TY - JOUR
T1 - A risk-stratified therapy for infants with acute lymphoblastic leukemia
T2 - a report from the JPLSG MLL-10 trial
AU - Tomizawa, Daisuke
AU - Miyamura, Takako
AU - Imamura, Toshihiko
AU - Watanabe, Tomoyuki
AU - Saito, Akiko Moriya
AU - Ogawa, Atsushi
AU - Takahashi, Yoshihiro
AU - Hirayama, Masahiro
AU - Taki, Tomohiko
AU - Deguchi, Takao
AU - Hori, Toshinori
AU - Sanada, Masashi
AU - Ohmori, Shigeru
AU - Haba, Masami
AU - Iguchi, Akihiro
AU - Arakawa, Yuki
AU - Koga, Yuhki
AU - Manabe, Atsushi
AU - Horibe, Keizo
AU - Ishii, Eiichi
AU - Koh, Katsuyoshi
N1 - Funding Information:
This study was supported by a grant for clinical cancer research from the Ministry of Health, Labour, and Welfare of Japan (H23-KakushintekiGan-Ippan-014) (K.H.), grants for Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (15ck0106071h0002) (A.M.) and (18ck0106436h0001) (T.M.), a grant from the National Center for Child Health and Development (30-1) (D.T.), and a research grant from the Children’s Cancer Association of Japan.
Funding Information:
The authors thank all of the JPLSG and the Japan Children?s Cancer Group investigators involved in the MLL-10 trial; Yoshie Okano, Noriko Sato, and Kaori Nagai from the Organization for Supporting Clinical Research data center for managing trial data; and the COG investigators, particularly Stephen P. Hunger, Patrick Brown, and Bruce M. Camitta, for providing information on AALL0631 protocol. The authors also thank the medical editor from the Department of Education for Clinical Research of the National Center for Child Health and Development for his assistance with editing this manuscript. This study was supported by a grant for clinical cancer research from the Ministry of Health, Labour, and Welfare of Japan (H23-KakushintekiGanIppan-014) (K.H.), grants for Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (15ck0106071h0002) (A.M.) and (18ck0106436h0001) (T.M.), a grant from the National Center for Child Health and Development (30-1) (D.T.), and a research grant from the Children?s Cancer Association of Japan.
Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/10
Y1 - 2020/10
N2 - The prognosis for infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of hematopoietic stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcome was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial, infants with ALL were stratified into 3 risk groups (low risk [LR], intermediate risk [IR], and high risk [HR]) according to KMT2A status, age, and presence of central nervous system leukemia. Children’s Oncology Group AALL0631 modified chemotherapy with the addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients only. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (n 5 15), IR (n 5 19), or HR (n 5 56) risk groups. The 3-year event-free survival (EFS) rate for patients with KMT2A-r ALL (IR 1 HR) was 66.2% (standard error [SE], 5.6%), and for those with germline KMT2A (KMT2A-g) ALL (LR), the 3-year EFS rate was 93.3% (SE, 6.4%). The 3-year EFS rate was 94.4% (SE, 5.4%) for IR patients and 56.6% (SE, 6.8%) for HR patients. In multivariable analysis, female sex and MRD ‡0.01% at the end of early consolidation were significant factors for poor prognosis. Risk stratification and introduction of intensive chemotherapy in this study were effective and were able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.
AB - The prognosis for infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of hematopoietic stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcome was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial, infants with ALL were stratified into 3 risk groups (low risk [LR], intermediate risk [IR], and high risk [HR]) according to KMT2A status, age, and presence of central nervous system leukemia. Children’s Oncology Group AALL0631 modified chemotherapy with the addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients only. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (n 5 15), IR (n 5 19), or HR (n 5 56) risk groups. The 3-year event-free survival (EFS) rate for patients with KMT2A-r ALL (IR 1 HR) was 66.2% (standard error [SE], 5.6%), and for those with germline KMT2A (KMT2A-g) ALL (LR), the 3-year EFS rate was 93.3% (SE, 6.4%). The 3-year EFS rate was 94.4% (SE, 5.4%) for IR patients and 56.6% (SE, 6.8%) for HR patients. In multivariable analysis, female sex and MRD ‡0.01% at the end of early consolidation were significant factors for poor prognosis. Risk stratification and introduction of intensive chemotherapy in this study were effective and were able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.
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U2 - 10.1182/BLOOD.2019004741
DO - 10.1182/BLOOD.2019004741
M3 - Article
C2 - 32845001
AN - SCOPUS:85093539325
VL - 136
SP - 1813
EP - 1823
JO - Blood
JF - Blood
SN - 0006-4971
IS - 16
ER -