Adult T-cell leukemia/lymphoma (ATLL) is a rare, aggressive peripheral T-cell lymphoma, affecting patients from HTLV-1 endemic areas including Japan, the Caribbean, Latin America, Africa, and Northern Iran. Most of the literature regarding prognosis and management reflects experience from Japan, where the demographic and clinicopathologicfeatures may differ from other endemic countries. There are limited data on clinical presentation and treatment outcomes of patients from North America (NA) with ATLL (Philips, Cancer, 2010). Based on the available literature, however, prognosis remains poor, with few effective chemotherapeutic options. We performed a retrospective analysis of patients with ATLL presenting to a NA tertiary care center. Our primary objectives were to (a) describe patient demographics, ATLL subtype, and presentation characteristics, (b) identify progression free survival (PFS) and overall survival (OS), (c) identify the impact of consolidation antiviral therapy on duration of response in this high-risk patient population.
Patients with ATLL were identified from prospectively populated lymphoma and leukemia databases at Princess Margaret Cancer Centre (PMCC) referred for primary therapy; patients referred at relapse or for consideration of treatment in first response were also included if they received therapy at PMCC. Patients were included if they met current criteria for ATLL and had a positive HTLV-1 antibody test. Additional data were collected from patient charts including ethnicity, ATLL subtype, initial treatment, and response to therapy. Descriptive statistics were used to evaluate demographic data, ATLL subtype,immunophenotype, first-line therapy, and response. In patients who achieved a partial or complete response following first line therapy, a t-test was used to identify the impact of consolidative antiviral therapy on duration of response. Twenty-eight patients received their first-line therapy at PMCC and Kaplan-Meyer estimates were used to calculate the PFS and OS for this population.
Forty-three patients with ATLL were referred to PMCC from 1993 to 2014. Median age at diagnosis was 46 years (20-69) and 55.8% were females (Table 1). The majority were of Caribbean descent (63%), followed by African (5%), Asian (3%), Middle Eastern (3%), or undocumented country of origin (28%). ATLL subtype consisted of lymphomatous (44%), acute (35%) and smoldering (2%); subtype could not be fully determined in 28% of cases. 88% of patients were treated with front-line chemotherapy and 12% treated with upfront antiviral therapy alone (interferon alpha with or without antiretroviral therapy). At presentation, 16 (37%) patients had bone marrow involvement, 11 (26%) had CNS involvement, 5 (12%) had lytic lesions, 5 (12%) had skin involvement, and 7 (16%) had hypercalcemia.
Immunophenotype based on flow cytometry of peripheral blood or lymph node biopsy was available for 27 patients. Twelve patients (44%) were positive for CD4, CD5, CD3, CD2 and CD25; 3 were double positive for CD4 and 8. The majority of patients were CD7 negative (78%) and commonly CD8 negative (44%). Three patients were also negative for CD25 (11%).
Following primary chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone, 30% (13 of 43) patients achieved a partial or complete remission; the remaining 30 patients experienced disease progression during or at completion of chemotherapy. All responding patients experienced disease relapse; median duration of response was 17.4 months. Five patients (38.5%) received consolidative antiviral therapy, however, there was no statistically significant difference in duration of response (p=0.20). Twenty eightpatients received first-line therapy at PMCC. Median PFS for this group was 0.42 years (95% confidence interval 0.16 to 1.25) (Figure 1). Median OS 1.29 years (95% confidence interval 0.57 to 2.26) (Figure 2).
The outcome of patients with ATLL in this retrospective observational study are very poor. Within the limits of the nationalities of patients referred to ourcenter, NA ATLL patients present with acute or lymphomatous subtypes, and have a high incidence of CNS involvement. Complete response rate to chemotherapy commonly used in other T cell lymphomas is low, and incorporation of alternative regimens and antibody therapies should be tested in primary therapy of ATLL.
Kuruvilla: Celgene: Consultancy, Honoraria; Amgen: Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche Canada: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Merck: Honoraria; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Honoraria. Kukreti:Lundbeck: Honoraria; Amgen: Honoraria; Celgene: Honoraria.