Hepatosplenic T-Cell Lymphoma: Clinical Characteristics and Treatment Outcome.
Authors: Falchook Gerald S. , Champlin Richard , Hagemeister F.B. , Hosing Chitra , Kwak Larry W. , O’Brien Susan , Rodriguez Maria Alma , Verstovsek Srdan , Pro Barbara 
Published: October 2019

Abstract
Hepatosplenic T-cell lymphoma is a rare peripheral T-cell lymphoma, and less than 100 cases have been described in the literature since the entity was first proposed in 1990. This condition is characterized by malignant T-cell proliferation in the sinusoids of the liver, sinuses and red pulp of the spleen, and sinuses of the bone marrow. The commonly reported T-cell phenotype is CD2+, CD3+, CD4−, CD5−, CD7±, CD8−, with either gamma-delta or alpha-beta T-cell receptor expression. Associated cytogenetic abnormalities include isochromosome 7q with or without trisomy 8. Approximately 10–20% of patients have a history of immunocompromise. Treatment to date with standard anthracycline containing chemotherapy regimens has been disappointing with variable response rates, high relapse rates, and a short median survival. An optimal treatment strategy for this small patient population has not yet been determined.
Methods: Eleven cases of pathologically confirmed hepatosplenic T-cell lymphoma seen at M.D. Anderson Cancer Center between January 1990 and June 2006 were identified in the institution’s database. Clinical characteristics and treatment results were retrospectively reviewed.
Results: The mean age at the time of diagnosis was 35.3 years (range 8 – 58 years). Six patients were male and five were female. Seven patients had the gamma-delta T-cell receptor phenotype, and three patients had the alpha-beta T-cell receptor phenotype. Cytogenetic abnormalities observed included t(7;14)(q34q13), 46,idem,del(2)(q32q37), 45XY,der(13;14)(q10;q10), 45XY,i(7)(q10),der(13;14)(q10;q10), del(22q).ish22(WCP22x2). One patient had lymphomatous involvement of the skin, a finding not previously reported in hepatosplenic T cell lymphoma. Two patients had a history of significant immunocompromise, including one patient with Sjogren’s disease treated intermittently with prednisolone and methotrexate, and one patient with Crohn’s disease on chronic treatment with mercaptopurine. Complete responses (CR) were achieved in four out of eight patients who received chemotherapy and whose complete records were available. CRs were achieved with the following regimens: (1) Sequential IDSHAP/AMDBIDCOS/MINE, (2) CHOP/methotrexate and autologous stem cell transplant, (3) CHOP, (4) pentostatin/campath and allogeneic stem cell transplant. PET scans in 3 patients and Gallium scans in 5 patients did not correlate with disease activity or clinical response. Mean duration of CR was 8 months (range 2 – 14+ months). Mean overall survival was 11.4 months (range 3 – 25 months), with one patient still alive and in remission at 20 months.
Conclusion: In one of the largest series of hepatosplenic T-cell lymphoma patients, we confirm the aggressive clinical course of this subtype of peripheral T-cell lymphoma occurring in a young patient population. We discovered a near-equal incidence of this disease in males and females, contrary to results in earlier series which suggested this disease is usually diagnosed in males. Standard chemotherapy treatment strategies resulted in poor outcomes. However, survival may be improved upon with newer strategies such as the use of alemtuzumab, pentostatin, and high dose chemotherapy with stem cell rescue. New therapeutic strategies are needed to improve the outcome of patients with hepatosplenic T-cell lymphoma.