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1/431. Iron depletion by phlebotomy with recombinant erythropoietin prior to allogeneic transplantation to prevent liver toxicity.

    iron overload may induce liver toxicity after hematopoietic stem cell transplantation (HSCT), but it is not known if iron depletion prior to HSCT can reduce the risk of severe toxicity in this setting. We used subcutaneous recombinant erythropoietin (EPO) (25 UI/kg) three times a week and phlebotomy once a week, to prevent liver toxicity in a patient with advanced acute leukemia and liver disease due to severe iron overload, previous drug toxicity and hepatitis c viral infection. Over the 9 months prior to allogeneic HSCT, 34 phlebotomies were carried out. serum ferritin dropped from 2964 to 239 microg/l and the ALT dropped to near normal values. At allogeneic HSCT no liver toxicity was observed, suggesting that iron depletion in the pretransplant period may contribute to reducing transplant-related toxicity in selected cases.
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ranking = 1
keywords = leukemia, m
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2/431. Acute promyelocytic leukemia. New methods in diagnosis and treatment.

    Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by hypergranular leukemic cells, bleeding diathesis and t(15; 17) translocation. The t(15; 17) translocation leads to the production of the PML-RAR alpha fusion protein which plays a vital role in the pathogenesis of APL by arresting normal differentiation of myeloid precursors. However, in the presence of high concentrations of all-trans-retinoic acid (ATRA), the PML-RAR alpha fusion protein serves to stimulate cell differentiation. The diagnosis of APL and the detection of residual disease are based on the t(15; 17) translocation. Treatment with a combination of ATRA and anthracycline-AraC chemotherapy has shown a higher rate of complete remission in APL. We report the case of a 71-year-old male with the rare microgranular variant of APL to illustrate these findings. The patient was treated with a combination of ATRA and daunorubicin-AraC chemotherapy and achieved complete remission. He developed retinoic acid syndrome as a complication of therapy with ATRA. The methods for diagnosis, the molecular mechanisms in the oncogenesis of APL, rationale of treatment of APL with ATRA, complications of therapy and the new concepts in the treatment of ATRA-resistant APL are discussed.
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ranking = 6.0047435356034
keywords = leukemia, myeloid leukemia, m
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3/431. Development of acute promyelocytic leukemia with isochromosome 17q after BCR/ABL positive chronic myeloid leukemia.

    We describe a pediatric case of acute promyelocytic leukemia with an i(17q) after treatment of BCR/ABL positive chronic myeloid leukemia (CML) for 3.5 years. The patient was treated with Busulphan, alpha-2a interferon, hydroxyurea, and cytosine arabinoside at various times in the course of the chronic phase of CML, because he had no HLA-identical donor for bone marrow transplantation. Hematologic remission was achieved for a short time, but cytogenetic remission was never possible. When promyelocytic blast crisis was diagnosed according to the French-American-British classification, cytogenetic studies revealed an i(17q) as a new feature in our patient. The promyelocytic transformation was associated with the appearance of an i(17q) preceding CML are discussed in the light of recent literature.
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ranking = 10.02472880902
keywords = leukemia, myeloid leukemia, m
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4/431. Isovaleric acidemia with promyelocytic myeloproliferative syndrome.

    Isovaleric acidemia, an autosomal recessive disorder, is due to isovaleryl-coenzyme a dehydrogenase deficiency and is one of the branched-chain aminoacidopathies. Isovaleric acidemia may present in the neonatal period with an acute episode of severe metabolic acidosis, ketosis, and vomiting and may lead to coma and death in the first 2 months of life. This report concerns an infant who presented at 10 days of age because of lethargy, poor feeding, hypothermia, cholestasis, and thrombocytopenia, leukopenia, and profound pancytopenia. death occurred at 19 days of age. autopsy showed mild fatty change in the liver and extramedullary hematopoiesis, generalized escherichia coli sepsis, and myelodysplasia of the bone marrow with arrest of the myeloid series at the promyelocytic stage. The appearance resembled promyelocytic leukemia, but the diagnostic 15:17 translocation was not present. The maturation arrest in granulopoiesis in isovaleric acidemia appears to be most likely due to a direct metabolic effect on granulocyte precursor cells.
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ranking = 1.0000807366961
keywords = leukemia, m
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5/431. Acute promyelocytic leukemia after treatment for non-Hodgkin's lymphoma with drugs targeting topoisomerase II.

    We report a patient who developed acute promyelocytic leukemia (APL) concomitantly with a second relapse of non-Hodgkin's lymphoma (NHL), intermediate grade, WF type E. At diagnosis and at first NHL relapse, the patient had received the same chemotherapy regimen, which included drugs targeting dna topoisomerase II, i.e., etoposide (total dose 5,760 mg) and idarubicin (total dose 180 mg). Thirty-eight months after initial treatment, the patient showed pancytopenia associated with lymphoma recurrence. bone marrow examination revealed the presence of atypical promyelocytes with Auer rods; cytogenetics showed t(15;17), and molecular analysis detected promyelocytic leukemia-retinoic acid receptor alpha rearrangement. APL reached complete remission after all trans retinoic acid therapy, whereas NHL did not respond to further chemotherapy. In the literature, five other patients developed APL after treatment for lymphoma, from a total of 59 patients developing sAPL after treatment for any type of neoplasia.
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ranking = 5.9997039654478
keywords = leukemia, m
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6/431. Extramedullary disease in acute promyelocytic leukemia.

    All-trans retinoic acid (ATRA) is currently recommended as standard treatment for acute promyelocytic leukemia (APL). However there has been increasing concern that ATRA is associated with unusual sites of relapse. Although there is insufficient evidence so far to substantiate this, we review the potential mechanisms by which ATRA may increase the incidence of extramedullary and, in particular, central nervous system (CNS) relapse.
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ranking = 4.9996616747975
keywords = leukemia, m
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7/431. Identification of the t(15;17) in AML FAB types other than M3: evaluation of the role of molecular screening for the PML/RARalpha rearrangement in newly diagnosed AML. The Medical research Council (MRC) adult Leukaemia Working Party.

    Acute promyelocytic leukaemia (APL) is characterized by the t(15;17) leading to the formation of PML-RARalpha and RARalpha-PML fusion genes; this rearrangement has been considered both diagnostic for, and restricted to, this subtype of acute myeloid leukaemia (AML FAB M3). We describe two cases of AML with the t(15;17) associated with a PML/RARalpha rearrangement which lacked typical APL morphology, classified as FAB M1 and M2 respectively. In both cases morphological review revealed small populations of cells which exhibited some features associated with APL. In the case classified as M1, PML immunofluorescence studies revealed the classic microparticulate nuclear staining pattern as observed in typical cases of APL with the t(15;17). Similarly, blasts from this case were found to be sensitive to ATRA in vitro as determined by NBT reduction test and by normalization of the PML nuclear body staining pattern. To determine the frequency of PML/RARalpha rearrangements in FAB subtypes other than M3, 530 patients from the MRC AML trials were screened using nested RT-PCR. Only one individual, initially classified as M5 with a normal karyotype, was found to have a PML/RARalpha rearrangement. The diagnosis was revised to M3 variant on subsequent morphological review. In conclusion, this study demonstrates that, in rare cases, the t(15;17) is not restricted to patients with M3 morphology as defined by current FAB criteria. Therefore, although we consider cytogenetic analysis of newly diagnosed cases of AML to be mandatory, our data suggests that routine molecular screening for PML/RARalpha rearrangements is not justified and should be reserved for those cases displaying features which may be suspicious of APL even if such cells comprise only a minority of the total population.
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ranking = 0.0001691626012695
keywords = m
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8/431. Complex variant 15;17 translocations in acute promyelocytic leukemia. A case report and review of three-way translocations.

    Complex variant 15;17 translocations are increasingly recognized in acute promyelocytic leukemia (APL). We report a novel three-way translocation in APL involving chromosomes 15, 17, and X in the form of t(X;17;15)(q13;q12;q21). Southern blot analysis showed retinoic acid receptor alpha (RARA) gene rearrangement at intron 2. Clinical and morphologic findings are typical of APL, and a complete remission was attained with a course of conventional chemotherapy. A review of three-way complex variants of 15;17 translocation in the literature reveals 21 published cases in addition to ours. PML/RARA fusion was observed in all 8 cases in which molecular genetic analysis had been performed. More cases need to be analyzed to determine if clustering to particular chromosomal bands occurs in variant translocations, and whether APL cases harboring complex 15;17 variants differ clinically from those with classical 15;17 translocation.
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ranking = 4.9996962762386
keywords = leukemia, m
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9/431. Peripheral arterial occlusion in acute promyelocytic leukemia.

    A 16-year-old Caucasian teenager developed fatigue, abdominal pain, pneumonia, and subsequently acute vascular occlusion of the left superficial femoral artery. Vascular assessment and heparin therapy lead to bone marrow aspiration and a diagnosis of acute promyelocytic leukemia. Treatment with chemotherapy prevented loss of limb and avoided further vascular surgery. Young patients with acute vascular occlusion require an in-depth assessment including attention to hematological disorders. Clots obtained on thromboembolectomy should be sent for pathological assessment and not discarded, especially in an unusual-age patient for arterial embolus.
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ranking = 4.9996732086112
keywords = leukemia, m
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10/431. Atypical response to all-trans retinoic acid in a der(5)t(5;17) acute promyelocytic leukemia.

    Typical acute promyelocytic leukemia (APL) is associated with the t(15;17) translocation, expression of a PML/RARA fusion transcript, and responsiveness to all-trans retinoic acid (ATRA). Rare APL cases implicating the RARA but not the PML gene have been reported. Cases with t(11;17)(q23;q21) which fuses the PLZF and RARA genes do not respond to ATRA. In contrast, cases with t(11;17)(q13;q21) and t(5;17)(q35;q21) which fuse RARA with NuMA and NPM, respectively, were reported to be sensitive to ATRA. We described previously an APL case with an unbalanced t(5;17) implicating RARA but neither PML nor PLZF. Here, we show that in this case: (1) the NPM gene is not involved, as demonstrated by RT-PCR and Southern blot; (2) response to ATRA in vitro is atypical, as demonstrated by morphological and functional maturation assays; and (3) PML nuclear bodies are not disrupted, as evidenced by immunofluorescence staining.
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ranking = 4.9996462963792
keywords = leukemia, m
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