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1/33. Persisting bone marrow aplasia following interferon-alpha combined with ara-C for chronic myelogenous leukemia.

    A 37-year-old man with a newly diagnosed chronic myelogenous leukemia received induction therapy with hydroxyurea and interferon-alpha, and maintenance therapy with low-dose ara-C and interferon-alpha. Subsequent to a rapid hematological remission, a continuously aggravating pancytopenia with bone marrow aplasia developed which persisted after withdrawal of maintenance therapy. bone marrow examination exhibited aplastic areas and residual hematopoiesis with impaired maturation; cytogenetically, there was a 100% persistence of philadelphia chromosome-positive metaphases. By allogeneic bone marrow transplantation, a complete reconstitution of hematopoiesis was achieved.
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2/33. Management of chronic myeloid leukemia during pregnancy with leukapheresis.

    We describe the successful treatment of a pregnant patient with chronic myelogenous leukemia in chronic phase by using only leukapheresis. Following 20 leukapheresis procedures initiated during the 13th week of gestation and performed over approximately 7 weeks, the patients white blood cell count dropped from 242,000/microl to 19,300/microl. The WBC remained stable over the ensuing 17 weeks until the time of delivery. The patient gave birth by cesarean section to a healthy 2,640 g boy at 37.5 weeks of gestation. This is the second report of the successful use of leukapheresis alone for chronic myelogenous leukemia in chronic phase during the first half of pregnancy. We conclude that where leukapheresis is available, it may provide an alternative treatment to chemotherapy or alpha-interferon, especially in light of their potential teratogenic and leukemogenic side-effects.
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3/33. Ph-negative non-Hodgkin's lymphoma occurring in chronic phase of Ph-positive chronic myelogenous leukemia is defined as a genetically different neoplasm from extramedullary localized blast crisis: report of two cases and review of the literature.

    This report describes two cases of philadelphia chromosome-negative (Ph(-)) non-Hodgkin's lymphomas (NHLs) recognized in patients with chronic phase Ph-positive (Ph( )) chronic myelogenous leukemia (CML). Lymph node biopsy of patient 1 was initially diagnosed as diffuse large B cell non-Hodgkin's lymphoma (NHL, T cell rich variant), but at relapse showed immunoblastic features with a marked decrease of admixed lymphocyte components. Patient 2 presented with thickened parietal pleura which revealed a CD30-positive anaplastic large cell lymphoma showing null cell phenotype and genotype with abundant admixed neutrophils and lymphocytes. At the time of lymphoma diagnosis, the patients had CML for 33 and 10 months, respectively. dna obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell receptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT-PCR analysis, respectively. However, both biopsy specimens also contained reactive lymphocytes and neutrophils, and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either case by fluorescence in situ hybridization (FISH). These data suggest the lymphoma cells in both cases were not genetically associated with BCR/ABL. Therefore, these cases were not diagnosed as an extramedullary localized blast crisis in CML, but as Ph(-) NHLs. This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway, lacking BCR/ABL, in patients with Ph( ) CML. A review of the literature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of CML. The most common are T cell lymphomas displaying an immature thymic phenotype, while peripheral B cell lymphomas are more rare. Our study shows, however, that 'Ph( ) NHL' occurring in CML or acute lymphocytic leukemia (ALL) may represent an unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph( ) chromosome, and that FISH is required to confirm whether a localized lymphoid neoplasm is either a true extramedullary localized blast crisis or genetically distinct neoplasm. leukemia(2000) 14, 169-182.
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4/33. A case of near-triploidy in chronic myelogenous leukemia.

    A 61-year-old woman with chronic myelogenous leukemia (CML) in accelerated phase had a near-triploid bone-marrow karyotype. This karyotype is an unusual finding in CML, as we review 12 previously published similar cases. These patients do not differ clinically from other patients with CML in blast crisis. The cytogenetic features of near-diploid and near-triploid CML are similar, except that relative loss of chromosomes is more common and that isochromosome 17q has not been reported in near-triploid CML.
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5/33. Fatal invasive cerebral absidia corymbifera infection following bone marrow transplantation.

    A 56-year-old dairy farmer received a fully HLA matched unrelated donor marrow transplant for high risk CML in chronic phase. His early post-transplant course was complicated by a series of massive intracerebral bleeds and by sepsis related to a malignant otitis externa. The microbial pathogen isolated from ear swabs was found to be absidia corymbifera, but CT scan at the time showed no intracerebral extension. Despite neutrophil engraftment and aggressive antifungal management he succumbed. autopsy revealed invasion of absidia into the brain from the ear. We speculate that colonisation by absidia resulted from occupational exposure.
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6/33. Lethal adenovirus infection in a patient who had undergone nonmyeloablative stem cell transplantation.

    We present a case of adenovirus (ADV) infection in a patient who had undergone nonmyeloablative stem cell transplantation (NST). A 50-year-old man with chronic myelogenous leukemia in the second chronic phase underwent NST from an HLA 2-loci-mismatched sibling. ADV hemorrhagic cystitis developed and progressed to lethal pneumonia. ADV was isolated from urine, bronchoalveolar lavage fluid, and postmortem specimens of kidney and liver. Because there are few reports of lethal pneumonia associated with ADV in japan, we present the case and discuss the cause of and therapy for the infection.
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7/33. Hematologic and cytogenetic remission by STI571 (Glivec) in a patient relapsing with accelerated phase CML after second allogeneic stem cell transplantation.

    We describe the clinical activity of the ABL kinase inhibitor STI571 in a patient with accelerated phase of chronic myeloid leukemia (CML) relapsing after a second allogeneic BMT and with minimal levels of donor chimerism. STI571 resulted in rapid elimination of leukemic cells with ensuing prolonged severe leukopenia and neutropenia complicated by neutropenic fever and colitis. Subsequent hematopoietic recovery was driven by donor derived cells and was associated with grade 3 graft-versus-host disease (GVHD). STI571 induced sustained hematological and cytogenetic remission combined with controllable GvHD, therapeutic goals not achieved by two preceding allogeneic transplants and repeated donor lymphocyte transfusions (DLT).
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8/33. Acute leukostasis pulmonary distress syndrome.

    A 75-year-old woman in accelerated-phase chronic myeloid leukemia with hyperleukocytosis presented with acute respiratory distress syndrome. Despite early and aggressive pulmonary support and cytoreductive chemotherapy, the patient died. autopsy confirmed the presence of the leukostasis syndrome. The clinical, radiologic, pathophysiologic, and therapeutic aspects of this entity are reviewed.
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9/33. Complex translocation involving Ph chromosome in a patient with typical chronic myelogenous leukemia.

    We report a cytogenetic study of a patient with chronic myelogenous leukemia (CML) who, while displaying a Philadelphia (Ph) chromosome, resulting from a standard t(9;22) at diagnosis, during the chronic phase (CP) showed disappearance of the Ph and occurrence of new chromosome changes, including a marker probably arising from a translocation involving chromosome 17 and the Ph. in situ hybridization confirmed the cytogenetic appearance and demonstrated that the breakpoint on the Ph marker occurred below the BCR-ABL fusion gene.
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10/33. Sweet's syndrome with CML cell infiltration of the skin in a patient with chronic-phase CML while taking Imatinib Mesylate.

    Sweet's syndrome (acute febrile neutrophilic dermatosis) is characterized by an acute onset of erythematous plaques, fever, and leukocytosis. This syndrome has been reported to be associated with leukemia including chronic myelogenous leukemia (CML). Sweet's syndrome seen in patients with leukemia is usually associated with active and/or refractory disease. Imatinib Mesylate (STI-571, Gleevec) is widely used for therapy of CML. In this case report, CML cell infiltration of the skin was documented by fluorescence in situ hybridization (FISH) analysis in a patient with chronic-phase CML on Imatinib Mesylate (STI-571, Gleevec), who was at the time in molecular remission.
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