Blinatumomab Intensification for MRD-Negative Acute B-Cell Lymphoblastic Leukemia Before Allogeneic Hematopoietic Stem Cell Transplantation

Korábbi kezelés

• Prior exposure to blinatumomab, chimeric antigen receptor (CAR) T-cell therapy, or anti-CD22 immunotoxins.
• Clinically significant cardiovascular disease, including uncontrolled arrhythmia, uncontrolled hypertension, congestive heart failure, NYHA class III or IV heart disease, or myocardial infarction within 3 months prior to screening.

Más betegség

• Other severe comorbidities that may limit participation in the trial (e.g., severe infection, renal failure).
• Known HIV infection or uncontrolled severe viral hepatitis.

Egyéb

• Pregnant or breastfeeding women.

• Diagnosed with B-cell acute lymphoblastic leukemia (B-ALL) according to the 2022 WHO classification.
• Age between 18 and 65 years. 3. Meets the National Comprehensive Cancer Network (NCCN) criteria for high-risk B-ALL, based on clinical or cytogenetic/molecular features:
• Clinical high-risk features (any of the following):
  • Age > 35 years
  • Peripheral WBC count > 30 × 10⁹/L
  • Cytogenetic/molecular high-risk features (any of the following):
• Cytogenetic and molecular high-risk features (at least one of the following):
  • Hypodiploidy (<44 chromosomes)
  • TP53 mutation
  • KMT2A rearrangement
  • MLL rearrangement
  • HLF rearrangement
  • ZNF384 rearrangement
  • MEF2D rearrangement
  • MYC rearrangement
  • BCR-ABL1-like (Ph-like) ALL, including:
  • JAK pathway rearrangements (CRLF2r, EPORr, JAK1/2/3r, TYK2r, SH2B3 mutation, IL7R mutation, JAK1/2/3 mutations)
  • ABL-class rearrangements (ABL1, ABL2, PDGFRA, PDGFRB, FGFR1)
  • Other kinase fusions (e.g., NTRK3r, FLT3r, LYNr, PTK2Br)
  • PAX5alt
  • t(9;22)(q34.1;q11.2); BCR-ABL1 with IKZF1 mutation and/or prior chronic myeloid leukemia (CML)
  • Intrachromosomal amplification of chromosome 21 (iAMP21)
  • IKZF1 alteration
  • Complex karyotype (≥5 chromosomal abnormalities) 4. CD19-positive by immunophenotyping. 5. BCR::ABL1-negative. 6. Achieved complete remission (CR) after induction therapy. 7. Measurable residual disease (MRD)-negative by flow cytometry (FCM). 8. Availability of a matched sibling donor, haploidentical related donor, or matched/unmatched unrelated donor.
  • ECOG performance status score of 0-2. 10. Creatinine clearance ≥ 60 mL/min (by Cockcroft-Gault formula). 11. AST and ALT ≤ 3 × upper limit of normal (ULN); total bilirubin ≤ 2 × ULN. 12. Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiography. 13. Expected survival > 8 weeks. 14. Signed written informed consent, with ability to understand and comply with the study protocol.