title: Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma.
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.
authors.affiliation: Non-Hodgkin Lymphoma-Berlin-Frankfurt-Münster Study Center, Department of Pediatric Hematology and Oncology, Justus-Liebig University, Giessen, Germany;
authors.forename: Christine
authors.initials: C
authors.lastname: Damm-Welk
authors.forename: Lara
authors.initials: L
authors.lastname: Mussolin
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Marta
authors.initials: M
authors.lastname: Pillon
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Ilske
authors.initials: I
authors.lastname: Oschlies
authors.forename: Emanuele S G
authors.initials: ES
authors.lastname: d'Amore
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Woessmann
authors.forename: Angelo
authors.initials: A
authors.lastname: Rosolen
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D006801:Humans; D015994:Incidence; D017728:Lymphoma, Large-Cell, Anaplastic / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D018365:Neoplasm, Residual / Q000175:diagnosis*; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases