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11/62. A graft-versus-tumor effect in a patient with ependymoma who received an allogenic bone marrow transplant for therapy-related leukemia. Case report.

    Graft-versus-leukemia effect is an immune-mediated antitumor phenomenon associated with allogenic bone marrow transplants (BMTs) for hematological malignancies, and recent findings have indicated that a similar effect could occur in some solid tumors such as breast cancers. The authors report on a 42-year-old man with a recurrent ependymoma who received an allogenic BMT for therapy-related leukemia. After transplantation, the patient developed chronic graft-versus-host disease, which was controlled with steroid agents. Interestingly, the recurrent ependymoma regressed steadily over the next 21 months posttransplant, until the tumor became almost undetectable on magnetic resonance images. This case indicates that the graft-versus-tumor effect, mediated by cytotoxic T cells, may be able to target intraparenchymal neuroepithelial tumors, despite the brain's generally recognized status as an immunoprivileged organ.
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12/62. Mature B-cell leukemias with more than 55% prolymphocytes: report of 2 cases with burkitt lymphoma-type chromosomal translocations involving c-myc.

    CONTEXT: The molecular genetic events involved in the pathogenesis of mature B-cell leukemias with more than 55% prolymphocytes are not well characterized. We have encountered 2 such cases in which conventional cytogenetic analysis identified burkitt lymphoma-type chromosomal translocations involving 8q24. OBJECTIVE: To assess these 2 cases for involvement of the c-myc gene using fluorescence in situ hybridization analysis with probes specific for the c-myc and immunoglobulin heavy-chain (IgH) genes. RESULTS: In both cases, conventional cytogenetic analysis demonstrated complex karyotypes, including chromosomal translocations involving 8q24. In case 1, a case of de novo prolymphocytic leukemia, the t(8;14)(q24;q32) was detected. In case 2, a case of chronic lymphocytic leukemia in prolymphocytoid transformation, the t(8;22)(q24;q11) was identified. fluorescence in situ hybridization studies showed c-myc/IgH fusion signals in case 1, proving the presence of the t(8;14). Split c-myc signals without fusion to IgH were observed in case 2, proving c-myc gene rearrangement and consistent with the t(8;22). CONCLUSION: These results suggest that c-myc gene alterations may be involved in the pathogenesis of a subset of mature B-cell leukemias with more than 55% prolymphocytes.
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13/62. Secondary myelodysplastic syndrome and leukemia following 131I-metaiodobenzylguanidine therapy for relapsed neuroblastoma.

    PURPOSE: To describe three patients with secondary leukemia after treatment with 131I-metaiodobenzylguanidine (MIBG) for neuroblastoma. methods: Of 95 children with refractory neuroblastoma treated with 131I-MIBG at UCSF, 3 have been identified with secondary myelodysplasia/leukemia. The case records and bone marrow results were reviewed, along with a review of the literature. RESULTS: Three patients developed secondary myelodysplasia/leukemia, at 7, 11, and 12 months following 131I-MIBG therapy. Cytogenetic abnormalities included -7q/-5, -7/ 2q37, -11 and 12. Three additional cases were found in literature review of 509 reported patients treated with 131I-MIBG for neuroblastoma. CONCLUSIONS: Therapy with 131I-MIBG may contribute to the risk of secondary leukemia in patients who have received intensive chemotherapy, thought the risk of this complication is far lower than the risk of disease progression. Further monitoring for this complication is indicated.
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keywords = leukemia
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14/62. Alteration of the c-fms gene in a blood sample from a Thorotrast individual.

    We analyzed six different tissue dna samples from a leukemic individual who received an injection of Thorotrast for alterations in proto-oncogene or tumor-suppressor gene structure. Our examination of the dna indicated an alteration of the c-fms gene in the blood sample from this individual. This locus showed a deletion in which the 3' end of the deleted region maps between exons 11 and 12. In this particular case, the type of leukemia is unknown but myeloid leukemia is a neoplasm associated with individuals injected with Thorotrast. It is possible that the alteration in the c-fms gene of this individual is a consequence of the radiation exposure. No apparent alterations in the c-mos gene were observed in any of the tissues from the individual. This is in contrast to previous studies that described alterations in methylation patterns associated with the c-mos locus in radium-exposed individuals. A number of the individuals exposed to radium also had alterations of the retinoblastoma gene while no such alterations were observed in any tissue dna samples from this Thorotrast case. It is possible that our inability to detect alterations of the c-mos and retinoblastoma gene may be attributable to the nature of alpha-emitting radionuclides or their distribution, or to the limited set of tissues available for analysis.
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keywords = leukemia
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15/62. Cancer risk following exposure to Thorotrast: overview in relation to a case report.

    Radioactive measurements and histopathologic findings are described in a patient administered Thorotrast, a radiographic contrast agent, 36 y prior to death and compared with cancer risks noted in epidemiologic studies. This person [designated as U.S. uranium Registry (USUR) Case 1001] had prearranged for donation of her body to the USUR and the National Cancer Institute for study. Elevated levels of radioactivity were noted in those organs in which excess cancers have been reported in epidemiologic surveys of Thorotrast-exposed subjects. Hepatic tissue in USUR Case 1001 was estimated to have received an average lifetime absorbed dose of 16.2 Gy, based on radiochemical analyses, consistent with the high risks for liver tumors reported in all studied populations. Thorotrast was present throughout the bone marrow of USUR Case 1001, who died secondary to complications of refractory anemia with excess blasts (RAEB). Elevated risks for acute myeloid leukemia have been noted in Thorotrast patients, and more recently, cases of RAEB and RAEB in transformation have been reported. The thorium decay series includes the bone-seeking radionuclides 224Ra and 228Ra, which have been associated with high risks for osteosarcomas, although the association between Thorotrast and bone cancer is not as convincing. The skeleton of USUR Case 1001, however, contained significant levels of radioactivity. Other tissues evaluated in USUR Case 1001 included lung, eye, kidney, and breast, which did not contain elevated levels of radioactivity.
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keywords = leukemia
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16/62. Chronic myeloid leukemia in a man with papillary carcinoma of the thyroid treated with radioactive iodine.

    leukemia as a second malignancy after treatment of thyroid cancer is rare. Most cases reported in the literature have occurred after cumulative doses higher than 800 mCi and it is most commonly acute leukemias. We report a case of chronic myeloid leukemia (CML) occurring in a 40-year-old man 14 years after treatment of papillary thyroid carcinoma. Our patient had the longest interval between the diagnosis of CML and administration of 131I.
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17/62. Chronic myeloid leukemia after treatment with 131 for thyroid carcinoma.

    A 27-year-old male developed philadelphia chromosome-positive chronic myeloid leukemia (CML) 13 years after a first dose of radioiodine (131I) therapy for papillary thyroid carcinoma. He had received a cumulative 131I dose of 670 mCi, in 8 divided doses over 8 years, up to April 1998, for ablation of 131I avid tissues over the anterior neck region. The leukemogenic potential of radioactive iodine has been pointed out by many authors, but most reported cases have been acute leukemias. A literature review disclosed only 9 cases similar to ours. At present, there is no evidence to prove whether the development of CML after thyroid carcinoma represents a treatment-induced complication, a coincidence, or an increased susceptibility to secondary malignancies due to the malignant process itself.
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18/62. Unbalanced 6p translocation as primary karyotypic anomaly in secondary acute nonlymphocytic leukemia.

    A case of acute nonlymphocytic leukemia after radiochemotherapy for Hodgkin's disease, with a rearrangement of 6p23 region, is described. This chromosome change, which has been previously reported in secondary leukemias or myelodysplastic syndromes, was an isolated karyotypic anomaly in our case, which strongly supports the nonrandom involvement of chromosome 6p in induced leukemias.
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keywords = leukemia
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19/62. Cutaneous nodes in a patient with advanced papillary carcinoma of the thyroid.

    Cutaneous metastasis from thyroid carcinoma is infrequent. leukemia as a second malignancy after treatment of thyroid cancer is also rare. We present a patient with a relapsed thyroid carcinoma treated with thyroid ablation with I 131 and loco-regional radiotherapy, who consulted by global worsening, weight lost, and multiple cutaneous nodes. Our patient is unusual in that she showed multisystem involvement at the time of hospital admission, and the specific skin lesions were the first sign of her acute monocytic leukemia.
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keywords = leukemia
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20/62. Erythroleukemia and gastric cancer following thorotrast injection.

    A 63-year-old male, who had undergone angiography using thorium dioxide (Thorotrast) at the age of 15 for investigation of a giant hemangioma on his left thigh, developed anemia in September 1986 (47 yrs after the angiography). A diagnosis of erythroleukemia was made from a bone marrow study which showed 56.4% megaloblastoid erythroblasts and 12.8% myeloblasts. autopsy revealed Thorotrast deposition in the liver, spleen, bone marrow, and lymph nodes, and monotonous proliferation of myeloblasts in the bone marrow. He also had differentiated tubular adenocarcinoma of the posterior wall of the stomach.
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keywords = leukemia
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