Characterization of patients with aggressive adult T-cell leukemia-lymphoma in Okinawa, Japan: a retrospective analysis of a large cohort.

Okinawa Prefecture, located in the subtropics, is an area of endemic adult T-cell leukemia-lymphoma (ATL) in Japan. We retrospectively analyzed 659 patients with aggressive ATL in seven institutions in Okinawa between 2002 and 2011. The median patient age was 68 years. More patients were aged ≥90 years (2.6 %), in this study, than in a nationwide survey (<1 %). The median survival time (MST) of the entire cohort was 6.5 months. Of the 217 patients who had a clinical status similar to that stated in the eligibility criteria of JCOG9801 (a randomized phase III study comparing VCAP-AMP-VECP with CHOP-14), 147 who received the CHOP regimen had a poorer MST than those in the CHOP-14 arm of JCOG9801 (8 vs 11 months). The prevalence of strongyloidiasis in the ATL patients was much higher (12.4 %) than in the historical cohort who visited the University of the Ryukyus Hospital (3.4 %). Furthermore, strongyloidiasis may be associated with ATL-related deaths. These findings suggest that, compared with other areas in Japan, in Okinawa, the proportion of patients aged ≥90 years with clinical features of aggressive ATL is higher, outcomes are poorer, and the disease is associated with a higher prevalence of strongyloidiasis.

Adult T-cell leukaemia/lymphoma-like human T-cell leukaemia virus-1 replication in infective dermatitis.

Adult T-cell leukaemia/lymphoma (ATLL) is a malignant T-cell proliferation that occurs in 3-5% of individuals infected with human T-cell leukaemia virus-1 (HTLV-1). HTLV-1 infection is also linked to the development of infective dermatitis (ID), an exudative dermatitis of children that has been proposed as a cofactor of ATLL. Here, HTLV-1 replication was investigated over time in a girl with ID and multiparasitic infestation including strongyloidiasis, a disease also known to predispose HTLV-1 carriers to ATLL. Quantitative polymerase chain reaction (PCR) revealed extremely high proviral loads. During the 2-year period of the present study, the proportion of circulating infected cells ranged between 12% and 36%. Quadruplicate linker-mediated PCR amplification of HTLV-1 flanking sequences identified a pattern of extensive and persistent oligoclonal expansion of infected lymphocytes. As viral loads, both the number and the degree of infected T-cell expansion were independent of treatment or clinical signs. However, the temporal fluctuation of proviral loads correlated significantly with the degree of infected T-cell expansion, but not with the overall number of detected clones. This pattern of HTLV-1 replication over time is very different from that observed in asymptomatic carriers and reminiscent of that observed in ATLL, a result consistent with the proposal of ID as an ATLL cofactor.

Effect of Strongyloides stercoralis infection and eosinophilia on age at onset and prognosis of adult T-cell leukemia.

Onset of adult T-cell leukemia (ATL) usually follows a long period of viral latency. Strongyloides stercoralis infection has been considered a cofactor of leukemogenesis. Hypereosinophilia (HE) is also observed and could be associated with either the presence of parasites or the leukemic process. In non-Hodgkin's lymphoma, eosinophilia may or may not affect prognosis. To determine whether infection with S stercoralis and therefore eosinophilia has a significant effect on the development of ATL, we studied two variables in 38 patients: age at onset and median survival rate. Infected (Ss+) patients (n = 19) were younger (P = .0002) and survived longer (P = .0006) than uninfected (Ss-) patients (n = 19) (median age, 39 vs 70 years; median survival, 167 vs 30 days). Mean survival of patients with hypereosinophilia (HE+) was not significantly different from that of patients without hypereosinophilia (HE-) (P = .57). However, overall survival was longer for Ss + HE + patients than for Ss-HE-patients (P = .01; 180 vs 30 days) or Ss-HE + patients (P = .03; 180 vs 45 days). Among patients with mean survival more than 180 days, Ss + HE + patients survived longer (P = .028). Our data confirm that cofactors related to the environment, such as S stercoralis and hypereosinophilia associated with S stercoralis or human T-cell leukemia virus, type 1 (HTLV-1) might be important in HTLV-1-associated leukemogenesis and suggest that hypereosinophilia affects the prognosis of HTLV-1-associated leukemia.