Efficacy evaluation of the 2017 protocol by the China Net Childhood Lymphoma in treating early T cell precursors-lymphoblastic lymphoma in pediatric patients

Efficacy evaluation of the 2017 protocol by the China Net Childhood Lymphoma in treating early T cell precursors-lymphoblastic lymphoma in pediatric patients | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 21 July 2025 V1 Latest version Share on Efficacy evaluation of the 2017 protocol by the China Net Childhood Lymphoma in treating early T cell precursors-lymphoblastic lymphoma in pediatric patients Authors : Zhizhuo Huang 0000-0003-4376-5399 , Ling Jin , Wei Liu , Sun Lirong , Baoxi Zhang , Shuquan Zhuang , Xiaojun Yuan , Yueping Jia [email protected] , and Yonghong Zhang Authors Info & Affiliations https://doi.org/10.22541/au.175308488.84032946/v1 216 views 107 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract To analyze the clinical features of ETP-LBL in pediatric patients and to summarize the efficacy evaluation of the 2017 protocol by the CNCL NHL 2017-LBL for ETP-LBL. Methods The clinical data of 19 children with ETP-LBL admitted to CNCL from May 2017 to August 2023 were retrospectively collected. Results The median age of onset was 10 years old (4.5-13 years old), including 16 males (84.2%) and 3 females (15.8%). All patients were in stage IV and were treated with high-risk chemotherapy regimen. 11 of them (57.9%) underwent HSCT. The proportion of leukemia stage in the HSCT group was significantly higher than that in the chemotherapy group (72.7% vs. 25.0%), and the central status was CNS2/3 in the HSCT group (100% vs. 50%).The 3-year OS and EFS were (93.8±0.61) % and (88.2±0.78) %, respectively. Conclusion More than 50% of pediatric ETP-LBL patients received HSCT. The long-term survival rates were similar. Efficacy evaluation of the 2017 protocol by the China Net Childhood Lymphoma in treating early T cell precursors-lymphoblastic lymphoma in pediatric patients Huang Zhizhuo 1 , Jin Ling 2 , Liu Wei 3 ,Sun Lirong 4 , Zhang Baoxi 5 , Zhuang Shuquan 6 , Yuan Xiaojun 7 , Jia Yueping 1 , Zhang Yonghong 8 1 Department of Pediatrics, Peking University People′s Hospital, Beijing 100044, China; 2 Medical Oncology Department, Pediatric Oncology Center, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing Key Laboratory of Pediatric Hematology Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China; 3 Department of Hematology & Oncology, Zhengzhou Children′s Hospital, Zhengzhou 450018, China; 4 Department of Pediatric Hematology & Oncology, the Affiliated Hospital of Qingdao University, Qingdao 266003, China; 5 Department of Pediatrics, Second Hospital of Hebei Medical University, Shijiazhuang 050004, China; 6 Department of Pediatrics, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou 362002, China; 7 Department of Pediatric Hematology/Oncology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; 8 Department of Pediatric Lymphoma, Beijing GoBroad Boren Hospital, Beijing 100070, China Huang Zhizhuo and Jin Ling contributed equally to this article. Corresponding authors: Jia Yueping, Email：jyp2931@vip. sina. com； Zhang Yonghong , Email： [email protected] Abstract: To analyze the clinical features of ETP-LBL in pediatric patients and to summarize the efficacy evaluation of the 2017 protocol by the CNCL NHL 2017-LBL for ETP-LBL. Methods The clinical data of 19 children with ETP-LBL admitted to CNCL from May 2017 to August 2023 were retrospectively collected. Results The median age of onset was 10 years old (4.5-13 years old), including 16 males (84.2%) and 3 females (15.8%). All patients were in stage IV and were treated with high-risk chemotherapy regimen. 11 of them (57.9%) underwent HSCT. The proportion of leukemia stage in the HSCT group was significantly higher than that in the chemotherapy group (72.7% vs. 25.0%), and the central status was CNS2/3 in the HSCT group (100% vs. 50%).The 3-year OS and EFS were (93.8±0.61) % and (88.2±0.78) %, respectively. Conclusion More than 50% of pediatric ETP-LBL patients received HSCT. The long-term survival rates were similar. Key words: early T cell precursors-lymphoblastic lymphoma, pediatric patients, chemotherapy, hematopoietic stem cell transplantation, prognosis Jin ling [email protected] Liu wei [email protected] Sunlirong [email protected] Zhangbaoxi [email protected] Yuanxiaojun [email protected] Zhuangshuquan [email protected] Introduction In 2009, Coustan-Smith et al. first proposed the concept of early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL). The 2016 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues identified ETP-ALL/LBL as a distinct immunophenotype separate from T-LBL. ETP-ALL/LBL is a highly aggressive subtype of T-ALL with transcriptional and phenotypic profiles resembling early T-cell progenitors, accounting for approximately 12%–13% of pediatric T-ALL and 4% of T-LBL[1]. It exhibits gene expression patterns similar to hematopoietic and myeloid progenitors, with increased rates of induction failure, increased frequency of end of consolidation (EOC) minimal residual disease (MRD), higher relapse rate, and generally poor prognosis. Studies in adult ETP-ALL patients showed it is a high-risk subgroup of T-ALL/LBL[2]. However, the prognosis of pediatric ETP-ALL remains controversial, and data on pediatric ETP-LBL are scarce. This study retrospectively analyzed the clinical characteristics and treatment outcomes of pediatric ETP-LBL treated by the China Net Childhood Lymphoma (CNCL) from May 2017 to August 2023, aiming to improve understanding of this subtype, enhance treatment strategies, and optimize prognosis. I. Subjects This retrospective study included 19 newly diagnosed pediatric patients (aged ≤16 years) with ETP-LBL who were treated by CNCL between May 2017 and August 2023. All patients received standardized chemotherapy and follow-up according to the CNCL-NHL-2017-LBL protocol. The study was approved by the Ethics Committee of Beijing Children’s Hospital (IEC-C-008-A08-V.05.1), and written informed consent was obtained from guardians and patients (≥8 years old). A total of 7 hospitals participated in this study, ranked by the number of contributed cases as follows: 1. Beijing Children’s Hospital, Capital Medical University 2. Peking University People’s Hospital 3. Zhengzhou Children’s Hospital 4. Children’s Medical Center, Affiliated Hospital of Qingdao University 5. Second Hospital of Hebei Medical University 6. First Hospital of Quanzhou, Affiliated to Fujian Medical University 7. Xinhua Hospital, Shanghai Jiao Tong University School of Medicine II. Methods 1. Data Collection Clinical data were retrieved from hospital electronic medical records and the CNCL database, including: demographic characteristics: age at onset and sex, disease course and initial symptoms, tumor size and involved sites, white blood cell count, serum lactate dehydrogenase (LDH) levels, clinical staging and risk stratification, cytogenetic/molecular biological features, treatment regimens, therapeutic responses, and prognostic outcomes. 2. Diagnosis and Staging Diagnosis was confirmed based on the clinical presentation, histopathological examination of tumor tissue, immunohistochemistry, cytogenetic, and molecular biological testing. All pathological specimens were reviewed by the CNCL Pathology Center, with consensus from at least two expert pathologists required for definitive diagnosis of ETP-LBL, in accordance with the 2021 diagnostic scoring criteria [3]. Clinical staging was performed using the St. Jude staging system [4], incorporating: • Peripheral blood tests • Bone marrow aspirate/biopsy • Cerebrospinal fluid (CSF) analysis • Imaging studies (X-ray, ultrasonography, CT, MRI, PET-CT) CNS Status Classification was included CNS1, CNS2 and CNS3. • CNS1 : All of the following: (1) No tumor cells in CSF (2) No clinical CNS abnormalities (3) No CNS abnormalities on imaging (CT/MRI) • CNS2 : Any of the following: (1) Non-traumatic lumbar puncture (RBC:WBC ≤100:1) with CSF WBC ≤5/µL and definitive tumor cells (2) Traumatic lumbar puncture (RBC:WBC >100:1) with definitive tumor cells in CSF (3) Traumatic lumbar puncture with bloody CSF (regardless of tumor cells) and initial WBC >50×10⁹/L (4) CNS-adjacent involvement (e.g., skull, sinuses, orbit without dural penetration) or vertebral/paraspinal lesions without neurological symptoms and no CNS mass/normal CSF (5) T-cell phenotype with high tumor burden (defined as: tumor diameter ≥10 cm; ≥2 lesions >5 cm; involvement of >4 organs; or WBC ≥50×10⁹/L) • CNS3 : Any of the following: (1) CSF WBC >5/µL with tumor cell predominance (RBC:WBC ≤100:1) or tumor cell percentage exceeding peripheral blasts (2) Cranial nerve palsy (even without CSF tumor cells or imaging abnormalities) (3) Brain/spinal cord or meningeal lesions on CT/MRI (4) Vertebral/paraspinal lesions causing neurological deficits (e.g., urinary dysfunction, motor impairment) 3. Risk Stratification and Treatment All patients initially received intermediate-risk chemotherapy. Escalation to high-risk chemotherapy was determined by: 1. Prednisone response (Day 8) : Peripheral blasts >1×10⁹/L 2. Induction therapy (Day 15) : Bone marrow blasts >25% 3. End of induction therapy (EOI, Day 33): a. Tumor residue >25% or marrow blasts >5% ; b. Bone marrow MRD ≥10⁻² ; c. Persistent CSF blasts (after triple intrathecal therapy) 4. EOC : Residual tumor lesions or bone marrow MRD ≥10⁻³ 5. Adverse genetic features : t(9;22)/BCR-ABL or t(4;11)/MLL-AF4 According to the modified CNCL-NHL 2017-LBL regimen based on the BFM-90 protocol, risk-stratified chemotherapy involves maintenance therapy consisting of 8 cycles, with each cycle lasting 8 weeks (see Figure 1 for details). Indications for Hematopoietic Stem Cell Transplantation (HSCT): 1. EOI: No response (NR) in bone marrow evaluation or MRD ≥5%, tumor shrinkage <25% or disease progression. 2. EOC: Bone marrow MRD ≥0.1%, persistent or progressive residual tumor lesions. 3. Post-High-Risk Phase II Assessment: Bone marrow MRD ≥0.01% or residual tumor lesions. 4. Parental Preference: If the child’s parents opt for transplantation. 5. High-Risk Molecular Abnormalities: Such as SET::CAN fusion , KMT2A rearrangements , etc. 6. Disease Progression or Relapse at Any Stage. 4. Follow-Up Protocol Definition of Events were included disease progression during treatment, relapse after achieving remission, development of a second malignancy, death from any cause, treatment discontinuation/abandonment. From the start of treatment until five years later, follow-up was conducted through outpatient visits or phone calls. The follow-up period ended on December 31, 2023. Ⅲ . Statistical methods Statistical analysis was performed using SPSS 23.0 software. Measurement data were expressed as M (Q1, Q3), and count data were expressed as cases (%). The t-test method was used for the comparison between groups of data conforming to the normal distribution, and the rank sum test method was used for the comparison between groups of data not conforming to the normal distribution. The comparison between groups of count data was conducted using the χ2 test or Fisher’s exact probability method. Survival analysis was performed using the Kaplan-Meier method. The comparison of survival rates between groups was conducted using the Log-rank test. Univariate analysis was performed using Cox regression, and factors with statistical significance were screened out for multivariate analysis. A statistically significant difference was considered when bilateral P < 0.05. Results Clinical Characteristics The median age of onset was 10 years (range: 4.5–13 years), including 16 males (84.2%) and 3 females (15.8%), with a male-to-female ratio of 5.3:1. The median disease course was 1 month (0.2-5 months). The median follow-up time was 46.2 months (8.3-66.8 months). A total of 505 cases of T-LBL were enrolled in CNCL, and ETP-LBL accounted for 3.76% of T-LBL during the same period. All cases were stage Ⅳ, with 10 cases (52.6%) in the leukemia phase. CNS status was observed in 4 cases (21.1%) for CNS1, 14 cases (73.7%, because of T-LBL with high tumor burden) for CNS2, and 1 case (5.2%, tumor cells were detected in CSF) for CNS3. The initial diagnosis symptoms were respectively: superficial lymphadenopathy (11/19), cough or wheezing (8/19). There was no hyperleukocytosis (WBC≥50×10 9 /L) at the onset of the disease. The others symptoms such as fever, mediastinal involvement, huge tumor mass, and involvement >4 organs accounted for 26.3%, 73.7%, 42.1%, 68.4%, and 42.1% of elevated LDH respectively. None of the reproductive systems were involved (details for Table 1). The specimens with myeloid antigen expression were mainly bone marrow immunotyping specimens (15/19) and lymph node or mediastinal pathological specimens (4/19). The myeloid antigen positive expressions included CD13 (8/19), CD33 (15/19), and CD117 (7/19). There was no expression of MPO. There were 10 cases with two or more myeloid antigen expressions, including 5 cases of CD33+CD117, 4 cases of CD13+CD33, and 1 case of CD13+CD33+CD117. 7 cases with fusion genes were detected in the bone marrow(3 cases of SET::CAN, 1 case of KMT2A::AF6, 1 case of HOXA10::IGH, 1 case of TRA/D::MYC, 1 case of HOXB::IGH. There were 10 cases with normal karyotypes of bone marrow chromosomes. Treatment Response All patients received high-risk chemotherapy, with 11 cases (57.9%) undergoing HSCT. The transplantation indications of them were due to EOC residual tumor lesions in 6 cases, EOC bone marrow MRD > 0.1% in 1 case, high-risk fusion genes in 2 cases, molecular relapse in 1 case, EOI bone marrow MRD > 1% and parental preference in 1 case. The HSCT group had higher tumor burden (leukemia phase: 72.7% vs. 25.0%; CNS2 and CNS3: 100% vs. 50%). The residual rate of EOC tumor lesions in the HSCT group was significantly higher than the positive rate of bone marrow MRD (54.5% vs. 9.1%). No significant differences were observed in MRD or residual tumor lesions between the two groups after prednisone pretreatment, 15 days of induction chemotherapy, EOI, EOC, and the end of one round of high-risk regimens. In the chemotherapy group, both MRD and residual tumor lesions were negative at the end of two rounds of high-risk regimens and before maintenance chemotherapy. Prognosis The 3-year OS and EFS rates were 93.8% and 88.2%, respectively, with no significant differences between the HSCT and chemotherapy groups (3-year OS 90.0% vs. 100%, p=0.439; 3-year EFS 90.0% vs. 85.7%, p=0.757; Figure 2). One case (5.0%) in the HSCT group died of post-transplant pulmonary infection, and the rest survived until the end of follow-up. One patient in the chemotherapy group required surgical intervention (ileocecal lesion resection + extensive adhesiolysis + abdominal drainage) due to intestinal obstruction and infection, leading to a 4-month chemotherapy interruption. The postoperative intestinal pathology ruled out tumor evidence. Factors Affecting Prognosis Both univariate and multivariate analyses indicated that tumor stage, huge tumor lesion, mediastinal involvement, elevated LDH, CNS status, chromosomal karyotype, prednisone pretreatment sensitivity, bone marrow MRD and tumor lesion residue of EOI, EOC, after one round of high-risk regimens, and chemotherapy/HSCT had no effect on OS and EFS. Discussion ETP-ALL/LBL is a highly aggressive T-cell malignancy with distinct transcriptomic and phenotypic features. In adults, ETP accounts for 20-30% of T-ALL/LBL cases, while in pediatric T-ALL it represents 12-13%, with pediatric ETP-LBL being even rarer. Although there is abundant literature on pediatric ETP-ALL and ETP-ALL/LBL, dedicated studies focusing solely on pediatric ETP-LBL remain scarce, leaving its clinical characteristics, genomic profile, treatment strategies, and prognosis incompletely understood. The COG AALL0434 study (2021) [1] reported 9 pediatric ETP-LBL cases, constituting approximately 4% of pediatric T-LBL cases at the time, with a median age of onset at 10.7 years and a male-to-female ratio of 1.25:1. A Chinese retrospective study [5] involving 128 adolescent and adult T-ALL/LBL patients found that ETP-ALL/LBL accounted for 47.6% of cases, among which only 8 (6%) were ETP-LBL, predominantly male. Data from our collaborative group indicate that pediatric ETP-LBL has an incidence of 3.76%, primarily affecting school-aged children with a male predominance, consistent with previous reports. ETP tumor cells originate from the earliest T-cell precursors in the thymus and typically lack CD1a and CD8 expression, exhibit weak or negative CD5, and express one or more myeloid markers (CD13, CD33, CD117) or stem cell markers (CD34, HLA-DR) in >25% of cells, demonstrating stem-cell and myeloid-like immunophenotypic and genetic characteristics [6]. In our study, myeloid antigen expression in ETP-LBL was most commonly observed for CD33 and CD13, with approximately half of the patients expressing two or more myeloid markers. Prior studies [5,7] suggest that in T-ALL, CD13 and CD33 expression correlates with lower OS and complete remission (CR1) rates, which aligns with the generally poor prognosis of the ETP phenotype. However, CD33 positivity may hold potential for targeted therapy in ETP-ALL/LBL. Genomically, ETP-ALL/LBL exhibits a distinct mutation profile compared to non-ETP-ALL/LBL, with frequent alterations in genes involved in normal hematopoietic development, RAS signaling, DNA methylation, and histone modification [7], resembling the mutational landscape of acute myeloid leukemia (AML). However, the prognostic implications of these mutations remain unclear. Reported ETP-associated mutations include DNMT3A, IDH1/2, FLT3, RAS pathway genes, and JAK-STAT/IL-7R signaling activators, often accompanied by biallelic TCRγ deletion and recurrent chromosomal losses at 12p and 1p, while NOTCH1/FBXW7 mutations and 9p (CDKN2A/B) deletions are less common [1]. In our cohort, some patients underwent genetic testing, revealing NOTCH1 mutations as the most prevalent, alongside IKZF1, WT1, IL7R, and KDM6A mutations. Approximately one-third of cases harbored one of five fusion genes (SET::CAN, KMT2A::AF6, HOXA10::IGH, TRA/D::MYC, HOXB::IGH), which are not typical of T-LBL. Recent advances have identified B-cell lymphoma-2 (BCL-2) inhibitors as promising targeted therapies for ETP-ALL/LBL [8-9], with combination chemotherapy showing improved response rates and outcomes. However, routine immunophenotyping does not typically assess BCL2 expression, suggesting a need for its inclusion in future diagnostic workups to guide precision therapy. A recent proteomics study [10] proposed risk stratification for pediatric and adult ETP-ALL, revealing age-specific protein expression patterns that support distinct origins for most pediatric and adult T-ALL cases, while overlapping profiles in some patients indicate shared pathophysiology, offering new avenues for molecular prognostication. Clinically, adult ETP-ALL patients tend to be older, present with higher blast counts and lower white blood cell levels, and exhibit poorer responses to induction chemotherapy, lower remission rates, and worse long-term survival compared to non-ETP-ALL [2,3], though clinical staging, IPI scores, LDH levels, and mediastinal involvement rates show no difference. Pediatric ETP-ALL studies [11-12] report lower rates of hyperleukocytosis, mediastinal masses in 25% of cases, and CNS involvement in ~12%. Our pediatric ETP-LBL cohort showed no hyperleukocytosis, ~5% CNS leukemia, and mediastinal involvement in ~75% of cases—higher than in ETP-ALL, possibly reflecting the greater propensity of ETP-LBL for mediastinal disease. Within the HSCT group, leukemia-phase presentation and CNS2 and CNS3 status were more frequent than in the chemotherapy group, suggesting higher tumor burden, though other clinical features were comparable. No standardized chemotherapy regimen exists for ETP-ALL/LBL, with current approaches largely adapted from T-ALL protocols. Adult patients respond poorly to intensive chemotherapy, experiencing high rates of induction failure and relapse, making ETP a marker of adverse prognosis. Allogeneic HSCT post-remission may improve outcomes [11,13]. Pediatric data, however, are conflicting: while early studies suggested inferior survival in ETP-ALL, recent trials report comparable OS and EFS between ETP and non-ETP subtypes. The COG AALL0434 trial [14] (2009-2014, n=1256 pediatric/adolescent/young adult T-ALL/LBL patients) found that while ETP cases (11.5%) had higher induction failure (6.2% vs. 1.2%), EOI-MRD ≥1%, and MRD ≥0.1% rates than non-ETP, their 5-year OS (80.4% vs. 85.3%) and EFS (86.8% vs. 90%) were similar. Multivariate analysis identified hyperleukocytosis, EOI-MRD ≥0.1%, and EOC-MRD ≥0.01% as adverse prognostic factors in T-ALL, but not ETP status itself. Among ETP patients, only EOI-MRD ≥10% predicted worse outcomes, while EOI-MRD ≥0.1% and EOC-MRD ≥0.01% did not, implying that induction failure outweighs MRD positivity in prognostic impact. The UKALL2003 study [15] likewise found no significant difference in 5-year EFS (76.7% vs. 84.6%) or OS (82.4% vs. 90.9%) between 35 pediatric ETP-ALL and non-ETP cases. Given that ETP often exhibits steroid resistance leading to high MRD, early intensification with high-risk regimens may mitigate the negative impact of chemoresistance. In our study, all ETP-LBL patients received high-risk chemotherapy, achieving 3-year OS and EFS rates of 93.8% and 88.2%, respectively—superior to non-ETP T-LBL outcomes (84% and 78%, unpublished data), possibly attributable to the higher HSCT rate (57.9%) in our cohort compared to international reports. Notably, no differences in EOI/EOC bone marrow MRD or residual disease were observed between transplanted and chemotherapy-only groups, with comparable 3-year OS and EFS, suggesting that HSCT may not confer additional survival benefit. Whether intensive chemotherapy or novel targeted therapies could replace transplantation in ETP-LBL warrants further investigation. Limitations: The small sample size and incomplete genetic profiling highlight the need for larger, multicenter studies with extended follow-up. Conclusion: Over half of pediatric ETP-LBL patients underwent HSCT, yet survival outcomes were comparable to chemotherapy alone. Further studies are needed to validate whether intensive chemotherapy or novel targeted therapies can reduce reliance on HSCT. References 1. Xu X, Paxton CN, Hayashi RJ, et al. Genomic and clinical characterization of early T-cell precursor lymphoblastic lymphoma. Blood Adv. 2021; 27, 5(14): 2890-2900. 2. Jain N., Lamb A. V., O’Brien S., et al. Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype. Blood. 2016;127(15): 1863–1869. 3. Sin C-f, Man P-hM. Early T Cell Precursor Acute Lymphoblastic Leukemia: Diagnosis, Updates in Molecular Pathogenesis, Management, and Novel Therapies. Front. Oncol. 2021; 11:750789. 4. Murphy SB. Classification, staging and end results of treatment of childhood non‑Hodgkin′s lymphomas: dissimilarities from lymphomas in adults. Semin Oncol. 1980; 7(3): 332‑339. 5. Liao HY, Sun ZY, Wang YX, et al. Outcome of 126 adolescent and adult T-cell acute leukemia/lymphoma patients and the prognostic significance of early T-cell precursor leukemia subtype. Zhonghua Xue Ye Xue Za Zhi. 2019; 40(7): 561-567. 6. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 2016; 127(20): 2391-2405. 7. Marks DI, Paietta EM, Moorman AV, et al. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood, 2009; 114(25): 5136-5145. 8. Wan CL, Zou JY, Qiao M, et al. Venetoclax combined with azacitidine as an effective and safe salvage regimen for relapsed or refractory T-cell acute lymphoblastic leukemia: a case series. Leuk Lymphoma, 2021; 62(13): 3300–3303. 9. Arora S, et al. Venetoclax with chemotherapy in relapse/refractory early T-cell precursor acute lymphoblastic leukemia. Leuk Lymphoma, 2021; 62(9): 2292–2294. 10. Hoff FW, Sriraja L, Qiu Y, et al. The Proteomics of T-Cell and Early T-Cell Precursor (ETP) Acute Lymphocytic Leukemia: Prognostic Patterns in Adult and Pediatric-ETP ALL. Cancers(Basel), 2024; 16(24): 4241. 11. B. Burkhardt and M. L. Hermiston, Lymphoblastic lymphoma in children and adolescents: review of current challenges and future opportunities. British Journal of Haematology, 2019; 185(6): 1158–1170. 12. Wood BL, Devidas M, Summers RJ, et al. Prognostic significance of ETP phenotype and minimal residual disease in T-ALL: a Children’s Oncology Group study. Blood, 2023; 142(24): 2069-2078. 13. Liu S, Cui Q, Dai H, et al. Early T-Cell Precursor Acute Lymphoblastic Leukemia and T/Myeloid Mixed Phenotype Acute Leukemia Possess Overlapping Characteristics and Both Benefit From CAG-Like Regimens and Allogeneic Hematopoietic Stem Cell Transplantation. Transplant Cell Ther, 2021; 27(6):481.e1-481.e7. 14. Winter SS, Dunsmore KP, Devidas M, et al. Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children’s Oncology Group AALL0434 Methotrexate Randomization. J Clin Oncol, 2018; 36(29): 2926-2934. 15. Patrick K, Wade R, Goulden N, et al. Outcome for children and young people with Early T-cell precursor acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003. Br J Haematol, 2014; 166(3): 421-424. Supplementary Material File (table 1.pdf) Download 179.00 KB Information & Authors Information Version history V1 Version 1 21 July 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords chemotherapy lymphoblastic lymphoma pediatric hematology/oncology Authors Affiliations Zhizhuo Huang 0000-0003-4376-5399 Peking University People's Hospital View all articles by this author Ling Jin Capital Medical University Key Laboratory of Major Diseases in Children Ministry of Education View all articles by this author Wei Liu Zhengzhou Children's Hospital View all articles by this author Sun Lirong The Affiliated Hospital of Qingdao University View all articles by this author Baoxi Zhang The Second Hospital of Hebei Medical University View all articles by this author Shuquan Zhuang Fujian Medical University Affiliated First Quanzhou Hospital View all articles by this author Xiaojun Yuan Shanghai Jiaotong University School of Medicine Xinhua Hospital View all articles by this author Yueping Jia [email protected] Peking University People's Hospital View all articles by this author Yonghong Zhang Beijing Gobroad Boren Hospital View all articles by this author Metrics & Citations Metrics Article Usage 216 views 107 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Zhizhuo Huang, Ling Jin, Wei Liu, et al. Efficacy evaluation of the 2017 protocol by the China Net Childhood Lymphoma in treating early T cell precursors-lymphoblastic lymphoma in pediatric patients. Authorea . 21 July 2025. DOI: https://doi.org/10.22541/au.175308488.84032946/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.175308488.84032946/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9fecdae55e851640',t:'MTc3OTI5NTk4MA=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();