OUTCOMES OF PATIENTS WITH ADULT T-CELL LEUKEMIA/ LYMPHOMA (ATLL) IN A UNIVERSITY AND PUBLIC CANCER CENTER IN BRAZIL

Abstract

Introduction: Adult T-cell Leukemia/Lymphoma (ATLL) is a hematological malignancy caused by the Human T-cell lymphotropic virus type 1 (HTLV-1). ATLL has a broad clinical presentation, with a poor prognosis and limited therapeutic options. In 2012, the prevalence of HTLV-1 infection in Brazil was estimated at 83 to 222 cases per 100,000 blood donors, with 800,000 people expected to be living with the virus. Despite being an endemic country for the virus, the number of registered cases of ATLL is much lower than would be expected, indicating an underdiagnosed and poorly characterized disease in Brazil. Methods: This is a retrospective observational study conducted at HC-FMUSP. Our hospital has an outpatient clinic for the monitoring of asymptomatic HTLV-1 carriers, with 720 patients followed since 1994. We describe the analysis of clinical, laboratory and epidemiological data collected from the medical records of patients diagnosed with ATLL from 1994 to 2022. Results: Overall, 55 patients were included and classified according to Shimoyama's classification groups. Median age at diagnosis was 52 years. Twenty nine patients (52%) were diagnosed with indolent (smoldering/chronic), 7 (13%) with lymphoma, and 18 (35%) with acute ATLL. Most patients diagnosed with indolent forms (22 out of 29) came from the cohort of asymptomatic HTLV-1 carriers. Most patients (51%) only discovered HTLV-1 infection at the time of ATLL diagnosis, this being particularly higher (76%) among patients diagnosed with an aggressive clinical form. For those patients followed at the outclinic, the median time between the diagnosis of HTLV-1 infection and the diagnosis of ATLL was 9 years (IQR 2-17). Fourteen patients with the smoldering/chronic disease evolved to an aggressive ATLL form, with a median time to progression of 2 years (IQR 0.8-3.8). These patients had a median overall survival of just 55 days after the diagnosis of the aggressive form. The median overall survival was 11 years for smoldering, 3.4 for chronic, 0.9 years for lymphomatous and 1.1 years for acute forms. A total of 35 patients received chemotherapy for aggressive disease, showing a low rate of response (20%), with CHOEP being the most commonly used protocol. Only 4 patients underwent allogeneic bone marrow transplantation, and one of them has the longest survival at the follow-up, at 7 years. Discussion: Having one of the largest HTLV-1 carrier populations worldwide, Brazil still needs better monitoring and characterization of ATLL. Even in a reference center where asymptomatic HTLV-1 infection is monitored, half of the cases were diagnosed already in an aggressive clinical form, with many patients only discovering HTLV-1 infection at the time of ATLL diagnosis. Patients who progressed from indolent forms of disease during follow-up had a very poor prognosis, similar to those initially diagnosed with aggressive forms, which is measured in months. Few patients are eligible for allogeneic bone marrow transplantation, the only curative therapy for the disease. Conclusion: Our findings highlight the underdiagnosis of HTLV-1 infection in Brazil and the lack of effective measures to prevent disease progression and treat aggressive disease forms. This emphasizes the importance of screening and preventive measures for viral transmission in our country.