Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma

Blood. 2014 Jan 16;123(3):334-7. doi: 10.1182/blood-2013-09-526202. Epub 2013 Dec 2.

Abstract

Detection of minimal disseminated disease (MDD) at diagnosis correlates with relapse risk in children with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL). We investigated whether minimal residual disease (MRD) positivity by qualitative reverse-transcriptase polymerase chain reaction (RT-PCR) for Nucleophosmin (NPM)-ALK during treatment identifies patients at the highest relapse risk. Blood and/or bone marrow of 180 patients with NPM-ALK-positive ALCL treated with Berlin-Frankfurt-Münster-type protocols were screened for NPM-ALK transcripts at diagnosis; 103 were found to be MDD-positive. MRD before the second therapy course could be evaluated in 52 MDD-positive patients. MRD positivity correlated with uncommon histology. The cumulative incidence of relapses (CIR) of 26 MDD-positive/MRD-positive patients (81% ± 8%) was significantly higher than the CIR of 26 MDD-positive/MRD-negative (31% ± 9%) and 77 MDD-negative patients (15% ± 5%) (P < .001). Five-year survival of MDD-negative and MDD-positive/MRD-negative patients was 91% ± 3% and 92% ± 5%, respectively, compared with 65% ± 9% of MDD-positive/MRD-positive patients (P < .001). Early evaluation of MRD in NPM-ALK-positive ALCL identifies patients with a very high relapse risk and inferior survival.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Antineoplastic Agents / therapeutic use
  • Bone Marrow / pathology
  • Child
  • Disease-Free Survival
  • Humans
  • Incidence
  • Lymphoma, Large-Cell, Anaplastic / diagnosis*
  • Lymphoma, Large-Cell, Anaplastic / mortality
  • Lymphoma, Large-Cell, Anaplastic / pathology*
  • Neoplasm, Residual / diagnosis*
  • Nuclear Proteins / metabolism*
  • Prognosis
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Nuclear Proteins
  • nucleophosmin
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases