Prognosis of patients with adult T-cell leukemia/lymphoma in Japan: A nationwide hospital-based study

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasm and is classified into four subtypes (acute, lymphoma, chronic, and smoldering) according to the Shimoyama classification, established in 1991 through several nationwide surveys based on the clinical diversity of patients diagnosed in 1983-1987 in Japan. Thereafter, no such studies have been conducted. Recently, we conducted a nationwide hospital survey using the method of the 1980s studies, collected baseline data on 996 ATL patients diagnosed in 2010-2011 from 126 hospitals, and reported their unique epidemiological characteristics. Here, we report the follow-up results of registered ATL patients with the goal of evaluating current prognoses and treatment modalities as of 2016-2017. Of 770 evaluable patients, 391 (50.8%) had acute-type, 192 (24.9%) had lymphoma-type, 106 (13.8%) had chronic-type, and 81 (10.5%) had smoldering-type ATL. The initial therapy regimens used for acute/lymphoma-type ATL were vincristine, cyclophosphamide, doxorubicin and prednisone, followed by doxorubicin, ranimustine, and prednisone and then by vindesine, etoposide, carboplatin, and prednisone (VCAP-AMP-VECP)-like in 38.5/41.7% and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like in 14.6/13.7% of patients. Allogeneic hematopoietic stem cell transplantation was used to treat 15.9/10.4% of acute/lymphoma-type ATL patients. The 4-year survival rates (the median survival time, days) for acute-, lymphoma-, unfavorable chronic-, favorable chronic-, and smoldering-type ATL were 16.8% (252), 19.6% (305), 26.6% (572), 62.1% (1937), and 59.8% (1851), respectively. The 4-year survival rates for acute- and lymphoma-type ATL improved compared with those reported in 1991, but those for chronic- and smoldering-type ATL were not. Further efforts are warranted to develop more efficient therapeutic strategies to improve the prognosis of ATL in Japan.

Keywords: ATL; HTLV-1; Japanese nationwide survey; clinical subtypes; prognosis.

Figure 1

A, Study flow chart for patient inclusion/exclusion. B, Overall survival (OS) and median survival time (MST) by adult T‐cell leukemia/lymphoma (ATL) subtype

Figure 2

Survival analysis of acute and lymphoma adult T‐cell leukemia/lymphoma (ATL) subtypes. A, Overall survival (OS) in acute ATL by age stratum at diagnosis. B, OS in acute ATL by allogeneic hematopoietic stem cell transplantation (allo‐HSCT) status among patients aged < 70 y. C, OS in lymphoma ATL by age stratum at diagnosis. D, OS in lymphoma ATL by allo‐HSCT status among patients aged < 70 y. Abbreviations: CI, confidence interval; MST, median survival time; NR, not reached

Figure 3

Survival analysis of chronic adult T‐cell leukemia/lymphoma (ATL) subtype. A, Overall survival (OS) in chronic ATL according to favorable and unfavorable subtype. B, OS in favorable chronic ATL by age. C, OS in unfavorable chronic ATL by age. D, OS in unfavorable chronic ATL by allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in patients aged < 70 y. Abbreviations: CI, confidence interval; MST, median survival time; NR, not reached

Figure 4

Summary of outcomes of adult T‐cell leukemia/lymphoma (ATL) patients based on 4‐year overall survival (OS) in Japan by subtype: acute‐type (A), lymphoma‐type (B), chronic‐type (C), and smoldering‐type (D). The percentage in each box represents the estimated proportion of patients. Results based on the outcomes of patients who received any chemotherapy are shown for acute‐ and lymphoma‐type ATL. ^aDied despite allogeneic hematopoietic stem cell transplantation (allo‐HSCT) (only patients aged < 70 y). ^bDied despite chemotherapy without allo‐HSCT. ^cReceived chemotherapy during observation period. ^dDied despite chemotherapy. ^eAlive without chemotherapy in patients with unfavorable chronic‐type ATL. Abbreviations: Rate at 4‐y, survival rate at 4‐y follow‐up; UK, unknown