Chimeric Antigens Receptor T Cell Therapy Improve the Prognosis of Pediatric Acute Lymphoblastic Leukemia With Persistent/Recurrent Minimal Residual Disease in First Complete Remission

Front Immunol. 2022 Jan 7:12:731435. doi: 10.3389/fimmu.2021.731435. eCollection 2021.

Abstract

Background: The presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear.

Methods: We conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission.

Results: A total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8% vs. 51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group [77.8% (95% CI, 64.8-90.7%) vs. 68.7% (95% CI, 47.7-89.6%), P = 0.575] and had a significantly higher 3-year LFS than those in the intensified chemotherapy group [77.8% (95% CI, 64.8-90.7%) vs. 28.6% (95% CI, 4.9-52.3%), P = 0.001]. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion.

Conclusions: Our findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.

Keywords: acute lymphocyte leukemia; chimeric antigen receptor T-cell; measurable residual disease; pediatrics; pre-empty therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adoptive Transfer*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Male
  • Neoplasm, Residual
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Prospective Studies
  • Remission Induction
  • Survival Rate