Incidence, clinical findings, and survival of hepatosplenic <scp>T</scp>‐cell lymphoma in the <scp>U</scp>nited <scp>S</scp>tates
Authors: Urshila Durani, Ronald S. Go
Journal: American Journal of Hematology (2017)

Hepatosplenic T-cell lymphoma (HSTCL) is an uncommon disease whose true incidence is unknown. Most of our knowledge of HSTCL is derived from case reports and small case series. Those affected tend to be younger and male.1, 2 A majority have advanced disease at presentation, marked by hepatosplenomegaly, bone marrow involvement, B symptoms, elevated lactate dehydrogenase (LDH), and thrombocytopenia.1-4 HSTCL has been associated with chronic immunosuppression or immune dysregulation, including solid organ transplant and the use of biologics.2, 3 The prognosis is poor, with median overall survivals (OS) ranging from 3 to 28 months.1, 3 Unfortunately, treatment is mostly extrapolated from clinical trials of peripheral T-cell lymphoma.1 Various anthracycline-based regimens have been used without much success.1, 3, 4 Hematopoietic stem cell transplant (SCT) has been shown in observational studies to produce a more sustained remission and possibly OS benefit compared to chemotherapy alone, but no comparative trials have been performed.4, 5 Herein we use two national databases to describe the incidence, clinical features, and outcomes of patients with HSTCL in the US. We calculated the incidence rates (case/100 000 000) age-adjusted to the US 2000 population using SEER*STAT software version 8.1.5 and included 2000-2012 data from the Surveillance, Epidemiology, and End Results (SEER) Program, a population-based cancer registry funded by the National Cancer Institute. We obtained patient level data using the National Cancer Data Base (NCDB), an oncologic database supported by the American College of Surgeons and American Cancer Society and representing 70% of incident cancers in the US. All patients aged 18 and older with a diagnosis of HSTCL (International Classification of Diseases for Oncology version 3 Code 9716/3) from 1998 to 2011 were included. Patients with a classification of class_of_case = 0 were excluded as they were not treated at the same facility of diagnosis. Based on our study, the incidence of HSTCL increased from 1.8 in year 2000 to 15.2 in year 2012 (P < .05) (Figure 1). Blacks had the highest incidence rate (18.9) followed by Asians/Pacific Islanders (11.4) and Whites (6.1). Compared to Whites, Blacks had a significantly higher incidence (rate ratio: 3.11; 95% confidence interval [CI]: 1.84-5.15), while Asians had a similar incidence (rate ratio: 1.87; 95% CI: 0.89-3.59). This is a graph of the incidence from 2000 to 2012 (using SEER) and absolute number of NCDB cases of HSTCL from 1998 to 2011. Incidence is depicted using the dotted line graph and absolute number of NCDB cases is depicted using the bar graph. Between 1998 and 2011, 185 patients with newly diagnosed HSTCL were identified in the NCDB. At the time of the analysis, 149 patients (81%) had died. The median follow-up period for those who were still alive was 56.4 months (interquartile range [IQR]: 38.0-72.9). The median age at diagnosis was 47.0 years (IQR: 30.0-62.0) and most (68.6%) were males. Only 13 patients (7.0%) had a Charlson–Deyo comorbidity score of 2 or more (though data on Charlson–Deyo scores are only available after 2002). One hundred thirty-six patients (73.5%) received chemotherapy alone as first-line therapy, while 12 (6.5%) also received consolidative SCT (four autologous, seven allogeneic, and one unknown type). The one- and five-year survival rates were 40.4% (95% CI: 33.3-47.4) and 14.6% (95% CI: 9.2-21.1), respectively, and the median OS was 8.8 months (95% CI: 6.4-11.2). We performed univariate analyses to determine the effects of age, sex, race, income, insurance status, travel distance to facility, and use of SCT as part of initial therapy on OS (Table 1). Compared to their counterparts, those who were females (HR = 0.58; 95% CI: 0.40-0.84; P < .01), had Medicaid insurance (HR = 0.61; 95% CI: 0.39-0.97; P = .04), or received SCT (HR = 0.35; 95% CI: 0.19-0.65; P < .01) had better OS. Female sex, receipt of SCT, and top income quartile were all significant predictors of decreased mortality in a multivariable analysis (Table 1). The median OS for patients who did and didn't receive a SCT were 34.4 and 6.7 months, respectively. The median OS for the whole group did not improve over time [7.6 and 9.0 months for 1998-2004 and 2005-2011, respectively (P = .13)]. Our study is the first to use a nationally representative sample to define the incidence of HSTCL in the US and examine trends over time. One previous study described the incidence of HSTCL to be 0.3 per 1 000 000 person-years.6 However, the authors used a regional cancer registry which only had six documented cases between 2000 and 2006. The increased incidence over time described in our study could partly be due to increased recognition of the disease entity and use of immunosuppressive agents. It is unclear why Blacks are disproportionately affected. Our study did not find a significant improvement in OS for HSTCL patients over the decade studied. From previous studies we know that patients receive a variety of anthracycline-based regimens.2, 3 None of these seem to deliver a significant survival benefit, though comparative studies and trials have not been done. In univariate and multivariate analyses, SCT was associated with a better OS, consistent with previous reports.1, 4, 5 Our study is the largest one to compare SCT to non-SCT patients in a real-world setting and adds to the growing literature in support of SCT in this population. One might argue that patients who received SCT as initial therapy are likely healthier and their improved OS may be in part due to this, though our population was relatively young and had a low Charlson–Deyo comorbidity score. Our study has several limitations. First, given our small sample size, our statistical analysis was limited. Also, given the difficulty in diagnosis of HSTCL, our cohort may not be representative of the entire HSTCL population. However, ours is the largest study to date to describe the predictors of mortality in HSTCL, and this study can be expanded as more cases accumulate over time. In addition, given the limitations of the NCDB itself, we were unable to provide details of the initial chemotherapy given or relapse. In conclusion, the incidence of HSTCL has at least doubled in the past decade with the highest predilection among Blacks. The OS remains poor and disturbingly has not improved over time. The use of SCT may be associated with a better outcome, supporting the earlier findings from smaller retrospective studies. We expect a further increase in the incidence of HSCTL as more patients in the US receive organ transplants and become immunosuppressed. No conflicts of interest or funding to disclose. Urshila Durani (co-author) contributed to data analysis and manuscript authorship; Ronald S. Go (co-author) contributed to study planning, review of data, and manuscript authorship; Adam C. Bartley, a statistician at Mayo Clinic, contributed to the editorial process of manuscript preparation and suggestions on data presentation.