Analysis of Large Cohort Shows That Caribbean Adult T Cell Leukemia/Lymphoma Is a Chemotherapy Refractory Disease with Very Poor Prognosis That Behaves Distinctly from Japanese Subtypes
Authors: Zell Monica I , Assal Amer , Konda Bhavana , Braunschweig Ira , Derman Olga , Kornblum Noah , Battini Ramakrishna , Verma Amit , Janakiram Murali 
Published: October 2019

Abstract
Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a rare mature T-cell malignancy associated with human T-lymphotropic virus type 1 (HTLV-1) infection that is endemic in Japan, Western Africa and the Caribbean. Most studies focus on Japanese ATLL and little is known about the presentation and outcomes in the Caribbean population. We conducted a retrospective analysis of clinicopathologic features, treatment patterns and disease outcomes of ATLL in a large, predominantly Caribbean cohort in the Bronx.
Methods: Patient records were queried using a data mining software to identify all cases of HTLV positivity and ATLL. The diagnosis of ATLL was confirmed based on clinical history, pathological findings and HTLV-1 positivity. We used the Shimoyama criteria to confirm ATLL subtypes. A minority of patients in our cohort presented with chronic disease (n=2), so this analysis focuses on acute and lymphomatous cases. Date of discharge to palliative care was equated to date of death when it was not available (n=10) and a clear documentation of refractory progressive disease was confirmed.
Results: We identified 51 cases of ATLL at Montefiore Medical Center- Albert Einstein College of Medicine between 2003 and 2014, and present 43 patients (31 acute, 12 lymphomatous) who were diagnosed and treated at our institution. Median age at presentation was 54 (range 28-87), with most patients (67%) younger than 60 years. Female predominance was noted (63%) which differs from the Japanese literature. All patients were of Caribbean origin (96%) except one each from Ghana and Honduras. Of tested patients (67%), none were positive for HIV. The majority of patients had the classic CD4+/CD8- ATLL immunophenotype (90%), while fewer had an atypical phenotype (CD4+/CD8+ (6%) or CD4-/CD8- (4%)).
Patients presented with generalized lymphadenopathy (82%), bone marrow involvement (79%), hepatosplenomegaly (56%), skin involvement (33%), lung involvement (23%), lytic lesions (21%) or central nervous system (CNS) involvement (38%). Lab abnormalities included hypercalcemia (64%), leukocytosis (61%) and an LDH above 200 in all patients. Features of higher risk disease (hypercalcemia, high LDH, bone marrow and CNS involvement) are more prevalent in this cohort than previously reported in Japanese cohorts.
Clonal T-cell receptor gene rearrangements were present in all patients. In the 10 patients who underwent cytogenetic testing, multiple cytogenetic abnormalities were present including aneuploidy of ATLL hot spot 14q32 in 50% of patients. Other loci of abnormalities found in two or more patients included: 11q23, 11q13, 9p13, 19p13, 3q21, 20q11, and 14q10, some of which (11q, 19p, and 20q) have not been previously described.
Overall 79% of patients received first-line treatment, while 21% were not treated due to poor performance status and other comorbidities. Chemotherapy alone was administered in 53% of patients (45% acute, 67% lymphomatous), chemotherapy with concurrent antiretroviral therapy in 41% (50% acute, 25% lymphomatous), and antiretroviral therapy alone in 4% (5% acute, 8% lymphomatous) of patients. First-line chemotherapy regimens included CHOP (25%), EPOCH (66%), and hyper CVAD (13%). Antiretroviral therapy included nucleoside analogs (64%) and integrase inhibitors (36%). Complete response rate for first-line therapy was 21%. Strikingly, only one patient was cured after first-line therapy. Median overall survival (OS) was 5.5 months. For patients who received first-line therapy, median OS was 7 months compared to 0.5 months in patients who did not. One hundred day mortality was 35% from the date of diagnosis. Matched donors were scarce for this population. Only 5 patients underwent allogeneic HSCT as matched donors were difficult to find; 2 died from acute GVHD, 1 was recently transplanted in the past 100 days and is in complete remission and 2 patients are alive for greater than 12 months.
Conclusion: We present the largest descriptive case series of ATLL in the Caribbean population and show that it is a distinct disease entity when compared to Japanese cohorts. Caribbean ATLL has a worse prognosis, presents predominantly in acute and lymphomatous stages and has a high rate of primary refractory or relapsed disease after chemotherapy. These data suggest that allogeneic HSCT should be considered early in this population and reinforces the acute need for novel treatments for this disease.

Disclosures
No relevant conflicts of interest to declare.