Managing high-risk CLL during transition to a new treatment era: stem cell transplantation or novel agents?

Blood. 2014 Dec 18;124(26):3841-9. doi: 10.1182/blood-2014-07-586826. Epub 2014 Oct 9.

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) has been considered as the treatment of choice for patients with high-risk chronic lymphocytic leukemia (HR-CLL; ie, refractory to purine analogs, short response [<24 months] to chemoimmunotherapy, and/or presence of del[17p]/TP53 mutations). Currently, treatment algorithms for HR-CLL are being challenged by the introduction of novel classes of drugs. Among them, BCR signal inhibitors (BCRi) and B-cell lymphoma 2 antagonists (BCL2a) appear particularly promising. As a result of the growing body of favorable outcome data reported for BCRi/BCL2a, uncertainty is emerging on how to advise patients with HR-CLL about indication for and timing of HSCT. This article provides an overview of currently available evidence and theoretical considerations to guide this difficult decision process. Until the risks and benefits of different treatment strategies are settled, all patients with HR-CLL should be considered for treatment with BCRi/BCL2a. For patients who respond to these agents, there are 2 treatment possibilities: (1) performing an HSCT or (2) continuing treatment with the novel drug. Individual disease-specific and transplant-related risk factors, along with patient's preferences, should be taken into account when recommending one of these treatments over the other.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Cell Transformation, Neoplastic
  • Clinical Trials as Topic
  • Decision Making
  • Drug Therapy / methods
  • Genes, p53
  • Graft vs Leukemia Effect
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunotherapy / methods
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcr / antagonists & inhibitors
  • Quality of Life
  • Recurrence
  • Remission Induction
  • Risk Factors
  • Stem Cell Transplantation*
  • Treatment Outcome

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • BCR protein, human
  • Proto-Oncogene Proteins c-bcr