Outcome of 136 Children with Advanced Lymphoblastic Lymphoma Receiving an BFM-Type Therapy with Intensified Maintenance: A Report from the Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 Study
Authors: Sunami Shosuke , Sekimizu Masahiro , Takimoto Tetsuya , Mori Tetsuya , Mitsui Tetsuo , Fukano Reiji , Mori Takeshi , Kikuta Atsushi , Katsuyoshi Koh , Imamura Toshihiko , Saito Akiko Moriya , Watanabe Tomoyuki , Ohshima Kouichi , Fujimoto Junichiro , Nakazawa Atsuko , Kobayashi Ryoji , Horibe Keizo , Tsurusawa Masahito 
Published: October 2019

Abstract
BACKGROUND: Lymphoblastic lymphoma (LBL) accounts for 30% of childhood non Hodgkin’s lymphoma in Japan. From European and North American groups, favorable results have been reported, using treatment strategies for acute lymphoblastic leukemia, over 80% of event free survival rate even in advanced LBL. However there were few data on Japanese or Asian patients with LBL. Here we report final outcome of first nation-wide prospective study over one hundred cases with advanced childhood LBL from Japan.
PATIENTS & METHOD: Patients with stage 3 or 4 LBL received for 9 weeks induction phase, which consisted of 7 drugs and triple IT , followed by three courses of high dose MTX(5g/m2). After high dose MTX, re-induction, early maintenance, and late maintenance phase were administered. With an attempt to intensify maintenance therapy,early maintenance was consisted by two cycles of four courses of six drugs(MTX, PSL,VCR, L-ASP, 6MP, THP#) and late maintenance was five cycles of five drugs(MTX, PSL,VCR, 6MP,AraC). We omitted local radiotherapy including prophylactic cranial radiotherapy except patient with initial central nervous system (CNS) disease. The total duration of the treatment was 24 month.
RESULTS: From November 2004 to October 2010, 154 children with newly diagnosed advanced stage LBL were entered in this study. A total of 136 cases were eligible. Ages ranged from four month to 15 years, with a median of 9.07 years. Of the 136 patients, 36 were girls and 100 were boys. The distribution of clinical stage 3 and stage 4 was 82 and 54 patients respectively. 94 patients had primary mediastinal disease. 41 patients had BM disease, 31 patients had CNS disease and 8 patients had BM and CNS disease. 104 patients (76.5%) had precursor T LBL (T-LBL), 31 patients (22.8%) had precursor B LBL (B-LBL), onepatient (0.7%) had bi phenotype LBL. The follow-up time ranged from 2.8 to 94 months, with a median 58 months. For the 136 patients analyzed in this study, 5-year OS was 82.9% and 5-year EFS was 77.9%. There was no significant difference in outcome by gender (5-year EFS, male 78.2% vs. female 73.0%), or by immunophenotype (5-year EFS, B-LBL 80.7% vs. T-LBL 76.9%). Of note, the 5-year EFS for stage 3 T-LBL patients were worse than that of stage 4 T-LBL patients (70.6% vs. 88.9%, P=0.031). There were also significant difference in 5-year EFS for T-LBL patients who achieved CR and CRu at end of induction, 86.9%, and 69.7% (P=0.034), respectively.Most events were observed as mediastinum enlargement before initiation of intensified maintenance therapy.
CONCLUSIONS: Our firstnationwide study provided about 80% cure rate with only one case of toxic death in childhood advanced LBL. However, our intensified maintenance therapy could not improve survival outcome. Our result also emphasize the significant difference between T-LBL stage 3 and stage 4 and might suggest the difference in ethnicity for the composition of biological subgroup in T-LBL.
THP: Pirarubicin

Disclosures
No relevant conflicts of interest to declare.