Cases reported "Blast Crisis"

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1/24. blast crisis of chronic myelogenous leukemia exhibiting immunophenotypic features of a myeloid/natural killer cell precursor.

    We report a patient with philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) which transformed into blast crisis bearing the immunophenotypic features similar to those of the myeloid/natural killer (NK) cell precursor leukemia we proposed previously. Using a CD45 blast gating method, the myeloperoxidase-negative blasts were positive for CD7, CD13, CD33, CD34, CD56, and HLA-DR, but no other lymphoid antigens. Southern blot analysis showed germ line T cell receptor beta and delta genes and immunoglobulin heavy and light chain genes. Although NK cell blastic transformation with Ph1 positive CML has been reported in a single patient, this is, to our knowledge, the first report of CML blast crisis of myeloid/NK cell precursor origin.
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2/24. Acute blast crisis with EBV-infected blasts, in a patient with chronic myeloid leukemia, and vasculitis.

    Unless they undergo transplantation, all patients with chronic myeloid leukemia (CML) will eventually develop a late phase of acute blast crisis (ABC). Although additional chromosomal abnormalities to the Philadelphia (Ph) chromosome may herald ABC in many CML cases, the mechanisms leading to this fatal event are obscure. Viral etiology, including the Epstein-Barr virus (EBV) has never been implicated in the pathogenesis of ABC in CML. iloprost is an analogue of epoprostenol (prostacyclin; PGI2) commonly used for the treatment of peripheral vascular diseases and acts via inhibition of platelet activation, and by vasodilation. A case of ABC with blasts of undetermined lineage showing EBV infection in a male patient with Ph positive CML is described here. This unusual event developed during a course of treatment with the prostacyclin analogue, iloprost administered for vasculopathic leg ulcers. The proliferating blasts stained positively by immunohistochemistry only for the leukocyte common antigen (LCA/CD-45), and the EBV-latent membrane protein 1 (LMP-1). The only chromosomal abnormality detected by cytogenetic analysis was the conventional Ph-chromosome. It is suggested that ABC in this case of CML, was associated with EBV-activated blasts of undetermined lineage.
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3/24. Expression of NK-associated antigens in extramedullary lymph nodal blast crisis of chronic myeloid leukemia on fine-needle cytology.

    A case is reported of a 62-yr-old male suffering from chronic myelogenous leukemia (CML) who developed an extramedullary, para-orthic lymph-nodal blast crisis without blood or bone marrow involvement and expression of CD56/NK associated marker. The diagnosis was performed on ultrasound-guided fine-needle cytology by an immunocytochemical and flow cytometric analysis. Conventional smears showed a monomorphous population of disperse, undifferentiated cells without cytoplasm. Cells showed fragile nuclei, vesicular chromatin, and evident nucleoli. Immunocytochemistry performed on cytospin slides were negative for cytokeratin, LCA, CD20, CD45Ro, and myeloperoxidase (MPO). flow cytometry analysis proved the myeloid origin of the tumor by expression of CD13, CD34, and CD38 and showed aberrant expression of CD56. Cytological diagnosis was confirmed by histological examination. CD56 expression is generally an expression of NK lymphoid proliferation and may be observed in acute myelogenous leukemia but has rarely been reported in CML and its related blast crisis. This unusual expression, its possible explanation, the related technical problems, and clinicopathological aspects are discussed.
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4/24. A case of biphenotypic blast crisis of unclassified myeloproliferative disorder.

    We report a first case of biphenotypic blast crisis of unclassified myeloproliferative disorder (MPD). A 20-year-old patient presented with fever, splenomegaly, marked leukocytosis (603 x 10(3)/ micro l), and blasts in the peripheral blood. Since Ph chromosome and bcr-abl gene rearrangement were absent, the diagnosis of an unclassified MPD in the blast crisis phase was established. immunophenotyping confirmed a biphenotypic crisis of myeloid and T-lymphoid antigens. The patient went into a complete remission after chemotherapy, but marked granulocytic hyperplasia (M:E ratio of 5.7) and 90% cellularity remained. blast crisis recurred during subsequent intensification chemotherapy and the patient did not go into a complete remission regardless of the intense chemotherapy. The blast crisis transformed from unclassified MPD had a grave prognosis as it responded poorly to chemotherapy. This unique blast crisis is distinguishable from the blast crisis of chronic myelogenous leukemia.
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5/24. Extramedullary blast crisis of chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation mimicking aggressive, translocation t(14;18)-positive B-cell lymphoma.

    We report the case of a 42-year-old male patient who was diagnosed with a large tumor of the right thoracic aperture 30 months after unrelated hematopoietic stem cell transplantation (HSCT) for accelerated phase of philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML). biopsy revealed an immature lymphoid neoplasia with blastic tumor cell morphology and immunoreactivity for CD34, CD79a, CD43, and CD30 as well as slight positivity for TdT and CD20. Bcr-Abl rearrangement was found in interphase tumor cell nuclei by fluorescence in situ hybridization (FISH). Furthermore, a translocation t(14;18)(q32;q21) was amplified by polymerase chain reaction (PCR). bone marrow (BM) examination showed regular hematopoiesis including a negative FISH analysis for Bcr-Abl and complete donor chimerism. Nested PCR from peripheral blood (PB), but not conventional PCR, was positive for the b3a2 Bcr-Abl transcript. Neither radiation nor intensive chemotherapy was capable of achieving a tumor remission, and the patient died from progressive disease 6 months later. Postmortem examinations showed a shift of immunophenotype with appearance of myeloperoxidase-positive tumor cells and loss of lymphoid antigens. In addition, there were characteristic cytogenetic findings of multiple Ph chromosomes and a clonal loss of P53 tumor suppressor gene. The latter was already deleted before HSCT. We conclude that lymphoid neoplasia occurring in our patient should be interpreted as an extramedullary, very immature blast crisis of CML expressing lymphoid differentiation markers rather than a true de novo NHL.
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6/24. Rapid improvement of disseminated intravascular coagulation by donor leukocyte infusions in a patient with promyelocytic crisis of chronic myelogenous leukemia after reduced-intensity stem cell transplantation from an HLA 2-antigen-mismatched mother.

    Donor leukocyte infusion (DLI) is recognized as effective therapy for relapse after stem cell transplantation in patients with chronic myelogenous leukemia (CML). However, the clinical efficacy of DLI in the advanced phase of CML or other types of leukemia has not been clearly defined because of its varying degree of success. We describe a 22-year-old male patient with promyelocytic crisis of CML who had a relapse after peripheral blood stem cell transplantation, under reduced-intensity conditioning, from his HLA 2-antigen-mismatched mother. Complete hematologic remission was obtained after transplantation. However, a relapse that occurred on day 66 posttransplantion was characterized by an increase in number of leukemic promyelocytes with simultaneous exacerbation of disseminated intravascular coagulation (DIC). The patient received DLI containing 1 x 10(7)/kg CD3 cells on day 73. Because rapid improvement of DIC paralleled the decrease in leukemic cells and because it was observed soon after DLI and before the development of acute graft-versus-host disease (GVHD), we hypothesized that leukemia-specific cells other than natural killer cells or cytotoxic T-cells unrelated to GVHD played a role in the graft-versus-leukemia effect observed in our patient. In addition, this may be the first report of effective correction of DIC by DLI after stem cell transplantation.
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7/24. Lymph node blast crisis in chronic myeloid leukemia mimicking T-immunoblastic lymphoma.

    BACKGROUND: Chronic myeloid leukemia arises from a somatic mutation in a pluripotent stem cell. It generally terminates with a blastic crisis (BC). One third of BC are lymphoid, and most have a pre-B phenotype. Few cases of T-lymphoid BC have been reported. Here we describe a lymph node blast crisis mimicking T-immunoblastic lymphoma. methods: bone marrow and lymph nodes were histologically examined by standard methods and by an immunoperoxidase technique. Cytogenetic studies were also performed on lymph node and blood cells. Analysis of T-cell receptor genes and BCR rearrangements were performed on dna extracted from both frozen bone marrow and lymph-node cells. RESULTS: Lymph-node histology showed an infiltration by large lymphoid blasts, consistent with a diagnosis of immunoblastic lymphoma. Blast cells were CD2, CD7, TDT positive, and negative for myeloid and mature lymphoid antigens. The Ph1 chromosome was found in both bone marrow and lymph-node cells. BCR rearrangement was found in the dna from both bone marrow and lymph-node cells. TCR genes were not rearranged. DISCUSSION: The present study provides strong evidence that the lymph-node blast crisis of CML can assume the morphological appearance of immunoblastic lymphoma and may retain the immunological phenotype and genetic features of early T cells with BCR rearrangements.
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8/24. CD79a expression in acute myeloid leukemia t(8;21) and the importance of cytogenetics in the diagnosis of leukemias with immunophenotypic ambiguity.

    Acute leukemias that express antigens associated with more than one lineage have been classified as acute lymphocytic leukemia with myeloid markers, acute myeloid leukemia with lymphoid markers, or biphenotypic acute leukemia (BAL). Antibody to cytoplasmic CD79a has been recently introduced to flow cytometry. CD79a functions in and has a high degree of specificity for B-cell differentiation. It has only recently begun to be reported in biphenotypic acute leukemias. Cases of acute leukemia submitted to the flow cytometry laboratory were retrospectively reviewed beginning from the time analysis for cytoplasmic CD79a was added to leukemia and lymphoma panels. Among 89 cases of AML, 2 showed strong coexpression of CD79a. Both cases were differentiated FAB AML-M2 and demonstrated the t(8;21) with cytogenetics and the AML1/ETO rearrangement with fluorescence in situ hybridization (FISH). These are recurring abnormalities in FAB AML-M2. The immunophenotyping met proposed scoring criteria for a diagnosis of BAL. Nevertheless, the cytogenetic and FISH findings indicate that CD79a, despite its specificity for B-cell differentiation, represented the aberrant presence of a B-cell antigen in leukemias of distinct myeloid linage. It is doubtful that, in this setting, CD79a expression should be considered a manifestation of lineage ambiguity.
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9/24. A new murine monoclonal antibody for the diagnosis of erythroleukemia.

    The authors have developed a murine monoclonal antibody, RC-82.4, against an antigen expressed by a human erythroleukemia cell line OCI-MIR. The antibody reacts with an antigen expressed by proerythroblasts, normoblasts, and some reticulocytes but not expressed in erythrocytes, granulocytes, monocytes, megakaryocytes, plasma cells, or lymphocytes. The authors have established an immunocytochemical method for studying bone marrow smears with RC-82.4. By studying bone marrow smears from 11 patients with M-6 erythroleukemia and 104 patients with various other hematologic and nonhematologic malignancies, the authors have found that RC-82.4 has great sensitivity and specificity in recognizing erythroid differentiation in blasts. The authors have used RC-82.4 and antihemoglobin antibodies to identify erythroblasts in acute and secondary acquired cases of erythroleukemia that would have been unclassifiable by morphologic and all other conventional cytochemical and immunocytochemical criteria.
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10/24. Mixed blasts crisis following extramedullary involvement with the cytogenetic evidence of clonal evolutions in philadelphia chromosome-positive chronic myelocytic leukemia.

    We describe a unique case of a young girl with adult type chronic myelocytic leukemia (CML). Clinically she had an extramedullary blastic crisis (BC) prior to that in peripheral blood and in bone marrow. The blasts were primitive cells and always CD7, CD33, CD34 and HLA DR-positive. During the course of illness the blasts became negative for CD5 and positive for CD41a and for platelet-peroxidase. Additional chromosomal appearances and subsequently clonal evolution were seen during the clinical course. Surface antigen modulation and morphological changes, which were observed by microscopic examination and flow cytometry, were induced by in vitro incubation. Surface antigen modulation was more induced in the presence of phytohemagglutinine-conditioned media (PHA-CM) but the effects of PHA-CM on morphological changes were not clear.
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