Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I.

We describe five patients with adult T-cell leukemia/lymphoma (ATL) with neither integration of human T-cell leukemia virus type I (HTLV-I) into their leukemia cells nor anti-HTLV-I antibody in their sera. These findings indicate that HTLV-I may not have been involved in leukemogenesis in these patients. The clinicohematological, cytopathological, and immunological features of HTLV-I-negative ATL were exactly the same as those of HTLV-I-associated ATL. Leukemia cells with pleomorphic nuclei, generalized lymphadenopathy, hepatosplenomegaly, skin lesions, hypercalcemia, and elevated lactate dehydrogenase levels, all of which are characteristic features of typical ATL, were also seen in these patients with HTLV-I-negative ATL. Leukemia cells expressed T3, T4, and pan-T-cell antigens in three cases, and T3 and pan-T-cell antigens in two. All five patients had lived in ATL-nonendemic areas. The finding of HTLV-I-negative ATL suggests that factor(s) other than HTLV-I infection may be involved in ATL leukemogenesis.     

NIH conference. T-cell lymphoproliferative syndrome associated with human T-cell leukemia/lymphoma virus

Human T-cell leukemia/lymphoma virus is a unique family of T-cell tropic, human, type-C retroviruses. The discovery of this class of retroviruses provides the first proven link between retroviruses and cancer in humans. This virus is endemic in certain parts of the world, including the southeastern United States, and is associated with the development of adult T-cell leukemia/lymphoma, a fulminant lymphoproliferative disorder frequently accompanied by opportunistic infections and hypercalcemia. Over the last few years, major advances have been made in understanding the clinical, epidemiologic, molecular biologic, and immunologic features of this unique class of human RNA tumor viruses.     

Human T-cell leukemia/lymphoma virus: the retrovirus of adult T-cell leukemia/lymphoma

Human T (thymus-derived)-cell leukemia/lymphoma virus (HTLV) is a new retrovirus first isolated from T-cell lines from a patient with cutaneous T-cell lymphoma from the southeastern United States. Closely related viruses have since been isolated from several patients with adult T-cell leukemia and lymphoma (and some normal persons) from different areas of the world. HTLV is not a genetically transmitted endogenous virus of humans, but it rather is acquired by postzygotic infection. Natural antibodies to several purified viral proteins have been observed in infected individuals. HTLV is transmissible in vitro to human cord blood T cells, and infection results in an increased growth rate, a reduced requirement for (and often independence from) T-cell growth factor, and an abrogation of the crisis period that usually occurs a month after the establishment of normal T-cell cultures. These data suggest that HTLV is the etiologic agent in some human cases of leukemia and lymphoma.     

Gastric lymphoma associated with human T-cell leukemia virus type I

A 41-year-old woman presented with a gastric lymphoma. A total gastrectomy was performed, and the tumor was found to consist of T cells of the helper/inducer (E+, Leu-1+, Leu-2a-, Leu-3a+) phenotype. The patient was seropositive for T-cell leukemia virus type I, and the tumor cells contained the proviral genome.     

Epidemiology of human T-cell leukemia/lymphoma virus

Human T (thymus-derived)-cell leukemia/lymphoma virus (HTLV) is the first retrovirus consistently isolated from humans. Seroepidemiologic testing for antibodies to HTLV document the following. (1) HTLV is associated with a spectrum of mature T-cell lymphoreticular neoplasms. (2) HTLV is strongly associated with clusters of adult T-cell leukemia in Japan and a related syndrome, lymphosarcoma T-cell leukemia in the Caribbean. (3) Virus-positive infections from other areas of the world share similar clinicopathologic features, with some overlap with cutaneous T-cell lymphoma (CTCL). Antibodies to HTLV are lacking in most persons with CTCL. (4) Virus-associated malignancy clusters in geographic areas where HTLV infection is prevalent, and virus positivity varies by country, region within country, age, and possibly race and sex. Although preliminary, the epidemiologic data suggest that HTLV is etiologically linked to a specific subtype of mature T-cell malignancy.     

Familial adult T-cell leukemia/lymphoma

Clinical and laboratory data are described for two siblings who both developed adult T-cell leukemia/lymphoma resulting from infection by human T lymphotropic virus type I (HTLV-I). These findings suggest that genetic factors or virus-specific factors may determine which HTLV-I-infected individuals will develop leukemia.     

Case report: adult T-cell leukemia/lymphoma associated with recurrent strongyloides hyperinfection

Adult T-cell leukemia/lymphoma (ATLL) was demonstrated postmortem in a 47-year-old woman initially manifesting severe hypercalcemia and a vertebral compression fracture. Hyperinfection with Strongyloides stercoralis preceded the appearance of ATLL by several months and ultimately dominated the terminal course. Although HTLV-I and S. stercoralis commonly infect the same host, only three other cases of concomitant ATLL and hyperinfection have been reported in English. The apparent rarity of this association suggests that immunologic sequelae of ATLL do not predispose to dissemination and multiplication of Strongyloides. Observations pertinent to this conclusion are reviewed.     

How I treat adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of mature activated T cells caused by human T-cell lymphotropic virus type I. ATL carries a bad prognosis because of intrinsic chemoresistance and severe immunosuppression. In acute ATL, Japanese trials demonstrated that although combinations of chemotherapy improved response rate, they failed to achieve a significant impact on survival. Patients with chronic and smoldering ATL have a better prognosis, but long-term survival is poor when these patients are managed with a watchful-waiting policy or with chemotherapy. Recently, a worldwide meta-analysis revealed that the combination of zidovudine and IFN-α is highly effective in the leukemic subtypes of ATL and should be considered as standard first-line therapy in that setting. This combination has changed the natural history of the disease through achievement of significantly improved long-term survival in patients with smoldering and chronic ATL as well as a subset of patients with acute ATL. ATL lymphoma patients still benefit from chemotherapy induction with concurrent or sequential antiretroviral therapy with zidovudine/IFN. To prevent relapse, clinical trials assessing consolidative targeted therapies such as arsenic/IFN combination or novel monoclonal antibodies are needed. Finally, allogeneic BM transplantation should be considered in suitable patients.     

ATL (adult T-cell leukemia/lymphoma)

128 cases of ATL (adult T-cell leukemia/lymphoma) were divided into 3 subgroups, 70 cases of acute type, 19 cases of chronic type and 39 cases of lymphoma type, and their prognosis were evaluated. Median survival time from the onset of acute type using Kaplan-Meier method was 8 months, that of lymphoma type was 14 months and that of chronic type was 50 months. Median survival time from the start of treatment of acute type was 5 months, that of lymphoma type was 11 months and that of chronic type was 22 months. Relatively short median survival time of chronic type may be due to they had some duration with observation only at first. No significant elongation of survival time could be obtained when acute type was divided into 2 stages, before and after 1982. Twelve patients with non-Hodgkins' lymphoma unresponsive to the first line combination chemotherapy were treated with combination therapy with cis-dichlorodiammineplatinum (CDDP). Ten patients were evaluable for response (4 cases of CR, 6 cases of PR). To stop the HTLV-1 carrier mothers milk for giving their children seems to be effective method to decrease the occurrence of ATL in future.     

Ocular manifestations in adult T-cell leukemia/lymphoma

 Ocular manifestations of adult T-cell leukemia/lymphoma (ATL) are rare events. However, several ocular lesions which resulted from human T-cell leukemia virus type I (HTLV-I) infection have been reported, including direct infiltration of ATL cells, cytomegalovirus retinitis, and HTLV-I-associated uveitis (HAU). The aim of this study was to characterize ocular involvement in ATL and to correlate these lesions with HTLV-I proviral DNA integration. Three patients with acute-type ATL and ocular lesions were evaluated hematologically and ophthalmologically. Analysis of HTLV-I proviral DNA was carried out with a standard Southern blot technique using DNA from abnormal lymphocytes in peripheral blood. Two patients developed intraocular lesions located within intermediate and/or posterior segments which were caused by infiltration of ATL cells. Ocular lesions in one patient, which were localized to the anterior-intermediate segment, closely resembled those of HAU. Analysis of HTLV-I proviral DNA revealed multiple integrations in all three patients. The present study indicated heterogeneity in ocular manifestations of ATL. Multiple HTLV-I proviral DNA integrations may be associated with intraocular involvement in this disease. Received: 30 October 1996 / Accepted: 23 January 1997     

Kaposi's sarcoma in human T-cell leukemia virus type I-associated adult T-cell leukemia

Kaposi's sarcoma (KS) developed in a patient with human T-cell leukemia virus type I (HTLV-I)-associated adult T-cell leukemia who was treated with a short-term course of monoclonal antibody immunotherapy. The presentation was transient and temporally related to the underlying clinical course. The association of KS in an HTLV-I infected, but not human immunodeficiency virus (HIV)-infected, individual should alert investigators to the occurrence of KS in retroviral-associated diseases other than acquired immunodeficiency disease syndrome. Recognition of the similarities and differences between HTLV-I and HIV infections may provide insights concerning the angiopathogenesis of KS.     

The human T-cell leukemia/lymphoma virus, lymphoma, lytic bone lesions, and hypercalcemia

The human T-cell lymphoma (HTL) virus is a type C RNA tumor virus isolated from patients with malignancies of mature T cells. We report three patients with peripheral T-cell lymphoma, hypercalcemia, and antibodies to HTL virus. One patient presented with idiopathic hypercalcemia of 6 months' duration, two with striking lytic bone lesions, and two with circulating malignant lymphocytes. Malignant cells from all patients had surface markers characteristic of thymic-derived lymphocytes (T cells), and all patients had natural serum antibodies to disrupted HTL virus and to one or both viral structural proteins p19 and p24. Patients with adult peripheral T-cell lymphomas, particularly those that present with hypercalcemia and lytic bone lesions, may have antibodies to the type C RNA human tumor virus, HTL virus.     

Adult T-cell leukemia/lymphoma associated with unusual positivity of anti-ATLA (adult T-cell leukemia-cell-associated antigen) antibodies

A 56-year-old female was admitted because of generalized lymphadenopathy. Based upon histological findings of biopsied lymph node, malignant lymphoma, diffuse large cell type was diagnosed. The surface marker analysis showed that malignant cells were positive for CD4 and CD2 but negative for CD8. Although anti-ATLA (adult T-cell leukemia associated antigen) antibody was negative with the use of a gelatin particle agglutination method (P.A.), other methods such as an indirect immunofluorescence assay (I.F.), an enzyme-linked immunosorbent assay (E.I.A.) and a Western blotting assay revealed the positivity for anti-ATLA antibody. Adult T-cell leukemia/lymphoma (ATL/L) was confirmed by the presence of monoclonal integration of HTLV-I proviral DNA in biopsied specimen. This case, showing a pattern of P.A. (-) and I.F. (+), is extremely unusual, because I.F. and P.A. show highly close correlation. Thus, it is important to employ different methods for screening of anti-ATLA antibodies in the diagnosis of ATL/L.     

Hematopoietic progenitor cells from patients with adult T-cell leukemia- lymphoma are not infected with human T-cell leukemia virus type 1

The in vivo host range of human T-cell leukemia virus type 1 (HTLV-1) has not been definitively established. To determine if hematopoietic stem cells from patients with adult T-cell leukemia-lymphoma (ATL) are infected with HTLV-1, we used a clonogenic progenitor assay followed by the polymerase chain reaction for the detection of HTLV-1 DNA. In vitro growth characteristics of myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells among nonadherent T-cell-depleted bone marrow (BM) mononuclear cells (NA-T-MNCs) from 10 patients with ATL was not significantly different from those of HTLV-1-seronegative controls (P = .20); numbers of colonies per 1 x 10(5) NA-T-MNCs were 34.9 +/- 7.6 for CFU-GM and 39.0 +/- 12.5 for BFU-E in patients with ATL, whereas those were 32.1 +/- 9.5 for CFU-GM and 41.4 +/- 12.7 for BFU-E in normal controls. HTLV-1 DNA was not detected in individual colonies formed by CD34+ cells from any of the patients. Similarly HTLV-1 DNA was not detected in 1 x 10(3) CD34+ cells sorted on a fluorescence-activated cell sorter (FACS) from six patients with ATL studied. In contrast, HTLV-1 DNA was detected in BM mononuclear cells from all patients. These observations clearly indicate that hematopoietic progenitor cells from patients with ATL are normal in their colony-forming capacity and that CD34+ cells from patients with ATL are not infected with HTLV-1 in vivo.     

Human T-cell lymphotropic virus type I associated adult T-cell leukaemia/lymphoma in Taiwan Chinese

Twenty-five Chinese patients with human T-cell lymphotropic virus type I (HTLV-I) associated adult T-cell leukaemia/lymphoma (ATLL) were identified in Taiwan. No patients had been outside Taiwan and none were descendants of Japanese heritage. Their ages ranged from 28 to 71 years. There were 17 men and eight women. Main clinical and laboratory features at presentation were lymphadenopathy (16), skin lesions (11), hepatosplenomegaly (11), pulmonary lesions (11), hypercalcaemia (10) and bone marrow infiltration (14). Peripheral blood was characterized by leucocytosis with presence of pleomorphic abnormal lymphocytes but rare anaemia or thrombocytopenia. The clinical subtypes were acute in 15, chronic in three, smouldering in one, and lymphoma type in six. The immunophenotypes of the ATLL cells were characterized by the expression of CD2+, CD4+, CD7-, CD8- and CD25+. The overall prognosis was poor with a median survival of 5 months. The acute form had a significantly shorter survival (2 months) than lymphoma type (13 months). Susceptibility to various infections was common. Pulmonary complications accounted for 73% of the causes of death. The clinicopathologic features of ATLL in Taiwan are indistinguishable from those in HTLV-I endemic areas. The present series adds to the knowledge of the worldwide pattern of the disease.