Page 165 - 2020_08-Haematologica-web

Non-Hodgkin Lymphoma
Quantification of minimal disseminated disease by quantitative polymerase chain reaction and digital polymerase chain reaction for NPM-ALK as a prognostic factor in children with anaplastic large cell lymphoma
Ferrata Storti Foundation
Haematologica 2020 Volume 105(8):2141-2149
Christine Damm-Welk,1° Nina Kutscher,1 Martin Zimmermann,2 Andishe Attarbaschi,3 Jutta Schieferstein,1 Fabian Knörr,4 Ilske Oschlies,5 Wolfram Klapper5 and Wilhelm Woessmann1,4
1NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, Giessen, Germany; 2Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany; 3Department of Pediatric Hematology and Oncology, St. Anna Children‘s Hospital, Medical University of Vienna, Vienna, Austria; 4Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany and 5Institute of Pathology, Hematopathology Section and Lymph Node Registry, Kiel, Germany.
°Present address: Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
ABSTRACT
Detection of minimal disseminated disease is a validated prognostic factor in ALK-positive anaplastic large cell lymphoma. We previ- ously reported that quantification of minimal disease by quantita- tive real-time polymerase chain reaction (RQ-PCR) in bone marrow applying a cut-off of 10 copies NPM-ALK/104 copies of ABL1 identifies very high-risk patients. In the present study, we aimed to confirm the prognostic value of quantitative minimal disseminated disease evaluation and to validate digital polymerase chain reaction (dPCR) as an alternative method. Among 91 patients whose bone marrow was analyzed by RQ- PCR, more than 10 normalized copy-numbers correlated with stage III/IV disease, mediastinal and visceral organ involvement and low anti-ALK antibody titers. The cumulative incidence of relapses of 18 patients with more than 10 normalized copy-numbers of NPM-ALK was 61±12% com- pared to 21±5% for the remaining 73 patients (P=0.0002). Results in blood correlated with those in bone marrow (r=0.74) in 70 patients for whom both materials could be tested. Transcripts were quantified by RQ-PCR and dPCR in 75 bone marrow and 57 blood samples. Copy number esti- mates using dPCR and RQ-PCR correlated in 132 samples (r=0.85). Applying a cut-off of 30 copies NPM-ALK/104 copies ABL1 for quantifica- tion by dPCR, almost identical groups of patients were separated as those separated by RQ-PCR. In summary, the prognostic impact of quantifica- tion of minimal disseminated disease in bone marrow could be confirmed for patients with anaplastic large cell lymphoma. Blood can substitute for bone marrow. Quantification of minimal disease by dPCR provides a promising tool to facilitate harmonization of minimal disease measure- ment between laboratories and for clinical studies.
Introduction
ALK-positive anaplastic large cell lymphomas (ALCL) in children and adolescents are characterized by translocations involving the ALK gene on chromosome 2p23.1 About 90% of ALK-positive ALCL carry the translocation t(2;5)(p23;q35) resulting in the fusion gene NPM-ALK.2-4 Between 25% and 35% of patients relapse with current treatment protocols.5-9
Correspondence:
CHRISTINE DAMM-WELK
c.damm-welk@uke.de
WILHELM WOESSMANN
w.woessmann@uke.de
Received: July 17, 2019. Accepted: October 24, 2019. Pre-published: October 24, 2019.
doi:10.3324/haematol.2019.232314
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/8/2141
©2020 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2020; 105(8)
2141
ARTICLE