Evaluation of two prognostic indices for adult T-cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan

Abstract

Aggressive adult T-cell leukemia/lymphoma (ATL) has an extremely poor prognosis and is hyperendemic in Okinawa, Japan. This study evaluated two prognostic indices (PIs) for aggressive ATL, the ATL-PI and Japan Clinical Oncology Group (JCOG)-PI, in a cohort from Okinawa. The PIs were originally developed using two different Japanese cohorts that included few patients from Okinawa. The endpoint was overall survival (OS). Multivariable Cox regression analyses in the cohort of 433 patients revealed that all seven factors for calculating each PI were statistically significant prognostic predictors. Three-year OS rates for ATL-PI were 35.9% (low-risk, n = 66), 10.4% (intermediate-risk, n = 256), and 1.6% (high-risk, n = 111), and those for JCOG-PI were 22.4% (moderate-risk, n = 176) and 5.3% (high-risk, n = 257). The JCOG-PI moderate-risk group included both the ATL-PI low- and intermediate-risk groups. ATL-PI more clearly identified the low-risk patient subgroup than JCOG-PI. To evaluate the external validity of the two PIs, we also assessed prognostic discriminability among 159 patients who loosely met the eligibility criteria of a previous clinical trial. Three-year OS rates for ATL-PI were 34.5% (low-risk, n = 42), 9.2% (intermediate-risk, n = 109), and 12.5% (high-risk, n = 8). Those for JCOG-PI were 22.4% (moderate-risk, n = 95) and 7.6% (high-risk, n = 64). The low-risk ATL-PI group had a better prognosis than the JCOG-PI moderate-risk group, suggesting that ATL-PI would be more useful than JCOG-PI for establishing and examining novel treatment strategies for ATL patients with a better prognosis. In addition, strongyloidiasis, previously suggested to be associated with ATL-related deaths in Okinawa, was not a prognostic factor in this study.

Keywords: ATL-PI; JCOG-PI; Okinawa; adult T-cell leukemia/lymphoma; strongyloidiasis.

Figure 1

Schematic diagram of patients with aggressive adult T‐cell leukemia/lymphoma (ATL). A total of 659 patients who received a diagnosis of aggressive ATL in Okinawa prefecture between January 2002 and December 2011. Among them, 615 were treated and 44 were not; 226 patients were excluded because of missing data required to calculate the ATL prognostic index (ATL‐PI) or Japan Clinical Oncology Group (JCOG)‐PI. Prognostic factors were analyzed and validated with ATL‐PI and JCOG‐PI among the remaining 433 patients

Figure 2

Overall survival rate and median survival time in this cohort study of patients with aggressive adult T‐cell leukemia/lymphoma (ATL) in Okinawa, Japan. Median survival time (MST) and 3‐y overall survival (3yOS) rate of the 433 patients with aggressive ATL were 0.5 y and 12.3%, respectively

Figure 3

Overall survival curves of patients with aggressive adult T‐cell leukemia/lymphoma (ATL) in Okinawa according to the ATL prognostic index (ATL‐PI) (A) and Japan Clinical Oncology Group (JCOG)‐PI (B). According to the ATL‐PI, the median survival times (MSTs) were 2.1, 0.6, and 0.3 y, and the 3‐y overall survival (3yOS) rates were 35.9%, 10.4%, and 1.6% for patients at low risk, intermediate risk, and high risk, respectively (P < .0001). According to the JCOG‐PI, MSTs were 0.8 and 0.4 y and 3yOS rates were 22.4% and 5.3% for patients at moderate and high risk, respectively (P < .0001)