These results suggest that SAHA has activity in hematologic malignancies including HD and select subtypes of non-Hodgkin's lymphoma.

BACKGROUND:To define the clinicopathologic and prognostic features of patients with human T-cell lymphotropic virus type-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) in North America, standard criteria were used to identify patients with ATLL. METHODS: Statistical analyses used included descriptive statistics, Kaplan-Meir survival analysis, and recursive partitioning. RESULTS: Eighty-nine patients were identified between August 1992 and May 2007, including 37 (41.6%) males and 52 (58.4%) females with a median age of 50 years (range, 22-82 years). All but 6 patients had immigrated to the United States from the Caribbean, Latin America, or Africa. The acute subtype predominated (68.5%). The majority of patients received a combination-alkylator-based chemotherapy regimen in the front-line setting (72.6%). The most common regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone at standard doses or attenuated and/or with methotrexate (CHOP-like), which produced an overall response rate of 64.1%. Despite initial responses to therapy, the median overall survival for all subtypes was 24 weeks (range, 0.9-315 weeks). Although the International Prognostic Index and Prognostic Index for peripheral T-cell lymphoma unspecified identified subsets of patients, these models were not completely predictive. A recursive partitioning analysis was performed on the data, which successfully identified 3 prognostic categories based on Eastern Cooperative Oncology Group performance status, stage, age, and calcium level at diagnosis. CONCLUSIONS: This series proposed a new prognostic model for patients with HTLV-1-associated ATLL and confirmed a poor outcome for these patients in North America. Cancer 2010;116:3438-46.

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Adult T cell Leukemia/Lymphoma (ATLL) is a rare manifestation of Human T-Lymphotropic Virus type 1 (HTLV-1) which is endemic in Japan, the Caribbean, and regions of Africa and Latin America. Endemic regions have also been identified in the US, primarily where immigrants of endemic countries reside. The NYC metropolitan area has the greatest number of Caribbean-born immigrants to the US which has formed the basis for this retrospective review. A diagnosis of ATLL was made according to the following criteria: a clinical history consistent with ATLL; a positive HTLV-1 antibody by ELISA and Western Blot, or evidence of HTLV-1 proviral integration by PCR; and histological findings compatible with ATLL. A total of 89 patients were identified at 3 institutions in NYC from 8/92 to 5/07. There were 37 men and 52 women with a median age of 50y (range 22 to 82y). All but 6 patients had immigrated to the US from the Caribbean, Latin America or Africa, and the majority were from Jamaica (25.8%) and the Dominican Republic (19.1%). The acute subtype predominated (68.5%), followed by the lymphomatous (20.2%), chronic (6.8%) and smoldering (4.5%) subtypes. The most common presenting symptoms were lymphadenopathy (80.9%) and skin rash (39.3%) and the median ECOG performance status was 3. WBC counts ranged from 3.0 to 334.0 x 109/l (median of 12.5 X 109/l). Hypercalcemia was seen in 71.9% of patients (median calcium level of 13.5 mg/dl, range 9.8 to 27.0 mg/dl). Twenty-eight patients (31.5%) had CNS involvement during their course. The median International Prognostic Index (IPI) was 4. Most patients received a combination-alkylator based chemotherapy regimen in the frontline setting (ex: CHOP) (61.3%), with an overall response rate (ORR) to the frontline treatment of 58.2%. Twenty patients (20.2%) received AZT and IFN at sometime during their course with an ORR of 25%. Twelve patients (13.5%) received a biologically based therapy at sometime during their course, with only two patients achieving a partial response (to alemtuzamab and denileukin diftitox). Despite initial responses to therapy, the median overall survival for all subtypes was 6 mos (range 0.5 to 78.5 mos). Median survival for specific subtypes was noted to be: 4 mos for the acute subtype (range 0.5 to 78.5 mos); 9 mos for the lymphomatous subtype (range 1 to 63 mos), 17 months for the chronic subtype (range 5 to 22 mos) and 34 mos for the smoldering subtype (range 16 to 48 mos). Conclusion: This retrospective series represents one of the largest North American experiences to date among primarily Caribbean descendants. Interestingly, when placed into the context of other experiences published over the past 30 years, it is clear there has been little to no change in the outcome of patients diagnosed with this disease. In fact, this population, with a median overall survival of only 6 mos, represents one of the poorest outcomes reported for any sub-type of lymphoma. These data suggest that radically new ATLL directed therapies are needed. The recent development of several new T-cell active agents, in addition to other strategies (ex: transplantation) need to be specifically studied in this population.