
- Dykes, Josefina, et al.
(författare)
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Rapid and effective CD3 T-cell depletion with a magnetic cell sorting program to produce peripheral blood progenitor cell products for haploidentical transplantation in children and adults.
- 2007
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Ingår i: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 47:11, s. 2134-2142
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Effective T-cell depletion is a prerequisite for haploidentical peripheral blood progenitor cell (PBPC) transplantation. This study was performed to investigate the performance of magnetic cell sorting–based direct large-scale T-cell depletion, which is an attractive alternative to standard PBPC enrichment procedures. STUDY DESIGN AND METHODS: PBPCs were harvested from 11 human leukocyte antigen (HLA)-haploidentical donors. T cells labeled with anti-CD3–coated beads were depleted with a commercially available magnetic separation unit (CliniMACS, Miltenyi Biotec) with either the Depletion 2.1 (D2.1, n = 11) or the novel Depletion 3.1 (D3.1, n = 12) program. If indicated, additional CD34+ selections were performed (n = 6). Eleven patients received T-cell-depleted grafts after reduced-intensity conditioning. RESULTS: The median log T-cell depletion was better with the D2.1 compared to the D3.1 (log 3.6 vs. log 2.3, p < 0.05) and was further improved by introducing an immunoglobulin G (IgG)-blocking step (log 4.5 and log 3.4, respectively). The D3.1 was superior to the D2.1 (p < 0.05) in median recovery of CD34+ cells (90% vs. 78%) and in median recovery of CD3– cells (87% vs. 76%). The median processing times per 1010 total cells were 0.90 hours (D2.1) and 0.35 hours (D3.1). The transplanted grafts (directly T-cell–depleted products with or without positively selected CD34+ cells) contained a median of 10.5 × 106 per kg CD34+, 0.93 × 105 per kg CD3+, and 11.6 × 106 per kg CD56+. Rapid engraftment was achieved in 10 patients. The incidences of acute graft-versus-host disease were less than 10 percent (Grade I/II) and 0 percent (Grade III/IV). CONCLUSION: The novel D3.1 program with IgG blocking enables highly effective, time-saving large-scale T-cell depletion. Combining direct depletion techniques with standard CD34+ selection enables the composition of grafts optimized to the specific requirements of the patients.
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| 24. |
- Faraci, M, et al.
(författare)
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Non-endocrine late complications in children after allogeneic haematopoietic SCT
- 2008
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 41, s. 49-57
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Tidskriftsartikel (refereegranskat)abstract
- Non-endocrine events represent a heterogeneous group of complications occurring in children who survive long term after haematopoietic SCT. This review highlights the late sequel in a growing child. The preparative regimen itself with high-dose chemotherapy and/or radiotherapy (TBI) or the treatment given before the transplant procedure may cause organ damage with permanent sequel. Immune reconstitution and chronic GvHD have crucial role in occurrence of clinical abnormalities and late severe infections. Autoimmune syndromes may occur after use of novel transplant modalities (cord blood transplantation, reduced intensity conditioning regimen and haploidentical T-cell-depleted SCTs). Exposure to chemo- and/or radiotherapy increases the risk of second malignant neoplasms. Surveillance strategy focusing on each potential complication risk at continuous follow-up will allow vigilant post transplant care. Each paediatrician must be well versed in appropriate monitoring of these complications. Guidelines and recommendations are provided for serious problems occurring at follow-up, which must rapidly be identified so that appropriate intervention can be initiated. To achieve cure at a lowest possible price in terms of suffering and cost expenditures for health care is an extended frontier of paediatric haematopoietic SCT and biggest challenge for a paediatrician.
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| 25. |
- Ghosh, Fredrik, et al.
(författare)
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Intravitreal sustained-release ganciclovir implants for severe bilateral cytomegalovirus retinitis after stem cell transplantation.
- 2002
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 80:1, s. 101-104
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the treatment of cytomegalovirus (CMV) retinitis with intravitreal sustain-release ganciclovir devices in a 16-year-old patient in third remission of acute lymphoblastic leukemia after stem cell transplantation. METHODS: The patient received a stem cell transplant from an unrelated bone marrow donor after which he contracted a serious CMV infection manifested in the lungs and retinae. His immune system at this time was almost completely depleted. Implantation of a sustained-release ganciclovir device was performed in both eyes when retinitis progressed in spite of aggressive antiviral intravenous treatment. RESULTS: No per- or postoperative complications were noted. Infiltrates, hemorrhages and macular edema present preoperatively dissolved over a period of six months. The final visual acuity was 1.0 in both eyes. The patients immune system and lung function slowly recovered during the same time period. CONCLUSIONS: The intravitreal ganciclovir implant provides safe and effective therapy against CMV retinitis, and should be considered in patients acquiring the infection after stem cell transplantation.
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| 26. |
- Heim, Sverre, et al.
(författare)
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A new specific chromosomal rearrangement, t(8;16) (p11;p13), in acute monocytic leukaemia
- 1987
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Ingår i: British Journal of Haematology. - 0007-1048. ; 66:3, s. 323-326
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Tidskriftsartikel (refereegranskat)abstract
- The translocation t(8;16) (p11;p13) was found as the sole deviation from the normal karyotype in three patients with acute monocytic leukaemia. The bone marrow morphology was strikingly similar in the two cases where smears were available for re-evaluation: the leukaemic cells showed signs of differentiation, and active erythrophagocytosis was a particularly conspicuous feature. We suggest that t(8;16) (p11;p13) represents a new consistent abnormality in acute monocytic leukaemia, specifically associated with the differentiated subtype (M5b) and with pronounced phagocytic activity by the leukaemic monocytes.
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| 27. |
- Heim, Sverre, et al.
(författare)
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Bone marrow karyotypes in 94 children with acute leukemia
- 1990
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Ingår i: European Journal of Haematology. - 1600-0609. ; 44:4, s. 227-233
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Tidskriftsartikel (refereegranskat)abstract
- During the last 10 years, we have cytogenetically analyzed at diagnosis bone marrow cells from a total of 94 children with acute leukemia. Of the 78 children with acute lymphatic leukemia (ALL), 53 (68%) had clonal acquired chromosome abnormalities; in the group with acute nonlymphatic leukemia (ANLL), the corresponding proportion was 13 out of 16 (81%). Among the cytogenetically abnormal ALL patients, the most numerous subset was the hyperdiploid cases with stemlines containing 51 or more chromosomes (26 of 53 abnormal cases; 49%). This is a clearly higher proportion than has been reported in large series from other centers. Deletions of 6q were present in 8 cases and rearrangements of 12p in 5. Of the 7 T-cell ALLs, 3 had translocations of the distal part of 7q, i.e., of the region where the beta T-cell receptor is encoded. Only 2 of 26 (8%) patients with leukemic stemlines with more than 50 chromosomes have relapsed; the remainder are still in first remission (mean observation time 42 months). This may be contrasted with 6 of 25 (24%) relapses among the cytogenetically normal (observation time 41 months), and 8 of 27 (30%) relapses among ALL patients with aberrations but with less than 51 chromosomes (observation time 26 months). Our results support the conclusion that the finding of a markedly hyperdiploid leukemia karyotype is indicative of good prognosis in ALL.
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| 28. |
- Heim, Sverre, et al.
(författare)
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High resolution banding analysis of the reciprocal translocation t(6;9) in acute nonlymphocytic leukemia
- 1986
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Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 22:3, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- The cytogenetic, hematologic, and clinical characteristics of a 13-year-old girl with acquired t(6;9)(p23;q34) and dysmyelopoietic syndrome developing into acute myelomonocytic leukemia are described, bringing the total number of patients with t(6;9) and hematologic disease described in the literature up to 19. The diagnosis has been acute myeloid leukemia in the great majority of these patients; only four have had acute myelomonocytic leukemia. High resolution analysis at the 550 band stage localized the breakpoints in chromosomes #6 and #9 to p23 and 9q34.3, respectively. Previous investigations employing high resolution cytogenetics have mapped the typical 9q breakage site in chronic myeloid leukemia to 9q34.1. In situ hybridization studies have demonstrated that the cellular oncogene c-abl remains on the derivative 9q+ chromosome in t(6;9), whereas it is moved to the Ph marker in t(9;22). Thus, the combined data indicate that c-abl is located between 9q34.1 and 9q34.3, i.e., in subband 9q34.2 or its immediate vicinity.
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| 29. |
- Heim, Sverre, et al.
(författare)
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New structural chromosomal rearrangements in congenital leukemia
- 1987
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Ingår i: Leukemia. - 1476-5551. ; 1:1, s. 16-23
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Tidskriftsartikel (refereegranskat)abstract
- The karyotypic abnormalities and clinical data on three patients in whom acute leukemia was diagnosed within the first 6 months of life are presented. The four structural chromosomal rearrangements detected in the bone marrow from these patients, i.e., t(7;12)(q36;p13) and t(1;19)(q11;q11) in case 1, t(2;10;11;12)(q21q31;p13;q13;q24) in case 2, and t(11;19)(q23;p13) in case 3, have not previously been associated with congenital leukemia. Acquired chromosomal changes have until now been reported in only 31 leukemic infants in this age group. Of the total material, 18 patients had acute lymphoblastic leukemia and 16 had acute nonlymphocytic leukemia. The by far most frequently recorded cytogenetic aberration has been t(4q;11q), seen in 14 cases of lymphoblastic leukemia. Although t(4q;11q) has not been found in a single patient with acute nonlymphocytic leukemia, these leukemias have often had other rearrangements involving the same region of 11q. Hence, genetic material around 4q21 may be active in lymphocytic differentiation, whereas gene(s) in 11q23 may be important in the neoplastic process in a less cell-type specific manner and perhaps particularly vulnerable to neoplastic rearrangement in fetal life. The finding of four cases out of 34 with translocations between 11q23 and chromosome 19 indicates that this rearrangement might characterize a specific cytogenetic subgroup of leukemia in the very young.
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| 30. |
- Heim, Sverre, et al.
(författare)
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Reciprocal translocation (11;19)(q23;p13) in congenital acute lymphoblastic leukemia
- 1986
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Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 23:3, s. 239-244
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Tidskriftsartikel (refereegranskat)abstract
- The cytogenetic, clinical, and immunologic findings ina 4-month-old girl with acute lymphoblastic leukemia (ALL) are reported. The malignant lymphoblasts were characterized cytogenetically by the reciprocal translocation t(11;19)(q23;p13); immunologically by an immature pre-B-ALL phenotype. In spite of the high-risk nature of the leukemia, the patient attained complete remission relatively quickly and is still free of disease 3 years after diagnosis. Because the only two previously reported ALL patients with t(11;19) also seem to have responded well to therapy, this cytogenetic abnormality might turn out to be an indicator of favorable prognosis in ALL.
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| 31. |
- Ivancev, Krassi, et al.
(författare)
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Computed tomography in the diagnosis and treatment of mediastinal abnormalities in children
- 1988
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Ingår i: Acta Radiologica. - 1600-0455. ; 29:1, s. 115-120
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-one children with mediastinal abnormalities--14 malignant lymphomas, 4 other primary malignancies, one metastatic and 12 benign lesions--were examined one or several times using CT, which proved to be effective especially for cysts (5 patients), ductus arteriosus aneurysm (2 patients), and intrathoracic liver (one patient). It also supplied important diagnostic information regarding the extent of disease in malignant thymoma (one patient), in neurinoma (one patient), and in Hodgkin's lymphoma (5 patients). It was found to be useful in the monitoring of treatment of patients with lymphomas, in which a small residue, probably a fibrotic remnant, was invariably seen after completion of chemotherapy and irradiation. It was concluded that when the residue was enlarged, the possibility of relapse and even thymic hyperplasia should be considered. However, if CT was performed under general anaesthesia pseudo-widening of the anterior mediastinum could simulate recurrence. Surgical biopsy was found to be necessary in these cases because fine-needle aspiration biopsy was unsuccessful.
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| 32. |
- Jester, S., et al.
(författare)
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Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome
- 2013
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 8:134
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive progressive multiorgan disorder due to mutation in the gene encoding the enzyme Arylsulfatase B (ARSB). Dysfunctional ARSB causes lysosomal accumulation of glycosaminoglycans (GAG). Currently, enzyme replacement therapy (ERT) is preferred to hematopoietic stem cell transplantation (SCT) due to the treatment-related risks of the latter. However, ERT constitutes an expensive life-long treatment. Increased experience and safety of SCT-procedures in recent years suggest that SCT should be further explored as a treatment option. This is the first report on haploidentical SCT in patients with MPS VI. The primary objective was to assess the treatment safety and clinical and biochemical outcome. Patients and methods: Two siblings diagnosed with MPS VI at 10 months of age and at birth with genotype p. C192R, reported as mild to intermediate phenotype, underwent unrelated umbilical cord blood transplantation pre-symptomatic. Due to graft failure, both patients were urgently re-transplantated with haploidentical SCT with the father as donor. Continuous clinical and biochemical status was monitored and concluded 3.8 and 4.6 years after the haploidentical SCT. Results: Haploidentical SCT resulted in prompt and sustained engraftment. Complete donor chimerism was achieved in both patients, apart from mixed B cells chimerism in patient 2. ARSB activity in leukocytes post transplant increased from 0.0 to 19.0 mu kat/kg protein (patient 1) and from 3.6 to 17.9 mu kat/kg protein (patient 2) (ref. 17-40). Total urinary GAG normalized in both patients, although patient 2's values slightly exceed normal range since 6 months. However, dermatan sulfaturia was substantially normalized since 16 months and 12 months post-SCT, respectively. Height was -1.85 SD and -1.27 SD at follow-up. Patient 1 had impaired visual acuity and discrete hepatomegaly. Patient 2 had elevated intraocular pressure and X-ray revealed steep acetabular angles and slightly flattened lumbar vertebrae. Conclusion: This study demonstrates that young children with MPS VI tolerate haploidentical SCT. Normalization of enzyme production and dermatan sulfaturia indicates correction of the inborn error of metabolism and coincide with no obvious symptoms of progressive MPS VI up to 4.6 years post-SCT.
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| 33. |
- Johansson, Bertil, et al.
(författare)
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Granulocytic sarcomas in body cavities in childhood acute myeloid leukemias with 11q23/MLL rearrangements
- 2000
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Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 27:2, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- Three childhood acute monoblastic leukemias (AML M5) with granulocytic sarcomas (GSs) are described. All displayed 11q23/MLL abnormalities, t(9;11)(p22;q23) in two cases and t(11;17)(q23;q21) in one case, constituting around 20% of all 11q23-positive AML cytogenetically investigated in our department. Two of the patients had GS in multiple locations, and all three had abdominal GS. In two of them, t(9;11)-positive GS was diagnosed prior to the diagnosis of AML. Fourteen (1.9%) of 752 published AML cases with 11q23 aberrations have had GS, either as a presenting feature or during disease progression. The incidence of GS has varied significantly (P < 0.05) between children (3.8%) and adults (0.8%). The most common AML subtype has been AML M5 ( approximately 75%) and the most frequent GS sites have been the skin, abdomen, orbit, and thorax. Considering the possibility of underreporting of GS in published cases and the relatively high frequency in our own series, we believe that 11q23/MLL rearrangements may predispose to GS development. Although extramedullary infiltrates in the skin are known to be frequent in cases of AML M5, which is often associated with 11q23 aberrations, the present findings indicate that GS in the abdomen, orbit, and thorax may also be common, especially in pediatric AML. Thus, the possibility of 11q23/MLL-positive GS should be suspected when tumors of uncertain derivation occur in these sites. Finally, the identification of 11q23/MLL abnormalities in GSs in two patients without overt AML underscores the importance of using cytogenetic and molecular genetic investigations as a diagnostic approach in the evaluation of tumorous lesions of unknown origin.
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| 34. |
- Kazanowska, Bernarda, et al.
(författare)
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Pax3-fkhr and pax7-fkhr fusion genes impact outcome of alveolar rhabdomyosarcoma in children
- 2007
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Ingår i: Fetal and Pediatric Pathology. - : Informa UK Limited. - 1551-3823 .- 1551-3815. ; 26:1, s. 17-31
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Tidskriftsartikel (refereegranskat)abstract
- Rhabdomyosarcoma is a highly malignant embryonic tumor of childhood. Two specific translocations t(2;13)(q35;q14) and t(1;13)(p36;q14) have been identified in about 75-80% of ARMS cells. The aim of this multicenter study was to analyze the relationships between the identified fusion transcripts and survival including some selected clinical parameters. The extent of disease was graded according to clinical staging system with following distribution: 3 children with stage I, 4 with stage II, 23 with stage III, and 18 with stage IV spread disease having distant metastases. PAX3-FKHR fusion genes were detected in 28 and PAX7-FKHR fusion genes in 7 tumor biopsy specimens. Children with PAX3-FKHR fusion gene had often distant metastases at presentation (p = 0.03). PAX3-FKHR positive patients with locoregional disease had significantly poorer outcome compared with the ones with PAX7-FKHR positive tumors (p = 0.04). Although analyzed groups were small, significant differences in survival and clinical characteristics between PAX3-FKHR and PAX7-FKHR positive tumors were stated indicating their role in carcinogenesis. In addition, fusion gene analysis is a helpful tool in differential diagnosis of poorly differentiated soft tissue tumors.
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| 35. |
- Korthof, E. T., et al.
(författare)
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Management of acquired aplastic anemia in children
- 2013
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 48:2, s. 191-195
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Forskningsöversikt (refereegranskat)abstract
- The diagnosis of aplastic anemia in children requires exclusion of a variety of inherited or acquired BM failure syndromes with similar phenotypes. An efficient diagnostic plan is important because time from diagnosis to 'final' treatment is directly related to outcome regardless of the therapeutic option chosen. The gold standard of therapy remains hematopoietic SCT with a graft of BM cells for those children with matched sibling donors. Conversely for children without a sibling donor the high response and markedly improved overall survival rates of combined immunosuppressive therapy have proven robust, especially when horse derived anti-thymocyte globuline plus ciclosporine A are used. Incomplete response, relapse and progression to myelodysplasia/leukemia however have emerged as significant long-term issues. Improvements in outcome of alternative donor transplantation and the use of established and novel immunosuppressive agents provide multiple alternatives for treating refractory or relapsed patients. Regardless of the type of therapeutic approach, patients require centralized treatment in a center of excellence, ongoing monitoring for recurrence of disease and/or therapy-related immediate side effects and long-ternn effects. Bone Marrow Transplantation (2013) 48, 191-195; doi:10.1038/bmt.2012.235; published online 7 January 2013
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| 36. |
- Ljungman, P., et al.
(författare)
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Long-term follow-up of HCV-infected hematopoietic SCT patients and effects of antiviral therapy
- 2012
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 47:9, s. 1217-1221
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Tidskriftsartikel (refereegranskat)abstract
- This prospective study was initiated in 1993 with the aim to study late effects and responses to antiviral therapy in a cohort of hepatitis C virus (HCV)-infected patients. A total of 195 patients were included from 12 centers. In all, 134 patients had undergone allogeneic and 61 autologous hematopoietic SCT (HSCT). The median follow-up from HSCT is currently 16.8 years and the maximum 27.2 years. Overall 33 of 195 patients have died of which 6 died from liver complications. The survival probability was 81.6% and the cumulative incidence for death in liver complications was 6.1% at 20 years after HSCT. The cumulative incidence of severe liver complications (death from liver failure, cirrhosis and liver transplantation) was 11.7% at 20 years after HSCT. In all, 85 patients have been treated with IFN; 42 in combination with ribavirin. The sustained response rate was 40%. The rates of severe side effects were comparable to other patient populations and no patient developed significant exacerbations of GVHD. Patients receiving antiviral therapy had a trend toward a decreased risk of severe liver complications (odds ratio=0.33; P=0.058). HCV infection is associated with morbidity and mortality in long-term survivors after HSCT. Antiviral therapy can be given safely and might reduce the risk for severe complications.
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| 37. |
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| 38. |
- Locasciulli, Anna, et al.
(författare)
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Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT)
- 2007
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 92:1, s. 11-18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: The treatment of acquired aplastic anemia (AA) is based on allogeneic bone marrow transplantation (BMT) and immunosuppressive therapy. The aim of this study was to assess the outcome of children and adults with AA treated in the last decade, and to determine whether results have improved in two sequential time periods,1991-1996 and 1997-2002. DESIGN AND METHODS: Two-thousands and seventy-nine consecutive patients with AA, classified according to first-line treatment: BMT (n=1567) or immunosuppressive therapy (n= 912), the patients for the two sequential time periods were studied. Analyses included variables related to patients, disease and transplant. RESULTS: The actuarial 10-year survival was 73% and 68% for BMT or immunosuppressive treatment, respectively (p=0.002). BMT outcome improved significantly with time (69% and 77%, p=001) for both matched sibling donor (MSD) (74% and 80%; p=0.003 ), alternative donor (38% and 65% p=0.0001), and was better in children (79% versus 68%, p<0.0001). Multivariate analysis: favorable predictors (p<0.001) were younger age, transplant beyond 1996, MSD, a short interval diagnosis-transplant , no irradiation. IS: no significant improvement over time (69% and 73% p=0.29). Survival was significantly better in children (81% versus 70%, p=0.001), especially in vSAA(83% versus 62%, p=0.0002). Combined IS was superior to single drug treatment (77% versus 62%, p=0.002). Multivariate analysis: significant predictors of survival: age > or =16 years (p=0.0009), longer interval between diagnosis -treatment (p=0.04), single drug versus combined IS (p=0.02). INTERPRETATION AND CONCLUSIONS: Outcome has improved in subsets of AA patients: those receiving first- line BMT and children with vSAA treated with IS. Age remains a major predictor for both treatments. Early intervention is associated with a significantly better outcome and is strongly recommended, whatever the first-line therapy.
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| 39. |
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| 40. |
- Millot, F, et al.
(författare)
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Imatinib mesylate is effective in children with chronic myelogenous leukemia in late chronic and advanced phase and in relapse after stem cell transplantation
- 2006
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 20:2, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- A multicentric phase 2 study was conducted to determine the efficiency and the tolerance of imatinib mesylate in children with chronic myelogenous leukemia (CML) in advanced phase of the disease, in relapse after stem cell transplantation, or in case of failure to an interferon a-based regimen. In all, 30 children from eight European countries were enrolled. In 18 children assessable for hematologic response, imatinib mesylate induced complete hematologic response in eight (80%) of the 10 patients included in chronic phase and in six (75%) of eight enrolled in advanced phase of the disease with acceptable toxicity. In 27 patients assessable for cytogenetic response, imatinib mesylate induced disappearance of Philadelphia chromosome-positive bone marrow cells in 12 (60%) of 20 children included in chronic phase and in two (29%) of seven included in advanced phase. A reduction of the bcr-abl/abl ratio to less than 10(-4) was achieved in 11 (50%) of the children included in chronic phase. Estimated 12-month overall survival rate was 95% ( 95% CI, 87-100%) for the patients included in chronic phase and 75% ( 95% CI, 45-100%) for those enrolled in advanced phase. Imatinib mesylate is well tolerated and molecular remission can be achieved in children with CML.
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| 41. |
- Paulsson, Kajsa, et al.
(författare)
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A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42
- 2006
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 20:2, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- Although many of the chromosomal abnormalities in hematologic malignancies are identifiable cytogenetically, some are only detectable using molecular methods. We describe a novel cryptic t(7;21)(p22;q22) in acute myeloid leukemia (AML). FISH, 3'RACE, and RT-PCR revealed a fusion involving RUNX1 and the ubiquitin-specific protease (USP) gene USP42. The genomic breakpoint was in intron 7 of RUNX1 and intron 1 of USP42. The reciprocal chimera was not detected - neither on the transcriptional nor on the genomic level - and FISH showed that the 50 part of USP42 was deleted. USP42 maps to a 7p22 region characterized by segmental duplications. Notably, 17 kb duplicons are present 1Mb proximal to USP42 and 3Mb proximal to RUNX1; these may be important in the genesis of t(7; 21). This is the second cryptic RUNX1 translocation in hematologic malignancies and the first in AML. The USPs have not previously been reported to be rearranged in leukemias. The cellular context in which USP42 is active is unknown, but we here show that it is expressed in normal bone marrow, in primary AMLs, and in cancer cell lines. Its involvement in the t(7; 21) suggests that deregulation of ubiquitin-associated pathways may be pathogenetically important in AML.
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| 42. |
- Perez de Sá, Valéria, et al.
(författare)
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Hemodilution during bone marrow harvesting in children
- 1991
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Ingår i: Anesthesia and Analgesia. - 1526-7598. ; 72:5, s. 645-650
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Tidskriftsartikel (refereegranskat)abstract
- Eight children (1--17 yr) underwent bone marrow harvesting while in cytostatic-induced remission of their disease (leukemia [n = 6], Ewing sarcoma, and non-Hodgkin lymphoma). After the induction of general anesthesia, all patients were loaded with 10 mL/kg of a 6% high-molecular dextran solution (Macrodex — Pharmacia), which resulted in a significant preoperative decrease in hematocrit (Hct) from 32% ± 6% to 28% ± 5% (hypervolemic hemodilution) and also allowed the procedure to be performed without systemic heparinization. The blood aspirated during the harvest (24 ± 6 mL/kg; mean ± SD) was replaced with a solution of 6% dextran and Ringer's acetate solution, and the Hct decreased from 28% ± 5% to a minimum of 18% ± 3%. Immediately after the harvest, 10 mL/kg of homologous packed red blood cells was transfused, increasing Hct to 25% ± 3%. Oxygen saturation in the superior caval vein (Scvo2) decreased from 79% ± 4% before the harvest to 70% ± 3% (P < 0.01) at the end of it, and then increased to 74% ± 3% after the transfusion of homologous packed red blood cells. There was a strong linear correlation between mean values for Hct and Scvo2 during the various stages (r = 0.99). Mean heart rate decreased gradually during the procedure, from 106 ± 10 to 86 ± 7 beatslmin. There was no significant change in arterial pressure, but cardiac output measured by impedance cardiography was about 30% greater during harvesting than during undisturbed anesthesia. Pulse oximetric saturation was 99% or 100% throughout. Caval venous blood lactate and pyruvate concentrations remained within normal limits in all children. Recovery after anesthesia was uneventful, except in one child in whom severe shivering developed. H is concluded that the hemodilution resulted in a statistically but not clinically significant decrease in Scvo2 that was well tolerated by the patients as judged from hemodynamic responses as well as levels of arterial oxygen saturation (Sao2) and blood lactate.
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| 43. |
- Pronk, Cornelis JH, et al.
(författare)
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Aplastisk anemi hos barn botas med immunsuppression.
- 2004
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Ingår i: Läkartidningen. - 0023-7205. ; 101:42, s. 5-9
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Tidskriftsartikel (refereegranskat)abstract
- Acquired aplastic anemia (AA) is considered to be an autoimmune mediated disease whereas in inherited bone marrow failure syndromes the genetic abnormalities account for the bone marrow dysfunction. The only curative treatment for inherited AA is hematopoietic stem cell transplantation (HSCT). Successful treatment for acquired AA has traditionally been considered with HSCT, whereas single agent therapy with different immunosuppressive (IS) drugs has been disappointing as alternative treatment modality when sibling donors were lacking. Over the last decades however, treatment with combined IS (e.g. Cyclosporin-A, CsA, + Anti Thymocyte Globuline, ATG, has made great progress, resulting in hematological reconstitution comparable with results achieved with HSCT. We present a single centre retrospective analysis of 24 children with primary marrow failure at onset and treated subsequently during the years 1981-2002. 16 children were diagnosed with acquired severe aplastic anemia (SAA), 6 Fanconi anemia (FA), 1 Seckel syndrome and 1 with congenital amegakaryocytic thrombocytopenia. International randomized co-operative studies are required in order to gain knowledge on best treatment options of the disease. Long-term follow-up is of vital importance in order to elucidate the risk of secondary clonal diseases (PNH, MDS and leukemia) and other late effects.
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| 44. |
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| 45. |
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| 46. |
- Saarinen-Pihkala, Ulla M, et al.
(författare)
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RALLE Pilot: Response-guided Therapy for Marrow Relapse in Acute Lymphoblastic Leukemia in Children.
- 2012
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Ingår i: Journal of Pediatric Hematology/Oncology. - 1536-3678. ; 34:4, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- Despite improved treatment results of childhood acute lymphoblastic leukemia (ALL), 20% to 30% have a relapse, and then the outcome is very poor. We studied 40 children with ALL marrow relapse piloting an ALL relapse protocol with well-known drugs and drug combinations by using a concept of response-guided design. We also measured response in logarithmic fashion. Our primary end points were achievement of M1 marrow status, minimal residual disease status below 10, and second remission. The remission induction rate was 90% with 10% induction mortality. After the A blocks (dexamethasone, vincristine, idarubicin and pegylated L-asparaginase), 85% had M1 status, 39% had minimal residual disease ≤1×10, and 66% had 2 to 3 log response. After B1 block (cyclo, VP-16) the figures were 92%, 58%, and 83%, respectively. Twenty-five of 40 patients received allogeneic stem cell transplantation. Three-year event-free survival of the whole cohort was 37%, and the relapse rate was 38%. Three-year event-free survival by risk group was 53% for late, 34% for early, and 21% for very early relapses. An ALL marrow relapse nonresponsive to steroids, vincristine, asparaginase, anthracyclines, and alkylating agents is uncommon, and these classic drugs can still be advocated for induction of ALL relapse. The problems lie in creating a consolidation capable of preventing particularly posttransplant relapses.
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| 47. |
- Socie, Gerard, et al.
(författare)
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Granulocyte-stimulating factor and severe aplastic anemia: a survey by the European Group for Blood and Marrow Transplantation (EBMT)
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 109:7, s. 2794-2796
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies suggested a link between the use of G-CSF and increased incidence of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after immunosuppressive therapy (IST) for severe aplastic anemia (SAA). This European survey included 840 patients who received a first-line IST with (43%) or without (57%) G-CSF. The incidences of MDS/AML in patients who did or did not receive G-CSF were 10.9% and 5.8%, respectively. A significantly higher hazard (1.9) of MDS/AML was associated with use of G-CSF. Relapse of aplastic anemia was not associated with a worse outcome in patients who did not receive G-CSIF as first therapy, whereas relapse was associated with a significantly worse outcome in those patients who received G-CSF. These results emphasize the necessity of the current European randomized trial comparing IST with or without G-CSF and to alert physicians that adding G-CSIF to IST is currently not standard treatment for SAA.
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| 48. |
- Soller, Maria Johansson, et al.
(författare)
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Cytogenetic findings in pediatric renal cell carcinoma
- 2007
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Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 173:1, s. 75-80
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Tidskriftsartikel (refereegranskat)abstract
- Adenocarcinomas of the kidney are rare childhood tumors. Only 30 cases with chromosomal abnormalities have been reported, and neither their karyotypic characteristics nor the molecular mechanisms behind their pathogenesis are clear, except for a special group of papillary tumors characterized by X-chromosome abnormalities. We have cytogenetically analyzed short-term cultured cells from two pediatric renal carcinomas, one papillary, and one chromophobe renal cell carcinoma, revealing the following karyotypes: 58-60,XX,-X,-1,+7,-8,-9,-11,-14,-15,+17,-18,-19,-21,-22 and 36,X,-X,-1,-2,-5,-6,-9,-10,-13,-17,-21/37,idem,+r/36,idem,-14,+1-2r, respectively. The findings indicate that subsets of pediatric renal cell carcinoma show karyotypes that are similar to their adult counterparts.
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| 49. |
- Stegmaier, S, et al.
(författare)
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Identification of various exon combinations of the ews/fli1 translocation: An optimized RT-PCR method for paraffin embedded tissue a report by the CWS-Study group - A report by the CWS-study group
- 2004
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Ingår i: Klinische Pädiatrie. - : Georg Thieme Verlag KG. - 1439-3824 .- 0300-8630. ; 216:6, s. 315-322
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chromosomal translocations t(11;22) (q24;q12) are characteristic of about 80-90% of Ewing's sarcoma family of tumors [bone and soft tissue Ewing's sarcoma and peripheral neuroectodermal tumors (PNET)]. They generate ews/fli1 rearrangements showing great diversity in breakpoint exon combination. In about 5% of Ewing's tumors, ews is fused to the erg gene at 21q22. The various chimeric proteins encoded may function as aberrant oncogenic transcription factors. These specific translocations can be used for exact molecular diagnosis in these poorly differentiated small round-cell tumors. Moreover, the prognostic relevance of different translocational variants has been previously suggested. Furthermore, the sensitive molecular detection of minimal metastatic and residual disease and its clinical significance can be evaluated. To address these questions more definitively in the large number of patients registered in multicenter studies, it is often necessary to access archival paraffin-embedded tumor tissue if no fresh or frozen tumor material is available for analysis by RT (reverse transcription)-PCR. Specific problems arise from formalin-fixed and paraffin-embedded tissue due to the degradation of RNA and insufficient extraction efficiency. Therefore, primer distance and product size are limited for successful PCR amplification. This conflicts with the requirement for identification of various possible exon combinations by PCR simultaneously using one single primer pair with larger distance. Patients: We examined paraffin embedded soft part tumor tissue samples from 47 Ewing's tumor patients. Patients were treated according to either CWS (Cooperative Weichteilsarkomstudie, CWS-91 or CWS-96) or Euro-E.W.I.N.G. 99 therapy protocols. Method: We established a novel RT-PCR method, using 3 different exon specific sets of PCR primer pairs, selected according to the coding ews and fli1 nucleotide sequences (NCBI database), suitable for RT-PCR identification of variant ews/fli1 fusion transcripts in RNA isolated from formalin-fixed, paraffin-embedded tissue. For use in combination with ews-primer, an erg specific primer was selected to alternatively test for ews/erg fusion transcripts. As positive control for the integrity of isolated mRNA, we used the ubiquitously expressed gapdh transcript for RT-PCR amplification in each sample. Results: In 31 cases (= 66%) of 47 paraffin samples of Ewing's tumors analysed, gapdh control indicated adequate quality of RNA. In 16 cases no gapdh control fragment was amplifiable, nevertheless in 2 of these 16 samples distinct ews fusion products could be detected. In 23 cases we identified ews fusion transcripts. Thereof in 65% ews exon 7 being fused to fli1 exon 6 (fusion type I), in 22% to fli1 exon 5 (fusion type II). In 4% each ews exon 10 being juxtaposed to fli1 either exon 6 or exon 5, respectively. An ews/erg fusion was detected in 4% (ews exon 7 fused to erg exon 6). In 10 samples, a gapdh fragment was amplified, but no ews/fli1 or -erg fusion transcript could be identified. The reference pathological review (I. L., Kiel, Germany) disproved the primary histopathology in 5 cases. Conclusions: Using our different sets of exon specific primer pairs, it was possible to detect 4 different breakpoints of ews/fli1 fusion transcripts and the ews/erg fusion by RT-PCR in RNA isolates from formalin-fixed, paraffin-embedded Ewing's tumor tissue. This method can be a very useful alternative in clinical situations (to ensure diagnosis and perform minimal metastatic and residual disease investigations) and in order to assess prognostic significance of translocation subtype when no fresh tumor tissue is available.
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| 50. |
- Stegmaier, Sabine, et al.
(författare)
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Prognostic Value of PAX-FKHR Fusion Status in Alveolar Rhabdomyosarcoma: A Report From the Cooperative Soft Tissue Sarcoma Study Group (CWS)
- 2011
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 57:3, s. 406-414
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Tidskriftsartikel (refereegranskat)abstract
- Background. Alveolar Rhabdomyosarcomas (RMA) are characterized by chromosomal translocations, fusing the PAX3 or PAX7 gene with FKHR in about 85%. Previous studies have suggested that the fusion type is associated with prognosis. In order to investigate the predictive value of the PAX-FKHR fusion status on disease outcome of patients with RMA treated in the CWS trials we performed a retrospective analysis. Procedure. Between 1986 and 2004, out of 446 patients with RMA treated in four consecutive CWS trials, tumor samples from 126 patients were available for RT-PCR analysis. Survival depending on fusion status in context with known clinical risk-factors was analyzed. Results. Out of 126 samples, 121 had adequate quality for PAX-FKHR fusion status analysis. PAX-FKHR fusions were detected in 101 samples: 60% PAX3-FKHR and 24% PAX7-FKHR fusions, 17% were fusion-negative. There was no significant difference in survival between patients with PAX3-FKHR versus PAX7-FKHR positive tumors. The fusion transcript negative cohort showed a more favorable outcome than the fusion transcript positive cohort among patients with metastatic disease. From the established clinical risk-factors none was associated with a significantly higher risk of failure or death in a multivariate analysis. Conclusions. PAX-FKHR fusion type was not a significant predictor for survival in our analysis. Moreextensive molecular analyses are needed to identify features with prognostic relevance and useful therapeutic impact. Pediatr Blood Cancer 2011; 57: 406-414. (C) 2011 Wiley-Liss, Inc.
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