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Adult T‐cell leukemia/lymphoma (ATL) is a mature T‐cell neoplasm and is classified into four subtypes (acute, lymphoma, chronic, and smoldering) according to the Shimoyama classification, established in 1991 through several nationwide surveys based on the clinical diversity of patients diagnosed in 1983‐1987 in Japan. Thereafter, no such studies have been conducted. Recently, we conducted a nationwide hospital survey using the method of the 1980s studies, collected baseline data on 996 ATL patients diagnosed in 2010‐2011 from 126 hospitals, and reported their unique epidemiological characteristics. Here, we report the follow‐up results of registered ATL patients with the goal of evaluating current prognoses and treatment modalities as of 2016‐2017. Of 770 evaluable patients, 391 (50.8%) had acute‐type, 192 (24.9%) had lymphoma‐type, 106 (13.8%) had chronic‐type, and 81 (10.5%) had smoldering‐type ATL. The initial therapy regimens used for acute/lymphoma‐type ATL were vincristine, cyclophosphamide, doxorubicin and prednisone, followed by doxorubicin, ranimustine, and prednisone and then by vindesine, etoposide, carboplatin, and prednisone (VCAP‐AMP‐VECP)‐like in 38.5/41.7% and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)‐like in 14.6/13.7% of patients. Allogeneic hematopoietic stem cell transplantation was used to treat 15.9/10.4% of acute/lymphoma‐type ATL patients. The 4‐year survival rates (the median survival time, days) for acute‐, lymphoma‐, unfavorable chronic‐, favorable chronic‐, and smoldering‐type ATL were 16.8% (252), 19.6% (305), 26.6% (572), 62.1% (1937), and 59.8% (1851), respectively. The 4‐year survival rates for acute‐ and lymphoma‐type ATL improved compared with those reported in 1991, but those for chronic‐ and smoldering‐type ATL were not. Further efforts are warranted to develop more efficient therapeutic strategies to improve the prognosis of ATL in Japan. The survival curve shows that the prognoses of patients with acute and lymphoma‐type ATL in Japan have improved modestly, but those of patients with chronic and smoldering‐type ATL have not improved.

The indolent adult T-cell leukemia-lymphoma prognostic index (iATL-PI) uses soluble interleukin-2 receptor (sIL-2R) levels of 1,000 and 6,000 U/mL as a cut-off. The disadvantage of the iATL-PI is that approximately half of the patients are classified as intermediate risk (1,000 ≤ sIL-2R < 6,000). Here, we aimed to develop a novel prognostic model for indolent ATL using a prospectively registered database. We identified 375 patients with indolent ATL. Median age was 61 years. The median follow-up of surviving patients was approximately 62 months. In multivariate analysis for overall survival (OS), sIL-2R level (as log(sIL-2R), HR 4.58), male sex (HR 1.41) and LDH > ULN (HR 1.68) were independent prognostic factors. The best cut-off value for sIL-2R to predict OS was 2,870 U/mL. Including the cut-off of 3,000 U/mL in the original iATL-PI, the probabilities of 5-year OS were 88.9% in the low group (sIL-2R < 1,000), 67.5% in the low-intermediate group (1,000 ≤ sIL-2R < 3,000), 34.0% in the high-intermediate group (3,000 ≤ sIL-2R < 6,000) and 17.0% in the high group (sIL-2R ≥ 6,000). The c-index for predicting OS was higher with the modified iATL-PI than with the original iATL-PI (0.749 vs. 0.725). The addition of sex and LDH levels did not improve the c-index. In conclusion, we developed a novel prognostic index of indolent ATL.

Adult T-cell leukaemia-lymphoma (ATL) is a malignancy of peripheral T lymphocytes caused by human T-lymphotropic virus type I (HTLV-1), and its prognosis is poor. There are an estimated 5 million to 20 million HTLV-1 infected individuals worldwide; their lifetime risk of developing ATL is 3–5%, and high HTLV-1 proviral loads have been shown to be an independent risk factor. Recent advances in the treatment of ATL are the introduction of treatment targeted against CC chemokine receptor 4 (CCR4), which is abundantly expressed on most ATL cells, and allogeneic haemopoietic stem-cell transplantation for aggressive ATL. Promising outcomes are also reported with early intervention for indolent ATL with interferon α and zidovudine. Clinical trials should incorporate a validated prognostic index to assess the results, because of the difficulties associated with undertaking large-scale trials and significant diversity of clinical features with ATL, even in the same clinical subtypes (acute, lymphoma, chronic, and smoldering).

Although adult T-cell leukemia/lymphoma (ATL) has a higher burden in Latin America compared to North American or European countries, few studies have described the outcomes of this disease. We estimated the hospital-based prevalence and overall survival (OS) of ATL. We conducted a cohort study among patients aged ≥ 18 years with pathologically diagnosed mature T-cell lymphoma across 11 Latin American countries from 2000 to 2023 by pooling data from 3 hospital-based registries. We used the Kaplan-Meier method to estimate survival outcomes. Among 1963 patients with mature T-cell lymphoma, the pooled prevalence of ATL was 17 % (n = 329; 95 % confidence interval [CI]=15–18 %), with the highest observed in Peru (n = 158; 38 %, 95 % CI=33–43 %) and Colombia (n = 17; 29 %, 95 % CI=18–41 %). Over time, ATL cases only increased significantly in Peru, from 14 % in 2000–2004 to 58 % in 2019–2023 (Ptrend<0.001). With a median follow-up of 37 months (95 % CI=30–54 months), the 3-year OS of ATL was 25 % (95 % CI=20–32 %), and the median OS was 9 months (95 % CI=8–12 months). OS did not differ across countries (range 19–47 %, P = 0.210). Patients with lymphomatous ATL had worse outcomes than those with PTCL-NOS only in Peru (Pheterogeneity=0.029). Our findings indicate a higher ATL prevalence in Latin America than previously reported in North America or Europe, likely due to differences in HTLV-1 endemicity and diagnostic practices. The similar and poor survival rates across countries underscore the need for targeted interventions to improve patient outcomes. We propose expert-based research priorities and suggest further epidemiological validation studies. •ATL prevalence in Latin America is likely higher than in other regions.•Survival rates for ATL patients remain poor across countries.•Lack of HTLV screening may lead to misdiagnosis of ATL as PTCL-NOS.•Population- based validation studies and expert-based research priorities and are needed to improve outcomes•Collaborative capacity-building will accelerate discovery and enhance ATL-related health outcomes globally

Genetic alterations in adult T‐cell leukemia/lymphoma (ATLL), a T‐cell malignancy associated with HTLV‐1, and their clinical impacts, especially from the perspective of viral strains, are not fully elucidated. We employed targeted next‐generation sequencing and single nucleotide polymorphism array for 89 patients with ATLL in Okinawa, the southernmost islands in Japan, where the frequency of HTLV‐1 tax subgroup‐A (HTLV‐1‐taxA) is notably higher than that in mainland Japan, where most ATLL cases have HTLV‐1‐taxB, and compared the results with previously reported genomic landscapes of ATLL in mainland Japan and the USA. Okinawan patients exhibited similar mutation profiles to mainland Japanese patients, with frequent alterations in TCR/NF‐ĸB (eg, PRKCB, PLCG1, and CARD11) and T‐cell trafficking pathways (CCR4 and CCR7), in contrast with North American patients who exhibited a predominance of epigenome‐associated gene mutations. Some mutations, especially GATA3 and RHOA, were detected more frequently in Okinawan patients than in mainland Japanese patients. Compared to HTLV‐1‐taxB, HTLV‐1‐taxA was significantly dominant in Okinawan patients with these mutations (GATA3, 34.1% vs 14.6%, P = .044; RHOA, 24.4% vs 6.3%, P = .032), suggesting the contribution of viral strains to these mutation frequencies. From a clinical viewpoint, we identified a significant negative impact of biallelic inactivation of PRDM1 (P = .027) in addition to the previously reported PRKCB mutations, indicating the importance of integrated genetic analysis. This study suggests that heterogeneous genetic abnormalities in ATLL depend on the viral strain as well as on the ethnic background. This warrants the need to develop therapeutic interventions considering regional characteristics. Targeted next‐generation sequencing and single nucleotide polymorphism array were applied to analyze aggressive adult T‐cell leukemia/lymphoma in Okinawa, which were not included in prior genomic studies. Our results showed that HTLV‐1 tax subgroup‐A was associated with high alteration frequencies in GATA3 and RHOA. Clinically, biallelic alterations, not heterozygous deletions or mutations, of PRDM1 were significantly associated with poor prognosis.

T lymphoblastic leukemia /lymphoma (T-ALL/LBL) is a rare and highly aggressive neoplasm of lymphoblasts. We evaluated 195 T-ALL/LBL adolescent and adult patients who received ALL-type chemotherapy alone (chemo,n = 72) or in combination with autologous hematopoietic stem cell transplantation(auto-HSCT,n = 23) or allogeneic hematopoietic stem cell transplantation(allo-HSCT,n = 100) from January 2006 to September 2020 in three Chinese medical centers. 167 (85.6%) patients achieved overall response (ORR) with 138 complete response (CR) patients (70.8%) and 29 partial response (PR) patients (14.8%). Until October 1, 2023, no difference was found in 5-year overall survival (5-OS) and 5-year progression free survival(5-PFS) between allo-HSCT and auto-HSCT (5-OS 57.9% vs. 36.7%, P = 0.139, 5-year PFS 49.4% vs. 28.6%, P = 0.078) for patients who achieved CR, for patients who achieved PR, allo-HSCT recipients had higher 5-OS compared with chemo alone recipients (5-OS 23.8% vs. 0, P = 0.042). For patients undergoing allo-HSCT, minimal residual disease (MRD) negative population showed better 5-OS survival compared with MRD positive patients (67.8% vs. 19.6%, p = 0.000). There were no significant differences between early T-cell precursor (ETP), NON-ETP patients with or without expression of one or more myeloid-associated or stem cell-associated (M/S+) markers (NON-ETP with M/S+, NON-ETP without M/S+) groups in allo-HSCT population for 5-OS. (62.9% vs. 54.5% vs.48.4%, P > 0.05). Notch mutations were more common in patients with non-relapsed/refractory disease than relapsed/refractory disease (χ² =4.293, P = 0.038). In conclusion, Allo-HSCT could be an effective consolidation therapy not just for patients with CR, but also for those who achieved PR. The prognosis is significantly improved by obtaining MRD negative prior to allogeneic transplantation.

The prognosis of adult T-cell leukemia/lymphoma (ATL) with primary central nervous system (CNS) involvement has been unclear since the advent of new therapies. Recently, we have shown that flow cytometric CD7/CADM1 analysis of CD4 + cells (HAS-Flow) is useful to detect ATL cells that are not morphologically diagnosed as ATL cells. We investigated the role of CNS involvement in ATL using cytology and HAS-Flow by analyzing cerebrospinal fluid (CSF) from 73 aggressive ATL cases. Based on the findings in CSF, the study subjects were classified into CNS + (cytologically malignant, n  = 18), CNS- (cytologically non-malignant and ATL cell population negative in HAS-Flow, n  = 44), and CNS-Micro (cytologically non-malignant and ATL cell population positive in HAS-Flow, n  = 11) groups. As expected, the CNS + group had a shorter overall survival than the CNS- groups ( P  < 0.001). However, the CNS-Micro group showed no adverse impact on overall survival compared to the CNS- group ( P  = 0.506), even without additional CNS-targeted treatments. HAS-Flow also demonstrated clinical utility in the diagnosis of CSF lesions in ATL patients with cerebral white matter lesions and in the detection of ATL cells on post-treatment CSF examination in patients with CNS involvement. Our study demonstrates that ATL with CNS involvement have a poor prognosis and that CSF HAS-Flow is useful to assist in the diagnosis of suspected CNS involvement and to detect ATL cells with high sensitivity after treatment.

Recent advances in treatment for adult T‐cell leukemia‐lymphoma (ATL) are reviewed herein. It is currently possible to select a therapeutic strategy for ATL and predict prognosis by classification of patients by clinical subtypes and clinicopathological factors. Although the overall survival (OS) of patients with ATL has increased marginally because of advances in chemotherapy, further prolongation of survival might be difficult with conventional chemotherapy alone. Promising results have been reported for antiviral therapy using zidovudine and interferon‐α, and, indeed, antiviral therapy is currently the standard treatment for patients with ATL in western countries. Remarkably, the 5‐year OS rates are 100% for both the smoldering‐type and chronic‐type ATL. Recently, treatments for ATL have included allogeneic hematopoietic stem cell transplantation and molecular targeted therapies. Furthermore, the anti‐CCR4 monoclonal antibody mogamulizumab has been shown to have marked cytotoxic effects on ATL cells, especially in the leukemic type of ATL. In the lymphoma type of ATL, the response rate may be improved by combining mogamulizumab with chemotherapy. It should be recognized that prevention of infection from carriers of human T‐cell leukemia virus type‐I and transfer of the virus from mother to infant are crucial issues for the eradication of ATL. The prognosis of ATL is very poor by conventional chemotherapies. On the other hands, antiviral therapy of zidovudine and interferon‐α is currently the gold standard for patients with leukemic type ATL in Western countries although it is not confirmed yet in Japan. By various attempts including allogeneic hematopoietic stem cell transplantation and molecular target therapies, around one‐third of aggressive type ATL cases can be now cured.

Adult T-cell Leukemia/Lymphoma (ATL) is caused by human T-leukemia virus type 1 (HTLV-1). Over 10 million people are infected worldwide, but only up to 5% develop ATL. HTLV-1 infection is endemic in Peru; however, there are currently no reports focusing on the epidemiological characteristics of Peruvian individuals with ATL. Data from the HTLV-1 Unit registry covering the period from June 1992 to November 2023 were retrospectively analyzed. Clinical report forms and histopathology records from national referral cancer centers were reviewed. Descriptive statistics were used to characterize patients, and Kaplan-Meier methods assessed survival by ATL subtype. A total of 116 confirmed ATL cases were identified. There was a slight female predominance, with 52.6% women (n = 61) and 47.4% men (n = 55). The median age at diagnosis was 54 years (IQR 42-61), with 42.2% of patients diagnosed before age 50. Only 13.8% of patients (n = 16) were diagnosed with HTLV-1 infection before ATL development, and only 8 of those were diagnosed through routine screening. The most common ATL subtype was lymphomatous (65.5%), followed by smoldering/chronic (24.1%), and acute ATL (9.5%). With a median follow-up of 15.9 months, median survival times were 6.5, 12.5, and 89.6 months for acute, lymphomatous, and smoldering/chronic subtypes, respectively. One-year survival rates ranged from 37.5% in acute ATL to 84.6% in smoldering/chronic ATL. Comorbid HTLV-1-associated diseases included infective dermatitis (15.5%), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) (8.6%), and Strongyloides stercoralis hyperinfection (6.9%). This is the first study to describe ATL epidemiology in Peru from an infectious disease perspective. Most patients were unaware of their HTLV-1 status before developing ATL, highlighting missed opportunities for earlier detection. Routine HTLV-1 testing should be considered in the evaluation of T-cell malignancies in endemic countries. In addition, screening high-risk populations could support earlier diagnosis and reduce transmission. Improving access to diagnostic tools, along with stronger collaboration between infectious diseases and oncology services could improve patient outcomes in endemic regions.

Adult T‐cell leukemia/lymphoma (ATLL) is a mature T‐cell neoplasm, and is divided into 2 indolent (smoldering and chronic) and 2 aggressive (acute and lymphoma) clinical subtypes. Based on previous integrated molecular analyses suggesting the importance of the JAK‐STAT pathway in ATLL, we attempted to clarify the clinicopathological significance of this pathway. Clinical and morphological findings were reviewed in 116 cases with ATLL. The nuclear localizations of phosphorylated STAT3 (pSTAT3), pSTAT5, and pSTAT6 were analyzed by immunohistochemistry. Targeted sequencing was undertaken on the portion of STAT3 encoding the Src homology 2 domain. Expression of pSTAT3 was observed in 43% (50/116) of ATLL cases, whereas pSTAT5 and pSTAT6 were largely undetected. Cases with the lymphoma type showed significantly less frequent pSTAT3 expression (8/45, 18%) than those with the other subtypes (41/66, 62%; P < .001). STAT3 mutations were detected in 36% (10/28) and 19% (12/64) of cases with the smoldering and aggressive types of ATLL, respectively. The correlation between STAT3 mutation and pSTAT3 expression was not significant (P = .07). Both univariate and multivariate analysis revealed that pSTAT3 expression was significantly associated with better overall survival and progression‐free survival in the smoldering type of ATLL, whereas STAT3 mutation was not related to a line of clinical outcome. Collectively, our data show that only the lymphoma type showed a low prevalence of tumor cells positive for pSTAT3 expression, and raises the possibility that pSTAT3 expression is a novel biomarker to predict better prognosis in the smoldering type of ATLL. In the present study, we investigated the potential role of the STAT3 pathway in adult T‐cell leukemia/lymphoma (ATLL). We carried out immunohistochemistry for activated/phosphorylated STAT3 (pSTAT3) and compared with STAT3 mutation and clinical subtypes of ATLL. We found that the expression of pSTAT3 is detected in ATLL cells except for the lymphoma type, and that the prevalence of cells positive for pSTAT3 correlates with favorable overall and progression‐free survival exclusively in the smoldering type. In contrast, mutation of STAT3 was not significantly correlated with clinicopathological findings in ATLL.