Epidemiology of Adult T-Cell Leukemia/Lymphoma in Martinique (1983-2013): Robustness of Classification of Lymphoma Study Group of Japa, Relevance of Cutaneous Lesions, Atypical Phenotype and Origin of the HTLV-1 Infected Cell

We describe the epidemiological, clinical and biological features of the patients with ATL (Acute T-cell Leukaemia), extracted from the Hematological Cancer Registry of Martinique, between January 1st, 1983 and March 31st, 2013 and confront our experience with the acquired data.One hundred and seventy-five new cases of ATL were listed. All the patients with ATL were of mixed African-Caucasian descent. There were 88 men and 87 women. The median age was 56 years (from 16 to 95). One hundred and forty six patients (83,4 %) were more than 40 years old. According to the classification of the Lymphoma Study Group of Japan ( LSG) (Shimoyama M and al, Br J Haematol on 1991), the distribution of the 3 clinical types, acute, lymphoma and chronic, was respectively 62.9 % (N=110), 29.1 % (N=51) and 8 % (N=14). None smoldering type was identified. Three cases presented exclusive skin lesions. The median survival time was 5,43 months for all the cases, 3.09 months for the acute type, 8.13 for the lymphoma type and 45.16 for the chronic type (fig 1, p value of log-rank test < 0.001). The survival was significantly higher for the lymphoma type with skin lesions (fig 2, median: 13.96 versus 6.06 months, p value of log-rank test < 0.035) and for the acute type without hypercalcemia (4 versus 2.4 months, p< 0.01). The symptoms associated with hypercalcaemia present in 82 patients (47 %) and skin lesions present in 74 patients(42 %) were the most successful clinical signs for the diagnosis of ATL. Forty two percent were infected by Strongyloïdes stercoralis (Ss). Over the studied period, 154 patients (104 acute, 41 lymphoma, 9 chronic) died with a median overall survival of 4.68 months, 6.22 for the lymphoma type and 2.86 months for the acute type. The hypercalcemia was the first cause of death. No strict lymphoma type (atypical lymphoïd cells < 1%) progressed to a leukaemia form. In most of the cases, the ATL cell presented the activated post-thymic T cell phenotype CD2, CD3, CD4, CD25. Weak expression of CD3 and TCR was observed in every case analyzed. The absence of CD7 membrane expression was observed in 75 among 96 cases. This typical phenotype applied to 79,6 % of the leukaemia patients. Twenty three patients had a different phenotype: double negative ( DN) CD4(-) CD8(-)( 14 cases), double positive ( DP) CD4(+)CD8(+) (4 cases) and negative CD3(-) (4 cases) and CD8(-) (1 case). Five DN cells expressed CD7. The patients with an atypical phenotype had a significantly lower survival (median: 2.0 versus 5.76 months, p=0.013). In our series, the epidemiological and clinical characteristics of patients with ATL were comparable with those of the series of Japan and Jamaica. Scarcity of evolution from a type to another testified to the robustness of the LSG and suggested that the natural history of the tumoral cells of the various types of ATL was different. Hypercalcaemia was a discrimination factor for severity, particularly in the acute type, and the major cause of death. Skin lesions conferring a better prognosis, in particular in the lymphoma type, required early detection of these lesions in indolent disease and in HTLV-1 healthy carriers, especially among relatives of patients with ATL and/or infected by Ss, and suggested that their treatment could limit transformation to the aggressive forms of ATL. The atypical phenotypes, in particular DN cases, CD7 (- ) or CD7 (+), DP cases and CD3(-) cases, could be interpreted as thymic progenitors. Also, weak expression of the complex CD3 / TCR observed on ATL cells suggested that the target cell had acquired an intermediate differentiation level between immature cortical thymocytes and mature thymocytes. The scarcity of ATL in adolescents, associated with the strong majority of the patients being more than 40 years old, suggested the hypothesis of the necessity of the "involution" of the thymus for an accomplished ATL cell.