Real-World Data in a Prospective Clinical Observation Study for Newly Diagnosed Adult Acute Lymphoblastic Leukemia, the JALSG ALL-CS-12 : Advanced Age Is a Poor Prognostic Factor
Authors: Hatta Yoshihiro , Hayakawa Fumihiko , Yamazaki Etsuko , Murayama Tohru , Saito Takeshi , Takada Satoru , Dobashi Nobuaki , Ota Shuichi , Yokoyama Yasuhisa , Tanaka Masatsugu , Sato Shinya , Ohtake Shigeki , Sakaida Emiko , Maeda Yoshinobu , Yamauchi Takahiro , Matsumura Itaru , Miyazaki Yasushi , Kiyoi Hitoshi 
Published: December 2023

Background
In the past 20 years, many clinical trials with pediatric type chemotherapy have improved outcome in adult ALL patients. However, they were selected patients with good performance status, less comorbidity, and tolerance to intensive chemotherapy. In the real-world, many ALL patients did not receive intensive chemotherapy for various reasons especially in elderly patients. Because the aging of the population is increasing remarkably in Japan, it is important to clarify the current overall treatment results and consider new treatment strategies for all ALL patients. Real-world data in ALL including patients not participating in the clinical trials have rarely been reported. Therefore, Japan Adult Leukemia Study Group (JALSG) conducted JALSG ALL-CS-12 study, a prospective clinical observation study for newly diagnosed adult ALL with large number of patients.
Methods
All newly diagnosed ALL patients according to the 2008 edition of WHO classification aged 15 years and older were prospectively registered by JALSG after informed consent. The study was approved by institutional ethical board and conducted in accordance with the Declaration of Helsinki.
Results
Nine-hundred and fifty-four ALL patients were accrued between April 2012 and August 2017. Nineteen patients were excluded for misdiagnosis including CML blast crisis, history of chemotherapy, lack of data, and duplicate registration. Among the remaining 935 patients, 209 were over 65 years old patients generally not focused on clinical trials. Four-hundred and sixty-nine were Philadelphia chromosome negative B-ALL (Ph-), 130 were T-ALL, 293 were Ph +ALL, and 44 were Burkitt leukemia. Median age was 45 years (range 15-89) in B-ALL (Ph-), 33 (15-80) in T-ALL, 60 (15-89) in Ph +ALL, and 60 (15-91) in Burkitt leukemia with significantly younger in T-ALL patients as has been reported previously. Chemotherapy was not performed in 23 patients in B-ALL (Ph-), 3 in T-ALL, 4 in Ph +ALL, and 3 in Burkitt leukemia. Fifteen of them were over 70 years old. CR rate was comparable in four disease cohorts, 81.7% in B-ALL (Ph-), 78.7% in T-ALL, 88.7% in Ph +ALL and 74.4% in Burkitt leukemia, respectively. However, in the patients with 75 years or older, CR rate was low, 42.4% in B-ALL (Ph-), 64.5% in T-ALL, 64.5% in Ph +ALL and 42.9% in Burkitt leukemia, respectively. Cumulative incidence of relapse at 5 years was 38.8% in B-ALL (Ph-), 20.8% in T-ALL, 43.8% in Ph +ALL, and 50.9% in Burkitt leukemia, respectively (p&lt;0.05). 5-year event free survival (EFS) and overall survival (OS) rates were 46.1% and 52.6% in B-ALL (Ph-), 55.4% and 61.6% in T-ALL, 44.5% and 52.5% in Ph +ALL, and 26.2% and 36.0% in Burkitt leukemia, respectively (p&lt;0.05). When the age of the patients was classified in increments of 10 years, EFS was worse as the age increased in B-ALL (Ph-), T-ALL, and Ph +ALL (table).
Conclusions
JALSG ALL-CS-12 study is the large prospective cohort study and provides important information that is less to the inherent selection bias. The incidence and median age of the four types of leukemia cohorts in Japan were comparable to those in European reports. Although CR rate was acceptable despite the inclusion of patients outside of clinical trials, EFS was strongly dependent on age. Post-remission treatment and management of complications are assignments to be solved especially for elderly ALL patients.
Acknowledgement
We thank Ms. Ryoko Fujiyoshi in Nagasaki data center for collecting CRFs.