Impact of Novel Targeted Therapies and Cytogenetic Risk Groups on Outcome After Allogeneic Transplantation for Adult ALL

Zaid H. Abdel Rahman, Michael G. Heckman, Kevin Miller, Hassan Alkhateeb, Mrinal S. Patnaik, Lisa Z. Sproat, Liuyan Jiang, Vivek Roy, Hemant S. Murthy, Ernesto Ayala, William J. Hogan, Patricia T. Greipp, Mohamed A. Kharfan-Dabaja, Mark R. Litzow, James M. Foran

Research output: Contribution to journalArticlepeer-review

Abstract

Novel high-risk groups have recently been identified in adult acute lymphoblastic leukemia (ALL), including Philadelphia-like, therapy-related, and measurable residual disease after induction therapy. Furthermore, modern targeted therapies have recently been incorporated into ALL management; rituximab for CD20-positive and blinatumomab for measurable residual disease after induction therapy or relapsed or refractory disease. Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended as consolidation therapy for high-risk ALL; however, its relative benefit for these high-risk groups and after novel therapies is unclear. We performed an analysis of posttransplantation outcomes in a cohort of 261 consecutive patients who underwent allo-HCT for ALL at the 3-site Mayo Clinic Cancer Center (January 1, 2008–December 31, 2018). With a median (range) follow-up of 22.4 months (0.5-135.0), the 100-day and 5-year cumulative incidences of nonrelapse mortality rates were 6.5% and 26.7%, respectively. The 5-year cumulative incidences of relapse and death were 22.6% and 46.2%, respectively. The 1-year estimate of the composite endpoint of graft-versus-host disease/relapse-free survival was 39.3%. We observed no associations of novel high-risk groups or modern targeted therapies with overall survival, nonrelapse mortality, or relapse in multivariable analysis. An increased risk of relapse was observed with T-ALL (hazard ratio, 2.16; 95% confidence interval, 1.14-4.09; P = .02) and hypodiploidy/near-triploidy (hazard ratio, 2.84; 95% confidence interval, 1.06-7.62; P = .04). Our analysis suggests that novel high-risk groups derive a similar benefit from allo-HCT as traditional high-risk adult ALL and that novel targeted therapies do not seem to independently predict for posttransplantation outcomes. It also calls for further exploration of maintenance strategies after Allo-HCT to prevent relapse in high-risk subgroups.

Original languageEnglish (US)
Pages (from-to)165.e1-165.e11
JournalTransplantation and Cellular Therapy
Volume27
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • Acute lymphoblastic leukemia
  • Allo-HCT
  • Allogeneic transplantation
  • Blinatumomab
  • Hypodiploidy
  • Ph-like

ASJC Scopus subject areas

  • Hematology
  • Transplantation
  • Immunology and Allergy
  • Cell Biology
  • Molecular Medicine
  • Medicine(all)

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