Human T-lymphotropic virus type I-associated benign transient immature T-cell lymphocytosis.

We describe a case of human T-lymphotropic virus type I (HTLV-I)-associated transient benign immature T-cell lymphocytosis in a black female patient, which over the course of several months underwent spontaneous complete remission. The patient presented with a white blood cell count of 20,000/microliter and a T4/T8 ratio of 1.7:1. The majority of cells appeared to be lymphoid in origin, and cell marker analyses established that the circulating lymphocytes were predominantly immature T-cells. HTLV-I was detected at this time by a p19 indirect immunofluorescent slide assay. Over a 1-month period of time the patient's clinical status evolved into a mature T-lymphocytosis with a T4/T8 ratio of 4.5:1. HTLV-I was detected by anti-p19 immunofluorescence by cell sorter analyses and by dot-bloc nucleic acid hybridization. Serological testing demonstrated that the patient had anti-HTLV-I antibodies and antimembrane antibodies specific for an HTLV-I producing cell line. In a competitive HTLV-I ELISA assay only HTLV-I proteins could effectively compete out the seroreactivity. The patient also had a high serum level of soluble interleukin-2 (IL-2) receptors, which is associated with HTLV-I infection. This is the first reported case of immature T-lymphocytosis in a patient infected with HTLV-I. The patient's HTLV-I markers disappeared with time, and her lymphocytosis subsequently spontaneously resolved. She remains disease free and virus negative after 2 years of follow-up study.

Quantitative assay of human T-cell leukemia/lymphoma virus transformation.

The in vitro transformation of normal T-lymphocytes by human T-cell leukemia/lymphoma virus (HTLV-I) is possible utilizing cocultivation techniques. We now report on a quantitative assay for HTLV-I transformation. Transformed cell lines were produced by cocultivation of either preactivated (phytohemagglutinin and T-cell growth factor) or nonactivated peripheral blood mononuclear cells with an equal number of lethally irradiated HTLV-I-positive donor cells (MT-2). After 14 days in liquid culture, transformed cells were plated in a 2-layer soft agarose system with or without T-cell growth factor (TCGF). Colony formation among 50 normal controls was observed at varying efficiencies with a mean number of 179 colonies (range, 6-599) in the presence of TCGF (up to a 2-log difference). The day 14 T-cell cultures demonstrated relatively low colony-forming efficiencies (less than or equal to 0.1%) and enhanced colony formation in the presence of TCGF. Day 14 after cocultivation was chosen for this assay based on a dose-response relationship between colony formation and the virus-positive donor cell inoculum and the known kinetics of colony growth of normal activated T-cells. An analysis of individual colonies indicated that they were of target cell origin and HTLV-I positive. Recombinant beta-interferon in increasing concentrations caused a decrease in colony formation as measured in this assay. Long-term cell cultures (2-18 months) showed higher colony-forming efficiencies (up to 1.0%) which were not enhanced by TCGF. The ability to quantitatively evaluate transformation via colony counts will provide an opportunity to study differences in transforming efficiencies attributable to varying target cells, donor cells, or blocking factors such as interferons, drugs, or anti-HTLV-I antibodies.

Antibodies to human T-cell lymphotropic virus-I membrane antigens and inverted T4/T8 ratios in hemophiliacs.

Antibodies to the membrane antigens of human T-cell lymphotropic virus-I (anti-HTLV-MA) have been detected in patients with the acquired immune deficiency syndrome (AIDS) and in patients with hemophilia. The authors examined sera from 71 AIDS patients and 46 hemophiliac children for the presence of anti-HTLV-MA using an indirect membrane immunofluorescence assay with flow cytometry analysis. Thirty-seven of the 71 (52%) AIDS patients and 7 of the 46 (15%) hemophiliac patients had high titered anti-HTLV-MA, using a T-lymphoid cell line infected with the leukemia virus. None of the 78 control subjects had high titered antibody. All seven hemophiliac patients with elevated anti-HTLV-MA used Factor VIII concentrates, and all had inverted T-lymphocyte helper-suppressor (T4 [Leu-3]/T8 [Leu 2]) ratios. No correlations were found between inverted T4/T8 ratios and antibody to cytomegalovirus, Toxoplasma gondii, or hepatitis B. This work supports contentions that HTLV-like organisms cause AIDS and that these organisms are transmitted by blood products such as Factor VIII concentrate.

Inverse relationship between constitutive gamma interferon production and human T-cell lymphoma/leukemia virus expression in cultured T lymphocytes.

Particular interest in human T lymphocyte lymphoma/leukemia virus (HTLV) derives from the close association of HTLV with several types of human mature T lymphocyte malignancies and the strong possibility that HTLV is the causative agent of this group of leukemias and lymphomas. This is the first report to show that HTLV expression in T lymphocytes cultured in vitro is inversely proportional to constitutive gamma interferon production. Of 16 fresh T lymphocyte cultures established from patients with mature T lymphocyte neoplasias, 3 were grown continuously for over 3 years and 13 were grown for 2 to 8 months in culture. Of the 16 cultures, 9 were HTLVp19 positive and interferon negative, whereas the remaining 7 were HTLVp19 negative or weakly positive and also interferon positive (12 to 105 U/ml). The prototype HTLV-positive T-cell line (HUT102) was examined over a long-term culture and after selective cell cloning for high virus yield. Results indicate that early-passage, low-HTLV-producing HUT102 cells constitutively produced significant levels of gamma-immune interferon. In late-passage and cloned HUT102 cells, an increase in HTLV production was concordant with a decrease in constitutive interferon production and the loss of mature T lymphocyte antigens. Transformation of human umbilical cord blood lymphocytes by HTLV was possible only after cocultivation with the non-interferon, high virus-producing, cloned HUT102 T lymphocytes. The inverse relationship between interferon and HTLV production was also observed when normal human umbilical cord blood and adult T lymphocytes were transformed by HTLV and maintained in culture.

Non-Hodgkin's lymphoma limited to the larynx.

A case of primary laryngeal non-Hodgkin's lymphoma is detailed, with a review of the reports in the English literature on this rare site of presentation. Symptoms at onset generally include hoarseness, and may be observed up to 60 months prior to diagnosis. Four of the five cases classified by the Rappaport system are of diffuse histology. The histologic distinction of true lymphoma from pseudolymphoma, which may mimic lymphoma both grossly and microscopically, is reviewed. Local radiotherapy is a curative treatment of choice, with 16 of 18 cases disease-free throughout follow-up.

Splenectomy for thrombocytopenia in chronic lymphocytic leukemia.

The role of peripheral platelet destruction as a reversible etiology of thrombocytopenia in chronic lymphocytic leukemia (CLL) was evaluated in nine patients with CLL and refractory thrombocytopenia who underwent splenectomy. The patients' ages ranged from 54 to 74 years. Progressive thrombocytopenia refractory to antineoplastic agents and corticosteroids had been present for a mean of 23.4 months. The platelet counts were 4,000-57,000/microliter, and were generally higher in those patients with larger spleens. The spleens ranged from 180 to 4050 gm. Seven patients responded completely to splenectomy, achieving platelet counts greater than 150,000/microliter, and in one other patient, the count rose to greater than 100,000/microliter. The platelet count of one patient failed to respond to surgery. Those patients with massive splenomegaly developed higher, more rapidly rising platelet counts postoperatively. No operative mortality was encountered. Median hospitalization was seven postoperative days. All patients experienced an increased sense of well-being. Median follow-up time is 9 months.