Hepatosplenic T-Cell Lymphoma: Clinicopathological Features and Treatment Outcomes: Report From The North American Peripheral T-Cell Lymphoma Consortium
Authors: Shustov Andrei R. , Wilson Wyndham H , Beaven Anne W , Savage Kerry J. , Carson Kenneth R. , Hernandez-Ilizaliturri Francisco J. , Cherian Sindhu , Gooley Ted A. , Vose Julie M 
Published: October 2019

Abstract

Background
Hepatosplenic T-cell lymphoma (HSTCL) is an exceedingly rare subtype of mature T-cell lymphomas with dismal outcome despite combination chemotherapies. It is characterized by frequent involvement of splenic red pulp, liver sinusoids and bone marrow; nodal and other extranodal sites are rarely affected. Patients frequently present with cytopenias and B–symptoms. Malignant cells are medium-sized mature T-cells with cytotoxic phenotype. Most frequent chromosomal abnormalities are isochromosome 7q and trisomy 8. Gamma-delta phenotype is found in the majority of cases, but alpha-beta variant has been reported. All studies to date report very poor responses to standard lymphoma protocols and only few survivors after stem cell transplantation. We report the largest series of this rare malignancy to date including clinicopathologic features and treatment outcomes collected by several North American Institutions.

Methods
This is a retrospective multi-center cohort study conducted by the participating institutions. Data was collected from charts of previously diagnosed and treated HSTCL patients. Chart review protocol was approved by Institutional Review Boards of participating centers and a waiver of consent was obtained. University of Washington served as coordinating center for data collection and analysis. We obtained the following data from patients' medical charts: demographic characteristics, histologic findings, immunophenotypic and molecular analysis, cytogenetics, treatment regimens and disease responses, clinical outcomes and survival. Summary statistics was used to describe the clinical, demographic and pathological characteristics. Response was defined using the International Workshop NHL criteria. For survival analyses, overall survival (OS) was time between the diagnosis and the patient's last follow up or death. The Kaplan-Meier method was used to estimate survival distributions.

Results
Forty-two patients were identified, 24 male and 18 female, with the median age of 35 (range, 17-79) years. Twenty-six (62%) patients were Caucasian, 8 (19%) were Asian, 6 (14%) were African American, and 2 (5%) were other. Splenomegaly was reported in 39/42 patients (93%), hepatomegaly in 23/40 (58%), and bone marrow involvement in 32/39 (82%) patients. Lymph nodes were involved in only 12/40 (30%) patients. Anemia was present (median HCT=30.5%) in 30/37 (81%), leucopenia (median WBC=4.3K/ul) in 9/41 (22%), thrombocytopenia (median platelet count = 80K/ul) in 33/41 (80%) of reported patients. Abnormal liver function tests were found in 31/38 (82%) of the reported cases. Gamma-delta and alpha-beta phenotype was found in 84% and 16% of reported cases (n=37), respectively. Isochromosome 7q was found in 6/23 (26%) of patients while 6/23 (26%) had other aberrations. History of immunosuppressive therapy was present in 13/42 (31%) reported patients, including 4 patients receiving prior therapy with TNF-alpha inhibitors. Nine out of 42 patients (21%) had history of inflammatory bowel disease. All patients received multi-agent chemotherapy. Overall response rate (ORR) to initial therapy was 63%, with 44% achieving complete remission (CR). Twenty-three out of 42 (55%) reported patients underwent autologous (n=2) or allogeneic (n=19) stem cell transplantation, and 2 underwent both. Twenty-nine (69%) patients have died. Of note, all but one of the surviving patients have undergone allogeneic stem cell transplantation. With the median follow-up of 56 (range 15-105) mo for living patients, the median OS was 15.8 mo (Fig. 1). Detailed histo-pathologic data and treatment regimens will be reported at the meeting.

Conclusions
This is the largest study to date of hepatosplenic T-cell lymphomas. This is a rare malignancy associated with poor outcomes after contemporary treatments. Response to initial therapies is suboptimal, relapses are frequent and median overall survival is short. Stem cell transplantation in first remission should be considered for all patients achieving response to initial therapy. Novel therapies are needed to improve outcomes.

Disclosures:
No relevant conflicts of interest to declare.