1/6. 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.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/6. 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.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/6. Imatinib mesylate in philadelphia chromosome-positive leukemia of childhood.BACKGROUND: Initial treatment for adult patients with philadelphia chromosome-positive (Ph[ ]) chronic myelogenous leukemia (CML) now includes imatinib mesylate. However, to our knowledge, there are few data regarding imatinib safety, efficacy, and response monitoring in patients age < 18 years. methods: In the current series, the authors report 5 consecutive patients ages 20 months to 12 years with Ph leukemia who were treated with imatinib and evaluated for a response using cytogenetics, fluorescent in situ hybridization (FISH), and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on serial bone marrow aspirations. Doses of imatinib were escalated as tolerated from a starting dose of 400 mg/m2 (patients with a body surface area [BSA] < 1 m2) or 400 mg/day (patients with a BSA > 1 m2). RESULTS: After the initiation of imatinib therapy, all 4 patients with CML were found to have no detectable Ph chromosome by cytogenetics (median of 198 days of imatinib therapy; range, 138-346 days), FISH (median of 285 days of imatinib therapy; range, 138-366 days), and real-time RT-PCR (median of 287 days of imatinib therapy; range, 224-366 days). One patient with Ph acute mixed lineage leukemia achieved a morphologic disease remission with standard chemotherapy, but within 10 months had increasing Ph positivity in consecutive bone marrow aspirations. Imatinib was added to the intensive leukemia therapy, and within 26 days there were no detectable Ph cells in the bone marrow. Mild thrombocytopenia was noted in two patients and transient mild hepatic toxicity was noted in one patient. CONCLUSIONS: Imatinib mesylate was found to be effective in inducing undetectable residual disease in a small cohort of pediatric patients with Ph leukemia. Further studies of the use of imatinib in childhood Ph malignancies are needed.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/6. 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.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/6. Case of chronic-phase chronic myelogenous leukemia with an abdominal hematopoietic tumor of leukemic clone origin.We report a 59-year-old man with chronic myelogenous leukemia (CML) in chronic phase who presented with a large abdominal tumor. biopsy revealed proliferation of granulocytic-, erythroid-, and megakaryocytic-lineage cells in a retroperitoneal lymph node. The BCR/ABL fusion gene was detected on a paraffin-embedded tissue section of the lymph node by double-color fluorescence in situ hybridization, indicating an extramedullary hematopoietic tumor of CML origin. This patient has achieved a complete cytogenetic response for 19 months with imatinib mesylate (STI571; Gleevec), in association with the regression of the tumor. However, the development of an extramedullary tumor in chronic-phase CML generally indicates a poor prognosis, because it commonly consists of blast proliferation and is followed by blast crisis in the marrow within a few months. This case, therefore, points to the importance of histological examination of extramedullary tumors in CML for evaluation of disease status and for therapeutic decisions.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/6. Durable molecular remission in a patient with chronic myelogenous leukemia and host-derived hematopoiesis after allogeneic bone marrow transplantation.A 44-year-old woman with Ph-positive CML was treated with TBI, splenic irradiation, Ara-C, and CY. She then received unmanipulated marrow cells from her HLA-identical brother. GVHD prophylaxis was FK506 and MTX. WBC counts reached 1000/microliter on day 28 when all metaphases of marrow cells showed 46XY. However, on day 42, 46XX was detected in two of 20 metaphases, and the percentage of cells with female karyotype subsequently increased. On day 519, all metaphases showed female karyotype. BCR-ABL mRNA and philadelphia chromosome were never detected throughout her post-transplant course. fluorescence in situ hybridization (FISH) revealed complete recovery of host-derived hematopoiesis in the bone marrow, however, mixed T cell chimerism in the peripheral blood. This suggests that the persistence of donor-derived T cells may prevent disease recurrence through graft-versus-leukemia effect. The patient remains in a molecular complete remission with host-derived hematopoiesis 749 days post-transplant.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |