Intensified pegylated-asparaginase in consolidation therapy improved outcome of allogeneic hematopoietic stem cell transplantation for adult T-cell acute lymphoblastic leukemia

Sep 29, 2026

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Research on the optimal consolidation therapy for adult T-cell acute lymphoblastic leukemia (T-ALL) remains limited, and how to integrate pediatric-inspired chemotherapy with allogeneic hematopoietic stem cell transplantation (SCT) is less addressed. Retrospective analysis indicated that 4 doses of pegylated-asparaginase (PEG-Asp) prior to SCT were optimal for survival. A PEG-Asp-intensified pediatric-inspired regimen (PDT-ALL-2016) was evaluated in a prospective cohort and a retrospective adult regimen cohort. The prospective cohort showed superior survival, and non-truncated PEG-Asp dosing improved outcomes; high-dose pre-SCT PEG-Asp (4–5 doses) was associated with better survival across analyses.

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CategoryHealthcare

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Abstract

Introduction

Methods

Patients and pre-HSCT chemotherapy

Annals of Hematology (2025) 104:6339–6349 [https://doi.org/10.1007/s00277-025-06576-8](https://doi.org/10.1007/s00277-025-06576-8) RESEARCH Intensified pegylated-asparaginase in consolidation therapy improved outcome of allogeneic hematopoietic stem cell transplantation for adult T-cell acute lymphoblastic leukemia Junjie Chen1,2,3 · Jia Li1,2 · Zhixiang Wang1,2,3 · Zicong Huang1,2 · Jieping Lin1,2 · Jiawang Ou1,2 · Xiuli Xu1,2 · Bingqing Tang1,2 · Chenhao Ding1,2 · Zihong Cai1,2 · Ren Lin1,2 · Xuan Li1,2 · Qifa Liu1,2 · Hongsheng Zhou1,2,3 Received: 20 February 2025 / Accepted: 13 August 2025 / Published online: 23 December 2025 © The Author(s) 2025 Abstract Research on the optimal consolidation therapy for adult T-cell acute lymphoblastic leukemia (T-ALL) remains limited, and how to integrate pediatric-inspired chemotherapy with allogeneic hematopoietic stem cell transplantation (SCT) is less addressed. Based on retrospective analysis indicating that 4 doses of pegylated-asparaginase (PEG-Asp) prior to SCT were optimal for survival, we designed a PEG-Asp-intensified pediatric-inspired regimen, PDT-ALL-2016, for adult T-ALL (NCT03564704) . In this protocol, SCT administered following 4 or 5 doses of PEG-Asp. The impact of PEG-Asp on transplantation outcomes was evaluated in two cohorts: the prospective PDT-ALL-2016 cohort (2016.1-2021.12, N= 63) and the retrospective adult regimen cohort (2008.1-2015.12, N= 61). With intensified PEG-Asp consolidation, the prospective cohort exhibited superior survival compared to the retrospective cohort. Furthermore, within the prospective cohort, patients who received non-truncated PEG-Asp demonstrated better survival than those who received a truncated dose. Then, the entire cohort was stratified into high-dose (4–5 doses, N= 45), medium-dose (2–3 doses; N= 33) and low-dose (0–1 doses; N= 46) groups, based on the number of PEG-Asp doses administrated pre-SCT. The high-dose group showed superior survival compared to the other two groups in both the entire cohort and in subgroup analysis. Our findings indicate that high-dose PEG-Asp is associated with improved outcome in adult T-ALL undergoing SCT. Keywords T-cell acute lymphoblastic leukemia · Allogeneic hematopoietic stem cell transplantation · Asparaginase · Minimal residual disease Introduction T cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 20–25% of adult ALL cases [1] . Allogeneichematopoietic stem cell transplantation (SCT) has long 􀀍 Hongsheng Zhou [hanson_tcm@126.com](hanson_tcm@126.com) 1 Department of Hematology, Nanfang Hospital, Southern Medical University, Rd 1838 Guangzhou Avenue, Guangzhou 510515, China 2 Guangdong Provincial Clinical Research Center for Hematologic Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China 3 Department of Hematology, Ganzhou People’s Hospital (Nanfang Hospital Ganzhou Hospital), Ganzhou, China been considered the cornerstone of treatment for adult ALL when treated with standard adult protocols [1, 2] . However, the introduction of pediatric-inspired regimens has significantly improved survival rates for adult T-ALL [3–7] . Both allogeneic hematopoietic stem cell transplantation and pediatric-inspired chemotherapy regimens can reduce therelapse rate of adult ALL to approximately 40% . Nevertheless, the optimal integration of SCT with pediatric-inspired chemotherapy in T-ALL to further improve survival remains underexplored. Depletion of asparagine by administration of the asparaginase (Asp) has been a critical component of the pediatricinspired regimen [8–10] . We retrospectively observed that post-SCT survival in adult ALL was associated with the cumulative dose of pegylated-asparaginase (PEG-Asp), with 4 doses demonstrating the best survival. Based on this findings, we designed PDT-ALL-2016 pediatric-inspired protocol (NCT03564704), in which SCT is performed after patients receive four or five doses of PEG-Asp during c

FAQs

What consolidation strategy was tested for adult T-cell acute lymphoblastic leukemia?

The study tested a PEG-Asp-intensified pediatric-inspired consolidation approach (PDT-ALL-2016), where SCT is administered after 4 or 5 doses of pegylated-asparaginase prior to transplantation.

How did the prospective PDT-ALL-2016 cohort compare with the retrospective adult regimen cohort?

The prospective cohort demonstrated superior survival compared with the retrospective adult regimen cohort after PEG-Asp intensification.

What PEG-Asp dosing level before SCT was associated with improved outcomes?

High-dose PEG-Asp (4–5 doses) prior to SCT was associated with better survival versus medium (2–3) and low (0–1) dose groups, including subgroup analyses.

Sep 29, 2026

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