Introduction

Pediatric inspired chemotherapy has been successfully applied in adult acute lymphoblastic leukemia (ALL). Short-term efficacy has been repeatedly validated, but few report for long-term outcomes under such treatment modality was published to date. Here we report the outcome of RJ-ALL 2014 protocol for BCR::ABL1 negative B-ALL with the longest follow-up time in Asia.

Methods In this prospective long-term follow-up study of the RJ-ALL 2014 protocol, 153 newly diagnosed patients (pts) with BCR::ABL1-negative B-ALL received intensive treatment with 14 injections of pegaspargase (p-asa) throughout the entire course (2 for induction, 4 for consolidation, 8 for maintenance) : the induction with VIPCP regimen (vincristine, idarubicin, p-asa, cyclophosphamide, methylprednisolone), the consolidation with hyper-CVAD (from MD. Anderson) plus p-asa alternating with high dose methotrexate and cytarabine, and the maintenance with POMP (from BFM protocol) plus p-asa. Central nervous system prophylaxis (16 intrathecal injections for high-risk and 12 for low-risk pts) was integrated. Allogeneic transplantation (HSCT) was applied for eligible pts. Minimal residual disease (MRD) negativity was defined as the absence of leukemia cell at a sensibility of 10-4 by 8-color flow cytometry. Event free survival (EFS) and overall survival (OS) was documented. This study is registered in Chinese Clinical Trial Registry (ChiCTR-ONRC-14004968).

Results From May 2014 to June 2020, 271 pts with ALL were treated at our center. Among them, 153 (56%) pts were BCR::ABL1-negative B-ALL, the median age was 35 (range 14-63), 95 (62.1%) pts were adolescents and young adults (AYA, 14-39 years). At diagnosis, 50 pts (32.9%) had a WBC count ≥30×10⁹/L, 37 pts were identified as molecular or cytogenetic high-risk group (according to the NCCN 2014 guidelines). After induction, the complete remission (CR) rate was 90.83%, while MRD negativity rate was 51.1% (71 pts).

As of July 2025, the median follow-up time was 96 months. The median OS and EFS for all pts were both not reached, and the estimated 10-year OS and EFS were 57.2% and 50.1%, respectively.

AYA pts had better survival than adult pts with 10-year OS of 64% and 46.2%, respectively (p=0.02), and the 10-year EFS were 57% and 39.4%, respectively (p=0.013).

Survival of pts who achieved MRD negativity at the end of induction hardly differ from those who remained MRD positive. The 10-year OS were 57.4% and 56.7%, respectively (p=0.542) and 10-year EFS were 52.5% and 47.6%, respectively (p=0.262). Notably, among 136 pts with MRD data available at 3 months post-induction, 94 (69.1%) achieved MRD negativity. Outcome of MRD negative pts was significantly better than 42 MRD positive pts, with 10-year OS of 68.9% and 43.9%, respectively (p<0.01), and the 10-year EFS were 63.3% and 30.7%, respectively (p<0.01).

In 101 pts without HSCT in CR1, 37 pts accomplished the full 3-year therapy. Their 10-year OS and EFS were both 91.4%. Among them 34 pts are alive with sustained remission. Three of the above 37 patients experienced special events, which we will describe in detail here. Only 2 pts relapsed afterwards: one pt with an E2A::PBX fusion at diagnosis relapsed 6 months after completing treatment and developed PAX5 and c-KIT mutations at relapse, she underwent HSCT at CR2 but still died of leukemia progression; the other pt had rising MRD at the end of 3-year chemotherapy and relapsed 3 months later then died due to disease progression. Besides, 1 female pt developed AML with KMT2A-PTD, DNMT3A and EZH2 mutations 18 months after treatment completion and ultimately died of AML.

In 53 pts (35.6%) underwent HSCT, all except 1 pt were in CR prior to HSCT. Pts who underwent HSCT had better outcomes than other pts. The 10-year OS was 72% and 51.3% respectively (p<0.01), and 10-year EFS were 69% and 42.4% respectively (p<0.01). In multivariate analysis, HSCT was the only independent protective factor for OS and EFS.

Conclusion

Here we report the longest follow-up data for ALL cohort from China. RJ-ALL 2014 protocol including pegaspargase throughout all stages is effective for adult BCR::ABL1 negative B-ALL, especially for pts who accomplished 3-year treatment. HSCT is a protective factor for the prognosis in multiple multivariate analysis. Our data suggest that 3-month MRD statutes is important in predicting 10-year survival outcome.

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2025
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