| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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