Outcome of an Urban Cohort of North American Adult T-Cell Leukemia/Lymphoma Patients
Authors: Qureshi Haris , Kiwan Ahmad , Foss Francine M. , Kothari Shalin , Huntington Scott F , Isufi Iris , Seropian Stuart , Sethi Tarsheen 
Published: December 2024

Background:
Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive malignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection which is endemic in Japan, the Caribbean, Central Africa, and parts of South America. North American ATLL has distinct clinical and biologic characteristics than Asian ATLL, including differential response to treatment. This study was designed to evaluate the unique characteristics , treatment response, survival outcome and role of allogeneic stem cell transplant (alloSCT) in ATLL in an urban North American cohort.
Methods: We used the Yale Joint Data Analytics Team (JDAT) to identify patients(pts) with ATLL diagnosed between 2002 and 2023. Key data including clinicopathologic characteristics, treatment and survival were collected from the electronic health records. Survival data was analyzed using the Kaplan-Meier Method with log-rank test and Cox proportional hazards regressions for univariate and multivariable analyses. A P value of &lt;0.05 was considered significant. Statistical analysis was performed using STATA 14.2 software.
Results:
Twenty-three patients were included in analysis. Median age of diagnosis was 56 years (25-88) with 15 females (65%) and 8 males (35%). Majority of patients (87%) were of Caribbean origin with 78% identifying as Black or African American and 13% as Hispanic. Thirteen (57%) presented with acute subtype, 6 (26%) with smoldering disease, and 4 (17%) with lymphomatous subtype. At diagnosis, the median white blood cell (WBC) count was 9.4 ( range 3-112.2) and LDH was 417.5 (175-3663). Most patients (96%) presented with lymphadenopathy, 22% had splenomegaly, 4% had hepatomegaly, 17% had pulmonary disease, 13% had cutaneous manifestations, and 13% had other extranodal disease. At diagnosis, 9% had latent TB , one had human immunodeficiency virus (HIV), and one had candidiasis. Bone marrow was positive in 53% and 21 of 22 had circulating leukemia cells. FISH and karyotype were available in 10 pts and showed multiple chromosomal abnormalities in 9 and p53 mutation in 1. Of these 10 pts, only 2 are alive.
First line treatments included EPOCH 39% (9), CHOEP (4), AZT/interferon (IFN) (3), CHOEP/EPOCH (2), AZT/IFN /EPOCH (1), HyperCVAD (1), high-dose methotrexate (HD-MTX) (1), and CHOP (1). Ten (45%) patients received CNS prophylaxis including intrathecal (IT)-MTX 50%, HD-MTX 30%, and IT-cytarabine 20%. The intent was to transplant all eligible patients with a complete response (CR) or a good partial response (PR). Response to first line therapy included CR in 6, PR in 10 and progressive disease (PD) in 7. Patients attaining CR or PR who were eligible for alloSCT based on donor availability and comorbidity score, received bridging therapy with several cycles of brentuximab (if CD30+) or nelarabine. The 8 pts who were able to undergo alloSCT had a median age of 45 years (25-65). Six pts had haploidentical matched donors, 1 had matched related donor and 1 had a matched unrelated donor.
At a median follow-up of 58 months (mo), the median progression free survival (PFS) to first line treatment for the cohort of 23 pts was 8.6 mo (95%CI-4.6-13) and median overall survival (OS) was 23.4 mo (95%CI-8-33). For the alloSCT cohort, the median OS was 33 mo (95%CI 15 to NR) vs 13 mo (95%CI 2-26) for non-SCT group [HR0.39; P=0.08]. Five patients relapsed after alloSCT; the median time to relapse was 6.3 mo (95%CI-13 to 7). Of 5 pts who died after alloSCT, the median survival after transplant was 11.4 mo (95%CI 3 to 16) and most common cause of death was PD. In multivariable analysis for OS using three covariates of age at diagnosis, WBC count at diagnosis and alloSCT , age (HR 1.09; p= 0.008 ; 95% CI 1.02 to 1.16) and WBC at diagnosis (HR 1.03; p= 0.010 ; 95% CI 1.01 to 1.06) were associated with a worse OS.
Conclusions: In this single institution cohort of ATLL patients, we report that despite aggressive front line multi-agent chemotherapy, only a third of patients were able to undergo potentially curative alloSCT. The novel use of agents such as brentuximab and nelarabine improved disease status at the time of transplant, however, outcomes remain poor with most progressing in the front line. Within the limitations of a single institution cohort, we report that age and WBC count at diagnosis are associated with a worse OS. Accurate diagnosis and early referral to centers with transplant and clinical trial availability is key to management of ATLL patients.