1/35. Acute monoblastic leukemia in a child following chemotherapy for neuroblastoma.The long-term effects of childhood cancer and its therapy are serious problems that deserve attention. One of the most important late effects is the development of secondary malignancy. We encountered a girl with neuroblastoma who developed acute monoblastic leukemia as a secondary malignancy, 32 months after starting treatment for the primary tumor at the age of 4 years and 10 months. For the primary tumor, she had received cyclophosphamide, ifosphamide, etoposide, epirubicin, cisplatin, and vincristine during a period of 20 months; no radiotherapy was given. cytogenetic analysis of the leukemic cells showed no specific changes, but a rearrangement of the mixed lineage leukemia gene (chromosome 11q23 translocation) was subsequently found by reverse transcription polymerase chain reaction. The survival time after onset of the secondary malignancy was brief. The leukemogenic hazards of cancer treatment should be weighed against their therapeutic benefits.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
2/35. Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with dna topoisomerase ii inhibitors.Leukemias with MLL gene translocations are a complication of primary cancer treatment with dna topoisomerase ii inhibitors. How early translocations appear during primary cancer treatment has not been investigated. We tracked the leukemic clone with an MLL gene translocation during neuroblastoma therapy in a child who developed acute myeloid leukemia. The karyotype of the leukemic clone showed del(11)(q23). We used panhandle PCR-based methods to isolate the breakpoint junction involving MLL and an unknown partner gene. Marrow dna from neuroblastoma diagnosis and dna and rna from serial preleukemic marrows were examined for the translocation. The karyotypic del(11)(q23) was a cryptic t(11;17). GAS7, a growth arrest-specific gene at chromosome band 17p13, was the partner gene of MLL. Two different MLL-GAS7 fusion transcripts were expressed. The translocation was already detectable by 1.5 months after the start of neuroblastoma treatment. The translocation was not detectable in the marrow at neuroblastoma diagnosis or in peripheral blood lymphocyte DNAs of six normal subjects. GAS7 is a new partner gene of MLL in treatment-related acute myeloid leukemia. MLL gene translocations can be present early during anticancer treatment at low cumulative doses of dna topoisomerase ii inhibitors. Although MLL has many partner genes and most have not been characterized, panhandle PCR strategies afford new means for detecting MLL gene translocations early during therapy when the partner gene is unknown.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
3/35. Secondary leukemia in a child with neuroblastoma while on oral etoposide: what is the cause?To date little has been reported about the risk of therapy-related leukaemia (t-AML) in children receiving oral etoposide therapy. The authors present a case of t-AML that developed in a child with metastatic neuroblastoma 18 months after he received oral etoposide, given for palliation purpose. The leukemic blasts were examined by morphological, immunohistochemical, cytogenetic, and molecular genetic analyses. Although the t-AML developed following oral etoposide therapy, the child had previously received high-dose, multiagent chemotherapy, and rearrangement of the MLL gene was not demonstrated. The use of modern multiagent therapy often makes it difficult to appropriately apportion blame for causation of specific side effects. Moreover, the etiology of t-AML and mechanism of leukemogenesis are likely to be multifactorial and complex. Further studies on the precise association with different therapies are thus needed. Oral etoposide remains an effective palliative agent and its usage should not be excluded without most careful consideration of the risks.- - - - - - - - - - ranking = 0.66666666666667keywords = leukemia (Clic here for more details about this article) |
4/35. incidence of occult cancer in children presenting with musculoskeletal symptoms: a 10-year survey in a pediatric rheumatology unit.OBJECTIVES: To assess the frequency and types of cancer found in children presenting to our Unit with musculoskeletal symptoms over a 10-year period. methods: The medical records of patients with musculoskeletal symptoms and a final diagnosis of cancer were reviewed. In each case age, gender, presenting symptoms, laboratory data, diagnostic procedures, provisional and final diagnoses, and time between clinical onset and correct diagnosis were reviewed. RESULTS: An underlying neoplasia was found in 10 of 1,254 patients (<1%) complaining of musculoskeletal symptoms. The types of malignancies found included acute lymphocytic leukemia (ALL) (6 cases), lymphoma (2 cases), neuroblastoma (1 case), and Ewing's sarcoma (1 case). The mean time between disease onset and final diagnosis was 3.2 months. The most common presenting feature was monoarthritis, involving the larger joints such as the elbows, knees or ankles. Juvenile idiopathic arthritis (JIA) was the most frequent provisional diagnosis. In the preliminary hematologic evaluation, eight patients had an increased erythrocyte sedimentation rate (ESR) or c-reactive protein (CRP) value. White blood cell (WBC) count was normal in almost all children, with a normal differential count. Lactic dehydrogenase (LDH) was raised in all children. bone marrow aspirates and lymph node or bone biopsies were necessary to reach the final diagnosis. CONCLUSIONS: A malignancy should always be excluded in children with musculoskeletal symptoms, especially when the clinical pattern is not characteristic of a specific rheumatic disease. Routine laboratory tests may be misleading. The simultaneous presence of high LDH or alpha-hydroxybutyric dehydrogenase (alpha-HBDH) levels and raised ESR or CRP, even with normal blood cell counts, should lead to additional investigations. RELEVANCE: All patients presenting with arthritis or other musculoskeletal symptoms should have a thorough clinical examination. Disproportionate pain levels and an atypical pattern of "arthritis," especially in the presence of systemic manifestations, suggest a possible underlying malignancy.- - - - - - - - - - ranking = 0.16666666666667keywords = leukemia (Clic here for more details about this article) |
5/35. t(3;11) translocation in treatment-related acute myeloid leukemia fuses MLL with the GMPS (GUANOSINE 5' MONOPHOSPHATE SYNTHETASE) gene.The partner gene of MLL was identified in a patient with treatment-related acute myeloid leukemia in which the karyotype suggested t(3;11)(q25;q23). Prior therapy included the dna topoisomerase ii inhibitors, teniposide and doxorubicin. Southern blot analysis indicated that the MLL gene was involved in the translocation. cDNA panhandle polymerase chain reaction (PCR) was used, which does not require partner gene-specific primers, to identify the chimeric transcript. Reverse-transcription of first-strand cDNAs with oligonucleotides containing known MLL sequence at the 5' ends and random hexamers at the 3' ends generated templates with an intra-strand loop for PCR. In-frame fusions of either MLL exon 7 or exon 8 with the GMPS (GUANOSINE 5'-MONOPHOSPHATE SYNTHETASE) gene from chromosome band 3q24 were detected. The fusion transcript was alternatively spliced. guanosine monophosphate synthetase is essential for de novo purine synthesis. GMPS is the first partner gene of MLL on chromosome 3q and the first gene of this type in leukemia-associated translocations. (blood. 2000;96:4360-4362)- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
6/35. Simultaneous occurrence of advanced neuroblastoma and acute myeloid leukemia.The authors report the case of a 4-year-old boy with a diagnosis of stage IV neuroblastoma (NB), who had been treated with 6 cycles of cyclophosphamide, doxorubicin, cisplatin, and etoposide for 12 months. The patient reached partial remission and presented a diagnosis of acute myelomonocytic leukemia (M4 AML), confirmed by immunophenotyping. After 2 months of therapy for leukemia, the child died with both malignancies in activity. A necropsy histologically confirmed the simultaneity of the two diseases. The authors review the possibilities of this association. The review leads to the conclusion that AML can occur as a secondary malignancy after the onset of the neuroblastoma, or be suggested by a misdiagnosis. The simultaneous occurrence of both as described here is not, however, found in the literature, to the best of the authors' knowledge.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
7/35. Subsequent cancer in patients with Ewing's sarcoma.Among 31 long-term survivors of Ewing's sarcoma, two patients developed second primary cancers, compared to an expected number of 0.03 (relative risk = 72; 95% confidence limit = 8-259). One patient had renal medullary neuroblastoma, which is not known to be related to Ewing's tumor or its therapy. The second patient had a bone fibrosarcoma, arising at the primary tumor site, which was thought to be radiation-induced. The risk of radiation-induced bone sarcomas was lower, although not significantly so, than in a recently reported series of Ewing's tumor. These two reports suggest that patients with Ewing's sarcoma have a tendency to develop radiogenic sarcomas following primary megavoltage radiation therapy. The lowest radiation dose consistent with local tumor eradication should be employed to minimize the risk of subsequent radiogenic cancer.- - - - - - - - - - ranking = 1.2983894556535keywords = radiation-induced (Clic here for more details about this article) |
8/35. Second malignancies in children with neuroblastoma after combined treatment with 131I-metaiodobenzylguanidine.BACKGROUND: (131)I-metaiodobenzylguanidine ((131)I-MIBG) is selectively taken up by cells of neural crest origin, allowing targeted radiotherapy of tumors such as neuroblastoma (NB) and pheochromocytoma. radiotherapy may provide additional benefits in the treatment of NB, with moderate side effects such as hematologic and thyroid toxicity. However, with longer follow-up, other complications might occur. We describe our experience with second cancers occurring in children treated with (131)I-MIBG and chemotherapy. methods: The clinical records of 119 consecutive NB cases treated with (131)I-MIBG at a single institution between 1984 and 2001 were reviewed for the occurrence of a second malignant neoplasm (SMN). RESULTS: overall, five cases of SMN occurred in the study patients. In particular, two cases of myeloid leukemia, one of angiomatous fibrous histiocytoma, one of malignant schwannoma, and one case of rhabdomyosarcoma were detected. The schwannoma and the rhabdomyosarcoma developed within the residual neuroblastic mass after first-line therapy. CONCLUSIONS: Should (131)I-MIBG treatment become more broadly employed in the therapeutic strategy for neuroblastoma, the risk of second cancer will have to be taken into consideration. The organization of an international registry of subjects treated with (131)I-MIBG might better define the frequency and features of second malignancies following this radiometabolic approach.- - - - - - - - - - ranking = 0.16666666666667keywords = leukemia (Clic here for more details about this article) |
9/35. Acute lymphoblastic leukemia occurring as a second malignant neoplasm in childhood: report of three cases and review of the literature.PURPOSE: The long-term effects of childhood cancer and its therapy are a problem of increasing concern. One of the most important of these late effects is the development of second malignant neoplasms (SMNs), which occur in approximately 8% of children within 20 years of diagnosis of a malignancy. These secondary cancers may result (individually or in combination) from increased genetic susceptibility, the mutagenic effects of chemotherapy and/or radiation therapy, or chance. Whereas the development of acute nonlymphocytic leukemia (ANLL) as an SMN is a well-recognized phenomenon, acute lymphoblastic leukemia (ALL) has been infrequently described as an SMN in either adults or children. patients AND methods: We report three patients treated at our institution in whom ALL developed as an SMN after treatment for neuroblastoma, Wilms' tumor, and Hodgkin's disease. These cases prompted us to review the published literature for cases of secondary ALL in childhood. patients whose initial malignancy was diagnosed at age less than 16 years were classified as pediatric patients. SMNs were defined as cancers of clearly distinct histologic type occurring 6 or more months after diagnosis of the first malignant neoplasm. RESULTS: Including the three index cases, a total of 18 children with secondary ALL are reviewed, and the clinical features are discussed and compared with those of secondary ANLL. CONCLUSIONS: This review summarizes the published case histories of secondary ALL. The data suggest that ALL represents approximately 5% to 10% of the cases of acute leukemia that arise as SMNs in both adults and children.- - - - - - - - - - ranking = 1.1666666666667keywords = leukemia (Clic here for more details about this article) |
10/35. Metastatic neuroblastoma presenting as a mandibular mass.neuroblastoma is the third most common type of cancer seen in children, after leukemia and tumours of the central nervous system. Although bony metastasis to the skull and the orbits has been well described, metastasis to the mandible is exceptional; 32 cases have been reported. Two more are presented here, along with a short review of the topic emphasizing the radiographic features and the differential diagnosis.- - - - - - - - - - ranking = 0.16666666666667keywords = leukemia (Clic here for more details about this article) |
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