Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group (TCCSG) Study L04-16

Takahashi, Hiroyuki; Kajiwara, Ryosuke; Kato, Motohiro; Hasegawa, Daisuke; Tomizawa, Daisuke; Noguchi, Yasushi; Koike, Kenichi; Toyama, Daisuke; Yabe, Hiromasa; Kajiwara, Michiko; Fujimura, Junya; Sotomatsu, Manabu; Ota, Setsuo; Maeda, Miho; Goto, Hiroaki; Kato, Yoko; Mori, Tetsuya; Inukai, Takeshi; Shimada, Hideaki; Fukushima, Keitaro; Ogawa, Chitose; Makimoto, Atsushi; Fukushima, Takashi; Ohki, Kentaro; Koh, Katsuyoshi; Kiyokawa, Nobutaka; Manabe, Atsushi; Ohara, Akira

doi:10.1007/s12185-018-2440-4

Cited by 48 publications

(48 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reported rates of CNS-2 and CNS-3 leukemia in children have ranged from 5.4% to 32.2% and from 1.6% to 4.7%, respectively, 5,6 with EFS and OS rates for patients with CNS disease ranging from 43% to 86% and from 64% to 95%, respectively, depending on whether infants or patients with a CNS-2 status or TLP with blasts were enrolled. 5,6,8,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] In the TPOG-ALL-2002 study, the incidence rates for CNS-2 and CNS-3 involvement were similar to those cited previously and did not change significantly from one treatment era to the next. Treatment outcomes in patients with a CNS-2 or CNS-3 status were also comparable to results obtained in contemporary trials that adopted the same definition of CNS status.…”

Section: Discussionmentioning

confidence: 55%

Treatment of childhood acute lymphoblastic leukemia with delayed first intrathecal therapy and omission of prophylactic cranial irradiation: Results of the TPOG‐ALL‐2002 study

Yeh

Liang

Hou

et al. 2018

Cancer

View full text Add to dashboard Cite

Background To eliminate cranial irradiation (CrRT)–related sequelae and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, the Taiwan Pediatric Oncology Group (TPOG) introduced a modified central nervous system (CNS)–directed regimen characterized by delayed triple intrathecal therapy (TIT) and the omission of CrRT for all children with newly diagnosed acute lymphoblastic leukemia (ALL). Methods This study compared the treatment outcomes of patients overall and patients with a non–CNS‐1 status (CNS‐2, CNS‐3, or TLP with blasts) in 2 treatment eras, one before and another after the revision of the TPOG‐ALL‐2002 protocol by the introduction of the modification (era 1 [2002‐2008] with CrRT and era 2 [2009‐2012] with delayed first TIT and no CrRT). Results There were no statistically significant differences in major outcomes between the 903 patients treated in era 1 and the 444 patients treated in era 2: the 5‐year event‐free survival (EFS) rates were 75.7% ± 1.4% and 72.1% ± 2.4%, respectively (P = .260), and the cumulative risks of isolated CNS relapse were 4.0% ± 0.7% and 4.1% ± 1.0%, respectively (P = .960). There were also no differences between non–CNS‐1 patients treated in era 1 (n = 76) and era 2 (n =28): the 5‐year EFS rates were 52.3% ± 5.8% and 62.9% ± 9.4%, respectively (P = .199), and the cumulative risks of isolated CNS relapse were 6.3% ± 3.1% and 3.6% ± 3.5%, respectively (P = .639). Notably, TLP with blasts was completely eliminated after the first TIT was delayed in era 2. Conclusions The delay of the first TIT until the clearance of circulating blasts and the total omission of CrRT did not compromise survival or CNS control in patients with childhood ALL, including those with a non–CNS‐1 status.

show abstract

Section: Discussionmentioning

confidence: 55%

Treatment of childhood acute lymphoblastic leukemia with delayed first intrathecal therapy and omission of prophylactic cranial irradiation: Results of the TPOG‐ALL‐2002 study

Yeh

Liang

Hou

et al. 2018

Cancer

View full text Add to dashboard Cite

show abstract

“…We prospectively evaluated MRD levels in a t(17;19)‐ALL case, treated with a high risk (HR) regimen in the TCCSG L04‐16 study, using real‐time RT‐PCR targeting of TCF3‐HLF (Figure ). Higher levels of TCF3‐HLF chimeric mRNA were continuously detected during intensified induction therapy consisting of Pred, VCR, DNR, l ‐Asp, and CPM.…”

Section: Resultsmentioning

confidence: 99%

“…The patients were enrolled in Tokyo Children's Cancer Study Group (TCCSG) L04‐16 study . Minimal residual disease MRD was tested for by using bone marrow aspirates obtained at diagnosis and on days 15, 29, and 43.…”

Section: Methodsmentioning

confidence: 99%

“…The patients were enrolled in Tokyo Children's Cancer Study Group (TCCSG) L04-16 study. 18 Minimal residual disease MRD was tested for by using bone marrow aspirates obtained at diagnosis and on days 15, 29, and 43. Real-time polymerase chain reaction (PCR) analysis for TCF3-PBX1 was performed using sense (5′-CCAGCCTCATGCACAACCA-3) and antisense (5′-GGGCTCCTCGGATACTCAAAA-3′) primers with probe (5′-FAM-CCCTCCCTGACCTGTCTCGGCC-TAMRA-3′), as previously described.…”

Section: Minimal Residual Disease Analysesmentioning

confidence: 99%

See 1 more Smart Citation

Resistance of t(17;19)‐acute lymphoblastic leukemia cell lines to multiagents in induction therapy

et al. 2019

Self Cite

View full text Add to dashboard Cite

t(17;19)(q21‐q22;p13), responsible for TCF3‐HLF fusion, is a rare translocation in childhood B‐cell precursor acute lymphoblastic leukemia(BCP‐ALL). t(1;19)(q23;p13), producing TCF3‐PBX1 fusion, is a common translocation in childhood BCP‐ALL. Prognosis of t(17;19)‐ALL is extremely poor, while that of t(1;19)‐ALL has recently improved dramatically in intensified chemotherapy. In this study, TCF3‐HLF mRNA was detectable at a high level during induction therapy in a newly diagnosed t(17;19)‐ALL case, while TCF3‐PBX1 mRNA was undetectable at the end of induction therapy in most newly diagnosed t(1;19)‐ALL cases. Using 4 t(17;19)‐ALL and 16 t(1;19)‐ALL cell lines, drug response profiling was analyzed. t(17;19)‐ALL cell lines were found to be significantly more resistant to vincristine (VCR), daunorubicin (DNR), and prednisolone (Pred) than t(1;19)‐ALL cell lines. Sensitivities to three (Pred, VCR, and l ‐asparaginase [ l ‐Asp]), four (Pred, VCR, l ‐Asp, and DNR) and five (Pred, VCR, l ‐Asp, DNR, and cyclophosphamide) agents, widely used in induction therapy, were significantly poorer for t(17;19)‐ALL cell lines than for t(1;19)‐ALL cell lines. Consistent with poor responses to VCR and DNR, gene and protein expression levels of P‐glycoprotein (P‐gp) were higher in t(17;19)‐ALL cell lines than in t(1;19)‐ALL cell lines. Inhibitors for P‐gp sensitized P‐gp‐positive t(17;19)‐ALL cell lines to VCR and DNR. Knockout of P‐gp by CRISPRCas9 overcame resistance to VCR and DNR in the P‐gp‐positive t(17;19)‐ALL cell line. A combination of cyclosporine A with DNR prolonged survival of NSG mice inoculated with P‐gp‐positive t(17;19)‐ALL cell line. These findings indicate involvement of P‐gp in resistance to VCR and DNR in Pgp positive t(17;19)‐ALL cell lines. In all four t(17;19)‐ALL cell lines, RAS pathway mutation was detected. Furthermore, among 16 t(1;19)‐ALL cell lines, multiagent resistance was usually observed in the cell lines with RAS pathway mutation in comparison to those without it, suggesting at least a partial involvement of RAS pathway mutation in multiagent resistance of t(17;19)‐ALL.

show abstract

“…Complete remission (CR) was achieved on day 33 without serious complications (Figure ). The patient was administered postremission chemotherapy adopted from the low‐risk regimen of the Tokyo Children's Cancer Study Group L04‐16 protocol with dasatinib . Minimal residual disease (MRD) levels detected based on immunoglobulin and T‐cell receptor gene rearrangements were 6 × 10 –4 on day 33 and became undetectable on day 95.…”

mentioning

confidence: 99%

Dasatinib and low‐intensity chemotherapy for Philadelphia chromosome‐positive acute lymphoblastic leukemia in a child with Down syndrome

Hirabayashi

Hasegawa

Yamamoto

et al. 2019

Pediatric Blood & Cancer

Self Cite

View full text Add to dashboard Cite

Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group (TCCSG) Study L04-16

Cited by 48 publications

References 30 publications

Treatment of childhood acute lymphoblastic leukemia with delayed first intrathecal therapy and omission of prophylactic cranial irradiation: Results of the TPOG‐ALL‐2002 study

Treatment of childhood acute lymphoblastic leukemia with delayed first intrathecal therapy and omission of prophylactic cranial irradiation: Results of the TPOG‐ALL‐2002 study

Resistance of t(17;19)‐acute lymphoblastic leukemia cell lines to multiagents in induction therapy

Dasatinib and low‐intensity chemotherapy for Philadelphia chromosome‐positive acute lymphoblastic leukemia in a child with Down syndrome

Contact Info

Product

Resources

About