The Significance of Complete Clearance of Peripheral Blasts after 7 Days of Prednisolone in Children with Acute Lymphoblastic Leukemia: Tokyo Children’s Cancer Study Group (TCCSG) Study L99-15.
Authors: Koh Katsuyoshi , Ohara Akira , Manabe Atsushi , Ikuta Kouichiro , Hanada Ryouji , Yabe Hiromasa , Kinoshita Akitoshi , Koike Kenichi , Okimoto Yuri , Noguchi Yasushi , Kajiwara Michiko , Takahashi Hiroyuki , Sugita Kanji , Fukushima Takashi , Isoyama Keiichi , Saito Masahiro , Kikuchi Akira , Ota Setsuo , Kumagai Masaaki , Hayashi Yasuhide , Saito Tomohiro , Tsuchida Masahiro 
Published: April 2020

BACKGROUND: A rapid clearance of leukemic blasts in the peripheral blood (PB) is well known to be correlated with a good prognosis in children with ALL. Most groups use a cut-off of Day 8 PB blasts as 1000/μ L. It is possible that patients with no blasts may have an even better outcome. In L99-15 study, we tested the utility of a cut-off of 0 (zero) blasts to stratify children with ALL.

OBJECTIVE: To evaluate the significance of complete clearance of peripheral blasts after 7 days of PSL in children with ALL.

PATIENTS AND METHODS: Children newly diagnosed as ALL between 1999 and 2003 were consecutively enrolled on the TCCSG L99-15 study. All patients initially received 7 days prednisolone 60mg/m2 monotherapy (without intrathecal therapy) and day 8 PB blasts were classified into 3 categories, 0, 1-999, 1000 or more/μL. Risk stratification was based on the age, initial white blood cell (WBC) count, immunophenotype, cytogenetics and the response to prednisolone.

Induction treatment consisted of a standard 4-drug regimen in standard-risk group (SR) groups whereas cyclophosphamide was added in high-risk group (HR) and very high-risk group (HEX). After induction, SR and HR patients received BFM-type early intensification, consolidation, reinduction, and maintenance therapy. HEX patients received early intensification and intensive rotational consolidation therapy including AML-type consolidation, and no maintenance therapy. Total duration of therapy was 3 years for SR, 2 years for HR, and 1year for HEX patients. Allogeneic stem cell transplantation was indicated approximately in 50% of the HEX patients.

RESULTS: Totally, 267 (35%) out of 770 children were categorized into SR, 317 (41%) into HR and 186 (24%) into HEX. Remission was obtained in 259 (97%) patients in SR, 311 (98%) in HR and 171 (92%) in HEX. Event-free survival (EFS) (SE) at 4 years was 80.5% (1.7%) in B precursor ALL (n = 669), and 66.0% (5.1%) in T ALL (n = 92).

In B precursor ALL, patients with day 8 PB blasts as 0 were 129 (44%) out of 295 initial SR group, 85 (29%) out of 289 initial HR group, 6 (10%) out of 59 initial HEX group, and 4y-DFS was 91.1% (2.6%), 89.4% (3.6%), 83.3% (15.2%), respectively. In T ALL, patients with day 8 PB blasts as 0 were 22 (26%) out of 84, and 4y-DFS was 100% (0%).

CONCLUSION: Patients with Day8 PB blasts as 0 (zero) constituted about 30% of all the cases with childhood ALL. Excellent outcome (4-year EFS of 90%) was obtained for those with 0 blasts.

Initial Risk Groups WBC/age 1–6y 7–9y 10y– K = 1,000 μL −20K SR HR HR 20–50K HR HR HR 50–100K HR HR HEX 100k– HEX HEX HEX Final Risk Groups day 8 blast 0 1–999 1000– HEX/SCT: HEX and allogeneic stem cell transplantation Initial Risk Groups non-T/SR SR SR HR non-T/HR HR HR HEX non-T/HEX HR HEX HEX/SCT T-ALL HR HEX HEX/SCT