Real-World Data on Adult T-Cell Leukemia/Lymphoma in Latin America: A Study From the Grupo de Estudio Latinoamericano de Linfoproliferativos

Abstract

PURPOSE Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking. PATIENTS AND METHODS We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test. RESULTS We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year survival rates of 8%, 22%, 40%, and 80%, respectively. First-line zidovudine (AZT)-interferon alfa (IFN) resulted in an overall response rate of 63% (complete response [CR] 24%) for acute. First-line chemotherapy yielded an overall response rate of 41% (CR 29%) for lymphomatous. CR rate was 42% for etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone versus 12% for cyclophosphamide, vincristine, doxorubicin, and prednisone–like regimen ( P < .001). Progression-free survival at 1 year for acute type patients treated with AZT-IFN was 67%, whereas 2-year progression-free survival in lymphomatous type patients who achieved CR after chemotherapy was 77%. CONCLUSION This study confirms Latin American ATLL presents at a younger age and has a high incidence of lymphomatous type, low incidence of indolent subtypes, and worse survival rates as compared with Japanese patients. In aggressive ATLL, chemotherapy remains the preferred choice for lymphomatous favoring etoposide-based regimen (etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone), whereas AZT-IFN remains a good first-line option for acute subtype.

Epidemiology of Adult T-Cell Leukaemia/Lymphoma in South Africa over a 10-Year Period

“…In this study, ATLL was seen equally in male and female patients, as is seen across many geographical regions [ 5 , 7 , 8 , 18 ]. The median age at diagnosis of ATLL is 37 years in South Africa, much lower than the 6 th decade of life seen in Japan, the 5 th decade in the USA and Latin America, and still lower than the median age of 44 years seen in a Brazilian study [ 4 – 8 ].…”

“…In this study, acute ATLL was the most common subtype of ATLL accounting for 84% of the ATLL cases. There was only one patient with lymphomatous ATLL in South Africa over the 10-year period, despite lymphomatous ATLL being relatively common in other geographic regions [ 4 – 7 ]. While in Japan, acute ATLL is also most commonly seen, accounting for approximately half of their ATLL cases, lymphomatous ATLL is the second most common seen in approximately a quarter of ATLL cases [ 4 , 5 ].…”

“…The acute subtype is the most common subtype of ATLL in Japan, seen in 49.5% to 56.1% of patients ( n = 922, collected over a 2-year period, and n = 1594, collected over 9-year period, respectively) [ 4 , 5 ]. In contrast, the lymphomatous subtype is the most common subtype in the USA (49.2%, n = 195, collected over a 30-year period) and Latin America (50.2%, n = 253, collected over a 25-year period) [ 6 , 7 ]. In Japan, the median age at diagnosis is 61 to 70 years across the different subtypes of ATLL [ 4 , 5 ].…”

ETS1 is a novel transcriptional regulator of adult T-cell leukemia/lymphoma of North American descent

“…There is evidence that ATLL in South America, where Cosmopolitan subtype 1a subgroup A is dominant, has more aggressive clinical course and younger age of diagnosis compared to J-ATLL, although subtype distribution may favor lymphomatous rather than acute as observed in NA-ATLL. 62 Of particular interest will be characterization of ATLL in patients of Melanesian descent with the more divergent HTLV-1c genotype as well as patients of African descent where HTLV-1b and a spectrum of HTLV-1a subgroups are endemic. 63 It has been suggested that HTLV-1c may be less oncogenic than Cosmopolitan subtype 1a, but likely underreporting as well as differences in life expectancy and environmental factors, particularly in indigenous populations, have made this comparison difficult.…”

Decline in human T‐cell lymphotropic virus seroprevalence in blood donors from Minas Gerais, Brazil over a 12‐year period (2006–2017)

“…Human T‐cell lymphotropic virus (HTLV) is a human retrovirus classified into four types with specific geographical occurrence: Types 1 and 2 (HTLV‐1 and HTLV‐2) are distributed worldwide, 1,2 whereas Types 3 and 4 are limited to Central African regions 3 . HTLV‐1 is known to be the causative agent of diseases, such as adult T‐cell leukemia/lymphoma (ATL), a malignant T CD4+ cell proliferation disease, HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive neurodegenerative disease, and other several systemic inflammatory disturbances 4–9 . Although HTLV‐1‐associated disease has a low prevalence in the carriers (2%–8%), it can lead to death or cause severe disability that impacts the quality of life of affected individuals 10–12 .…”