Cases reported "Preleukemia"

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1/13. Proliferative behavior of hemopoietic cells in preleukemia and overt leukemia observed in one patient.

    Hemopoietic cell proliferation was studied in a patient suffering from preleukemia characterized by peripheral pancytopenia and hypercellular bone marrow with ineffective erythropoiesis. Two years later when overt acute myelogenous leukemia had developed the study was repeated. The kinetics of proliferation were investigated by a new method which allows evaluation of the rate and time of dna synthesis in individual morphologically defined cells. erythropoiesis was found ineffective to the same degree in both stages of disease. The rate of erythroid cell proliferation, however, was reduced in overt leukemia only. The myeloid system showed a grossly reduced production rate of myeloblasts in preleukemia whilst the same parameter was strongly increased in leukemia. This high production rate of myeloblasts in overt leukemia was interpreted as indication of a far-reaching self-maintenance of the myeloblast pool in this stage of disease. The proliferative activity of the individual myeloblasts was reduced already in preleukemia, and even more so in leukemia. In order to explain the amplification of the myeloblast pool with the onset of overt leukemia a change in the mode of myeloblast divisions is assumed. For this a transition from steady state to some degree of exponential growth gives the most plausible explanation.
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2/13. Transient pancytopenia preceding acute lymphoblastic leukaemia (pre-ALL) precipitated by parvovirus B19.

    A preleukaemic phase, typified by pancytopenia and bone marrow (BM) hypoplasia, is an uncommon but well-documented prelude to acute lymphoblastic leukaemia (pre-ALL) in children. parvovirus B19 (B19) exhibits a marked tropism to human BM and replicates only in erythroid progenitor cells acting as a confounding, but treatable agent in immunocompromised patients. We present the first case of B19-associated pre-ALL characterized by severe and recurring transient pancytopenia in a child who developed ALL 5 months later. The advent of B19-specific IgG at the time of infection and the subsequent disappearance 1.5 years later has not previously been described. In this patient the observed cytopenias were probably the result of B19 acting in concert with the failing BM and B19 is possibly one of several factors capable of triggering the onset of pre-ALL.
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keywords = pancytopenia
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3/13. pancytopenia presenting with monosomy 7 which disappeared after immunosuppressive therapy.

    monosomy 7 syndrome in infant is considered as pre-leukemic condition of poor prognosis. However, it seems controversial recently, because some cases of monosomy 7 syndrome showed spontaneous remission. We report 2-year-old girl with severe pancytopenia, who presented with monosomy 7. Morphologically, there was little dysplasia in the trilineage hematopoiesis. monosomy 7 clone of CD34 positive cells, bone marrow mononuclear cells (BMMNC), and peripheral nuclear cells was 4.0, 40, and 3.8%, respectively. Immunosuppressive therapy was effective along with the disappearance of monosomy 7 clone. WT1 mRNA expression was not increased in monosomy 7 clone. Pathogenesis of monosomy 7 and its relation to aplastic anemia is discussed.
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4/13. bcr-abl-positive T-cell acute lymphoblastic leukemia associated with parvovirus B19 infection.

    The authors report an unusual presentation of a philadelphia chromosome-positive acute lymphoblastic leukemia with two unusual features: a bcr-abl fusion mRNA coding for p210 protein and a T-cell immunophenotype. The patient was a 16-year-old boy who presented with septic shock and pancytopenia, likely precipitated by an acute parvovirus B19 infection. Management consisted of supportive therapy, followed by chemotherapy for T-cell acute lymphoblastic leukemia and stem cell transplantation. He died 8 months after transplant due to idiopathic pneumonia syndrome, but without evidence of relapsed disease.
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5/13. Stimulation of nonclonal hematopoiesis and suppression of the neoplastic clone after treatment with recombinant human granulocyte-macrophage colony-stimulating factor in a patient with therapy-related myelodysplastic syndrome.

    A complete hematologic remission was achieved in a patient with therapy-related preleukemia and transfusion-dependent pancytopenia after treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). The patient remained in remission for nearly 1 year despite the discontinuation of GM-CSF treatment. Several lines of evidence suggest that normal hematopoiesis was restored after GM-CSF treatment. First, the cytogenetic anomaly, which was present before GM-CSF, completely disappeared after three cycles of treatment. Cytogenetic conversion was documented by conventional karyotypic evaluation of mitotic bone marrow cell preparations as well as by premature chromosome condensation analysis of the nonmitotic cells of bone marrow and peripheral blood. Second, the growth pattern and cycle status of bone marrow granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells were found to be normal during remission. Third, x chromosome-linked restriction fragment length polymorphism-methylation analysis of dna from mononuclear cells (greater than 80% lymphocytes) and mature myeloid elements showed a polyclonal pattern. These findings suggest that restoration of hematopoiesis in this patient after GM-CSF treatment may have resulted from suppression of the abnormal clone and a selective growth advantage of normal elements.
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6/13. Conversion of polycythemia vera to refractory anemia with hyperplastic bone marrow.

    Clinical and morphologic findings in the conversion of treated polycythemia vera to pancytopenia with hyperplastic bone marrow (refractory anemia or pancytopenia with hyperplastic bone marrow) are described in light of our own observation. The nomenclature associated with this condition (pancytopenia, chronic erythroleukemia, preleukemia) is not uniform, whereas the morphologic findings are virtually identical. Some patients subsequently develop acute leukemia. The prognosis in cases of refractory anemia with hyperplastic bone marrow following polycythemia vera is, independent of the subsequent acute leukemia, invariably terminal.
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7/13. preleukemia in Fanconi's anemia: hematopoietic cell multinuclearity, membrane duplication, and dysgranulogenesis.

    A 25-year-old male had Fanconi's anemia characterized by small stature, the onset of pancytopenia in the first decade of life, a high spontaneous breakage rate of the chromosomes, and the development of acute myeloblastic leukemia. In the preleukemic phase, marrow erythroblasts were multinucleated, and had duplicated nuclear and cytoplasmic membranes with frequent nuclear pockets and cytoplasmic vacuoles, respectively. All neutrophilic and eosinophilic granulocytes had severe quantitative and qualitative defects of granulogenesis; autophagy and nuclear pockets were also observed in the majority of granulocytic cells. Platelets had decreased granulation and extremely dilated canaliculi. Decreased titration scores with anti-I and anti-i were observed with the patient's erythrocytes and those of his clinically normal mother. The unusual morphologic and serologic findings in this patient appear to have resulted from a membrane abnormality affecting the cells of several hematopoietic lines and their organelles.
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8/13. Acute megakaryocytic leukemia. Description of a case initially seen as preleukemia syndrome.

    A 52-year-old man had aregenerative anemia unresponsive to pyridoxine hydrochloride. Acute leukemia developed, and he died four months after diagnosis. At autopsy he had acute megakaryocytic leukemia with involvement of bone marrow, liver, spleen, adrenals, kidneys, and thyroid. Chromosomal analysis revealed absence of both diploid and Ph1 chromosomes. A mode of 45 chromosomes and aneuploidy were present. This is similar to the only other case with chromosomal studies. Of the 15 acceptable documented cases, eight were men and seven were women. Their age varied from 28 to 76 (mean, 55) years. Only two were less than 40 years of age. Most had pancytopenia, and all were dead within six months of diagnosis.
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9/13. Restoration of normal hematopoiesis by bone marrow ablation and allogeneic marrow transplantation in a case of Hodgkin's disease therapy-related preleukemia.

    Therapy-related leukemias are generally preceded by a preleukemic phase of several months duration, characterized by pancytopenia, abnormal bone marrow findings, and nonrandom chromosomal abnormalities in almost all cases. No specific therapeutic guidelines are recommended in this preleukemic phase or any other type of preleukemia; aggressive combination chemotherapy is usually withheld until the full expression of leukemia. A 22-yr-old man with therapy-related preleukemia following treatment of Hodgkin's disease received as primary treatment ablative chemotherapy followed by marrow transplantation from his histocompatible sister. At day 316, the patient is still in complete bone marrow recovery with a normal donor karyotype. In the light of the very poor results obtained with conventional chemotherapy regimens once the leukemic phase is established, we suggest that bone marrow transplantation, if undertaken before leukemic conversion, may be the treatment of choice in young adults with therapy-related preleukemia.
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keywords = pancytopenia
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10/13. Hematologic and cytogenetic study of two cases of acute leukemia associated with breast cancer.

    The authors present two cases of patients with breast cancer with lymph node extension and who both had surgery. As a pancytopenia with hypercellular bone marrow was discovered at the same time in the first patient, she received no complementary treatment; 4 months later, she presented with an acute lymphocytic leukemia (ALL) for which a remission was easily induced, but she died of a pulmonary infection. The second patient received local radiotherapy (50 grays) and adjuvant chemotherapy (Alkeran for 26 months). Forty-seven months after the diagnosis of breast cancer and 16 months after the end of the treatment, an acute nonlymphoblastic leukemia (ANLL; M6) was diagnosed after 8 months of a preleukemic state. Treatment did not produce any results and death occurred on the 17th day. Cytogenetic studies on the bone marrow cells of both patients were performed. In the first patient in the ALL phase normal cells coexisted with a 47 chromosome clone, the extra chromosome being a D ( 13?). In the second patient, several karyotype abnormalities were already present in the preleukemic state and also during the acute leukemic phase. No normal mitoses were found; hypodiploidy was present as well as major abnormalities such as markers, rings, and, among others, the systematic loss of a #5 and a #7. The first patient seems to have presented with a de novo ALL, associated with the malignant tumor; whereas, the second patient showed all the characteristics of an induced ANLL. The clinical, hematologic, and cytogenetic characteristics of these two patients are analyzed and compared to those of other cases in the literature.
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