HTLV-1 carriers with B-cell lymphoma of localized stage head and neck: prognosis, clinical and immunopathological features.

Human T-lymphotropic virus type I (HTLV-I) is closely associated with T-cell lymphoma/leukaemia, which always shows monoclonal HTLV-1 provirus DNA integration. HTLV-1 is not associated with B-cell lymphoma. The relationship between B-cell lymphoma and HTLV-1 was analysed retrospectively in early stage B-cell non-Hodgkin's lymphoma (NHL) according to HTLV-1 infection and pathological features. We analysed 198 cases of head and neck B-cell NHL treated with radiotherapy and/or chemotherapy; 21 were seropositive and 177 were seronegative for HTLV-1. We also immunostained 26 cases of diffuse large B-cell lymphoma (DLBL), including 12 seropositive and 14 seronegative for HTLV-1 respectively, for CD20, CD3, CD4, CD8, CD56, MIB-1 and T-cell-restricted intracellular antigen (TIA-1) to examine the phenotype, immunity and proliferation activity. The 5-year overall survival rates were 78% and 49% (P = 0.007, log rank test) for HTLV-1 seronegative and seropositive cases respectively. Infection with HTLV-1 was significantly associated with poor survival in patients with B-cell lymphoma by multivariate analysis. For DLBL, HTLV-1 infection was not a significant factor, but the overall survival curve was similar to that of the 21 seropositive B-cell lymphoma cases. Lymphoma cells were negative for TIA-1, but the background lymphocytes were positive for this marker. The number of TIA-1-positive cells was higher in HTLV-1-negative cases than in-positive cases. In conclusion, patients with B-cell-NHL (B-NHL) who are also HTLV-1 carriers have a poorer prognosis than non-carriers. HTLV-1 does not seem to be associated with lymphomagenesis of the B phenotype itself, but correlates with host immunity by reducing the number of cytotoxic T-cells.

Association of primate T-cell lymphotropic virus infection of pig-tailed macaques with high mortality.

Natural infection of humans with human T-cell lymphotropic virus type I (HTLV-I) and of old world nonhuman primates with the simian counterpart, STLV-I, is associated with development of neoplastic disease in a small percentage of individuals after long latent periods. HTLV-I is also the etiologic agent of a more rapidly progressive neurologic disease, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Macaques have been used experimentally in studies to evaluate HTLV-I candidate vaccines for efficacy, but no evidence of disease was observed. Here we report experimental infection of pig-tailed macaques with STLV-I(sm) and HTLV-I(ACH), both of which were associated with a disease syndrome characterized by rapid onset, hypothermia, lethargy, and death within hours to days. Other pathologic sequelae included diarrhea, rash, bladder dysfunction, weight loss, and, in one animal, arthropathy. Both retroviruses were detected in the central nervous systems of some animals, either by culture or by direct antigen capture for p19 Gag in cerebrospinal fluid. Although virus was recovered throughout infection from peripheral blood mononuclear cells (PBMC), all infected macaques maintained low antiviral antibody titers and stable proviral burdens, which generally ranged between 10 and 100 copies per 10(6) PBMC. However, of 13 macaques infected with HTLV-I(ACH) or STLV-I(sm), seven animals (54%) died between 35 weeks and 412 years after infection. This unexpected high mortality within a relatively short time suggests that infection of pig-tailed macaques might be a useful model for studying immune responses to and pathologic events resulting from HTLV-I infection.

[Possible long-term prognosis in epidemiologically significant virus infections]. / Mögliche Langzeitprognose bei epidemiologisch bedeutsamen Virusinfektionen.

The long-range prognosis of viral diseases must be assessed differently according to their geographical occurrence. The genetic disposition, environmental factors and additional infectious diseases play a decisive part here. Vaccinations are the most important measures in the prevention of these infections. The spectrum of possible chemotherapeutic intervention for viral infectious diseases is very small, which usually makes specific treatment impossible. The most important infective viruses epidemiologically, which lead to persistent complications, are discussed in detail as follows: influenza virus, measles virus, human T-cell leukaemia virus, human immuno-deficiency virus, hepatitis B and C virus. In a discussion conclusions are drawn from the virologist's point of view for a possible long-range prognosis, which depends on the one hand on the infective agent and on the other on individual reactivity. The last chapter talks about insurance medical aspects of the most important infective viruses, which have already been discussed virologically. Some scientific developments are shown which could be future solutions of problems in diagnosis and prognosis. Such new developments could help insurance medical officers to important decision parameters for long-range prognosis, which are still largely missing at present.

Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M.

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.

2'-Deoxycoformycin therapy in adult T-cell leukemia/lymphoma.

Six Caribbean patients with histologically and immunologically characterized adult T-cell leukemia/lymphoma (ATL) were treated intravenously (IV) with 2'-deoxycoformycin (DCF) at a dose of 5 mg/m2 on days 1, 2, 8, 15, and 22 with four additional weekly doses to convert any partial responses (PR) to complete responses (CR). Patients were considered eligible for this study if refractory to or relapsed from combination chemotherapy, had a life expectancy of 4 weeks or more, a performance status greater than or equal to 50%, normal renal and hepatic function, and no chemotherapy within 4 weeks. Clinical characteristics of the patients in this study included lymphadenopathy in five patients, skin involvement in four patients, bone marrow infiltration in five patients, and central nervous system involvement in two patients. Circulating ATL cells were present in four patients, and three were hypercalcemic. Of five patients evaluable for response, there was one PR of 1 month, and two minor responses lasting 2 and 3 weeks. The median duration of survival for all treated patients was 3 weeks or more. The DCF was associated with moderate side effects, including conjunctivitis in three patients, nausea and vomiting in two patients, progressive hepatic insufficiency in one patient, and moderate myelotoxicity in three patients. Infections occurred in four patients, including two cases of oral candidiasis and two cases of fatal neutropenic sepsis in patients receiving concurrent intrathecal methotrexate. As a single agent, DCF appears to have limited activity in advanced refractory/relapsed ATL. Studies in the future should explore DCF in combination with other cytotoxic agents as initial therapy in better-risk patients.

[Adult T-cell leukemia--from retrovirus-induced T-cell leukemia in dermatologic patients. Clinical histologic and epidemiologic studies]. / Adult T-cell leukemia--durch Retrovirus bedingte T-Zell-Leukämie bei dermatologischen Patienten. Klinische, histologische und epidemiologische Untersuchungen.

In 1976, adult T-cell leukemia (ATL) was reported as a special form of T-cell leukemia. In such cases the following criteria are prominent: strong inclination to leukemic change, incidence of abnormal cells in the peripheral blood, and the existence of an endemic area at the time of the outbreak of the disease. The abnormal tissue infiltrating ATL cells originate from peripheral blood T-lymphocytes, and in these lymphocytes the causal retrovirus HTLV-I could be proven. Since pathognomonic cutaneous manifestations can be observed among almost 50% of the patients, knowledge of this disease is of great importance to dermatologists. Two cases are reported focussing on the clinical and histopathologic findings concerning the cutaneous manifestations. Epidemiologically, up to 1984, we collected and analyzed 153 Japanese cases. There is a minor difference in sex distribution, but the incidence of ATL is highest among people in their fifties. The region of Kyushu, especially the southwestern part, and of Okinawa proved to be the endemic centers of ATL.

Non-Hodgkin lymphoma in Jamaica and its relation to adult T-cell leukemia-lymphoma.

Of 95 patients consecutively diagnosed with non-Hodgkin lymphoma, 52 (55%) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positivity was strongly associated with skin involvement, leukemia, and hypercalcemia (p less than 0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T-cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 9 patients had indolent courses and a median survival of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinant of adult T-cell leukemia-lymphoma.

Non-hodgkin lymphoma in Jamaica and its relation to adult T-cell leukemia-lymphoma [published erratum appears in Ann Intern Med 1987 Jun;106(6):917]

Of 95 patients consecutively diagnosed with non-hodgkin lymphoma, 52(55 percent) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positively was strongly associated with skin involvement, leukemia, and hypercalcemia (p<0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T-cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinnant of adult T-cell leukemia-lymphoma.(AU)