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    ABSTRACT: Several reports describe the association of hyperlymphocytosis with neutropenia. This syndrome, named lymphoproliferative disease, is characterized by a chronic indolent clinical course, bone marrow lymphocyte infiltration, and granulopenia of central origin. The proliferating lymphocytes share large granular lymphocyte natural killer cell and T-lymphocyte characteristics. They are either of monoclonal or polyclonal origin. In this report the familial occurrence of a similar syndrome observed in two children is described. Lymphocyte morphologic abnormalities including nuclear pockets, were noted, a feature usually present in leukemic cells. Lymphocyte proliferation was distinct in each case as shown by the presence of a predominant CD4+ cell population in one and a predominant CD8+ population in the other. Monoclonal gene rearrangements of T-cell receptor beta-chain gene were found although clonal variations occurred with time in one patient. The cause of this unique familial occurrence of monoclonal lymphoproliferation associated with neutropenia is unknown.
    Cancer 06/1991; 67(10):2610-7. · 5.20 Impact Factor
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    ABSTRACT: A series of 20 patients with granular lymphocyte proliferative disorders (GLPD) is reported. The criterion of inclusion was presence of persistent (6 months) granular lymphocytosis in the absence of any causative illness. Diagnoses made upon analytical control in half the patients of splenomegaly (25%) and hepatomegaly (25%) were infrequent. Clinical course was nonprogressive in 17/20 patients, but two developed high-grade NHL several years later and one showed progressive disease. Actuarial probability of survival at 5 years was 85%. Granular lymphocyte morphology was relatively homogeneous, and peripheral blood counts were preserved in the most patients. Bone marrow lymphocytic infiltration was low, as assessed by bone marrow aspiration and/or biopsy. Eosinophilia was an outstanding feature in eight cases. Ultrastructurally, all cases showed parallel tubular arrays; cytoplasmic granules and numerous short microvilli were noticed. The lymphoid phenotype was heterogeneous, the most common being CD2+CD3+CD4-CD8+, but six patients (30%) were CD4+ with variable expression of natural killer-associated antigens. Chromosomal analysis was abnormal in 4/10 patients [trisomy 19, t(5;6); inv(14) and inv(10)]. The study of -chain of the T-cell receptor revealed clonal rearrangements in 14 (78%), restricted to CD3+ patients (92%). In vitro culture of myeloid precursors showed decreased CFU-GM in 5/6 patients. Virological studies for HTLV-I and II were negative. In conclusion, the presence of a clonal proliferation was not correlated with the clinical course or an associated disease.
    Annals of Hematology 05/1994; 68(6):285-292. · 2.87 Impact Factor
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    ABSTRACT: A 27-year-old male patient with ataxia telangiectasia (AT) developed atypical chronic lymphocytic leukemia with increasing bone marrow infiltration in the absence of organomegaly. One-third of the leukemia cells expressed a mature suppressor/cytotoxic T cell phenotype (T3+ T4- T6- T8+ T10-), two-thirds demonstrated additional helper/inducer T cell-associated antigens (T3+ T4+ T6- T8+ T10-), and a small fraction reacted with a natural killer (NK) cell-specific monoclonal antibody (Leu 11+). The proliferative response to stimulation in vitro with lectins and various monoclonal antibodies resembled the proliferation pattern of mature thymocytes: The cells responded to phytohemagglutinin (PHA), concanavalin A (ConA), stimulation of the T3-Ti receptor complex with Sepharose-bound anti-T3, and stimulation of the sheep erythrocyte receptor protein with anti-T11(2) and anti-T11(3) in conjunction with exogenous interleukin-2 (IL 2); they failed, however, to proliferate after stimulation with anti-T11(2) and anti-T11(3) alone. There was no response in the mixed lymphocyte reaction (MLR) and no suppression of the MLR between two healthy donors. Antibody-dependent cell-mediated cytotoxicity and NK activity could not be demonstrated. Cytogenetic analysis revealed complex clonal aberrations, including an interstitial deletion of the long arm of chromosome 14 concerning bands q21-31, loss of chromosome 20, and loss of the Y chromosome. Cytostatic chemotherapy was of little use and caused serious side effects, whereas leukapheresis proved effective in reducing the tumor load. The clinical data and laboratory findings in this case correspond to three previously described patients with AT who developed chronic T cell leukemia. Thus, in adult patients with AT, malignant proliferation of cytogenetically marked and phenotypically heterogeneous mature T cells seems to be a frequent complication.
    Blood 09/1986; 68(2):577-85. · 9.78 Impact Factor