Genetics and MRD for therapy allocation in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Ribera J.-M.
  • Torrent A.
  • Morgades M.
  • Barrena S.
  • Ribera J.
  • Genescà E.
  • González-Campos J.
  • Martínez-Cibrian N.
  • Hernández-Sánchez A.
  • Barba P.
  • Zapico E.
  • Sánchez R.
  • Novo A.
  • Sitges M.
  • Maluquer C.
  • Such E.
  • Botella C.
  • Queipo de Llano M.-P.
  • Cabrero M.
  • Vicent A.
  • López de Ugarriza P.
  • Tormo M.
  • González-González B.-J.
  • García-Cadenas I.
  • Rodríguez-Medina C.
  • Martínez-Sánchez P.
  • Bermúdez A.
  • Gómez-Centurión I.
  • Herrero M.
  • Ciudad J.
  • Navas-Acosta J.
  • Hermosín L.
  • Serrano J.
  • Raposo J.-Á.
  • Solán L.
  • Roldán-Galiacho V.
  • de Laiglesia A.
  • Gómez-Pérez L.
  • Solé-Rodríguez M.
  • Casado M.-S.
  • Llorente L.
  • Barrios D.
  • Vall-llovera F.
  • Algarra J.-L.
  • Amador M.-L.
  • García-Boyero R.
  • Cladera A.
  • Bergua J.
  • Calasanz M.-J.
  • Granada I.
  • Feliu E.
  • Hernández-Rivas J.-M.
  • Orfao A.

Grupos

Abstract

In adults with Philadelphia chromosome–negative (Ph-) acute lymphoblastic leukemia (ALL) genetic risk is usually combined with measurable residual disease (MRD) assignment to consolidation therapy. However, this combination is not uniform across trials and centralized assessment is not always performed. This study analyzed patient outcomes using centrally assessed MRD and genetics. Patients with high genetic risk (HGR), those who required 2 induction cycles for complete remission (CR), and patients with CR with end-of-induction (EOI) MRD of =0.01% were assigned to allogeneic hematopoietic stem cell transplant (allo-HSCT), whereas the remaining patients were assigned to delayed consolidation and maintenance. HGR for B-cell ALL included KMT2A rearrangements, low hypodiploidy and age of >35 years, homozygous TP53 mutations/deletions, or concomitant IKZF1 and CDKN2A/B deletions. HGR in T-cell ALL (T-ALL) included absence of NOTCH1/FBXW7 mutations and/or K/NRAS or PTEN alterations. Patients with early T-cell precursor (ETP) ALL received a different induction regimen, and all were assigned to allo-HSCT. Median age of 436 patients was 39 years (range, 18-60), 332 with B-lineage ALL and 104 with T-ALL. By intention to treat, 243 patients without ETP ALL (61%) were assigned to allo-HSCT and 157 (39%) to chemotherapy. The 3-year overall survival (OS) probability was 64% (95% confidence interval [CI], 58-69). For patients with CR and EOI MRD of <0.01% without HGR (n = 109), the OS probability was 81% (95% CI, 70-89), compared with 50% (95% CI, 34-63) for MRD-negative patients with HGR (n = 64). In patients with ETP ALL, the probability of 3-year OS was 61% (95% CI, 37-79). The combination of genetics and MRD allows accurate identification of adult patients with Ph- ALL who are candidates for allo-HSCT or chemotherapy. This trial was registered at www.clinicaltrials.gov as NCT04179929. © 2026 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Datos de la publicación

ISSN/ISSNe:
0006-4971, 1528-0020

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Tipo:
Article
Páginas:
-
PubMed:
42081455
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
4,834 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 1

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