Treatment Outcomes in Relapsed/Refractory Adult T-Cell Lymphoma/Leukemia and Role of CNS Prophylaxis: A New York City Hospital Experience
Authors: Mukhi Nikhil , Verma Vaibhav , Ahmed Anam , Lim Hana , Gonsky Jason , Sidhu Gurinder 
Published: November 2019

Abstract
Background:
Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive peripheral T-cell neoplasm characterized by clonal human T-cell lymphotropic virus type-1 (HTLV-1) proviral DNA integration with host T lymphocytes.It presents as aggressive (acute/lymphomatous) or indolent (chronic/smouldering) subtypes. The aggressive subtypes have median survival of 6-13 months despite aggressive chemotherapy regimens. Presently, there is no established therapy for patients with relapsed/refractory disease. The data on efficacy of traditional chemotherapy agents in this setting is scant. In the last 6 years, 4 new drugs have been approved by US Food and Drug Administration for patients with relapsed/refractory peripheral T cell lymphoma (PTCL): pralatrexate and 3 histone deacetylase (HDAC) inhibitors (romidepsin, belinostat, vorinostat). Treatment approaches for PTCL are often applied to ATLL, as there is little data available for this subtype. However, none of the HDAC inhibitor trials included ATLL patients and there was only one patient in the pivotal PROPEL study for pralatrexate. The prevalence of CNS disease in the aggressive subtypes varies from 3 to 50 % and the efficacy of intrathecal chemotherapy is not known.
Methods:
To investigate the therapeutic benefit of second-line therapy and prophylactic intrathecal therapy, we reviewed all patients with ATLL at King's County Hospital between 2006 and 2014. Individual chart review was performed to report clinicopathologic features and treatment outcomes. SPSS was used for statistical analysis.
Results:
Fifty five patients were identified between January 2006 and December 2013 including 33 (60%) females and 22 (40.0%) males with a median age of 54 years (range, 31-78 years). All patients had immigrated to the United States from the Caribbean or South America. Median follow-up period was 6.6 months (0.4-124). Forty four patients were dead, 5 were alive and 6 were lost to follow-up at the time of analysis. Stage distribution was 26%, 51%, 16%, 6% for stage I, II, III and IV respectively. Forty three patients (78.2%) received etoposide/prednisone/vincristine/cisplatin/adriamycin (EPOCH) for first-line therapy. Twenty nine patients received second-line chemotherapy: gemcitabine/oxaliplatin, iphosphamide/cisplatin/etoposide (ICE), romidepsin, pralatrexate and high dose methotrexate. Median progression free survival was 6.8 weeks (range 1.6-72). No complete responses were seen. Partial response was seen in 9 (n=29) patients (31%). Median duration of response was 20.8 weeks (range 9.1-40). Three (5%) patients had CNS involvement at presentation. Prophylactic intrathecal therapy with methotrexate (IT MTx) 12 mg Q14 days was given to 21 patients (40.3%). CNS relapse was seen in 3 (14.2%) patients who received IT MTx and 6 (19.4%) patients who did not receive intrathecal chemotherapy. All patients with CNS relapse also had peripheral relapse.
Conclusion:
ATLL is a rare and difficult disease to manage. In our experience of relapsed/refractory ATLL, patients appear to have modest response rate to a second-line chemotherapy and these responses are not long lasting. In our patient population, risk of CNS disease at presentation was low (5%) but the incidence approaches 17.3% at the time of relapse. Administration of prophylactic intrathecal methotrexate showed a trend towards reducing the incidence of CNS disease although the results were not statistically significant.

Disclosures
No relevant conflicts of interest to declare.