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Lymphoma

Use of minimal disseminated disease and immunity to NPM-ALK antigen to stratify ALK-positive ALCL patients with different prognosis

Leukemia volume 27, pages 416–422 (2013)Cite this article

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Abstract

We studied the prognostic value of minimal disseminated disease (MDD) and anti-ALK immune response in children with NPM-ALK-positive anaplastic-large cell lymphoma (ALCL) and evaluated their potential for risk stratification. NPM-ALK transcripts were analyzed by RT-PCR in bone marrow/peripheral blood of 128 ALCL patients at diagnosis, whereas ALK antibody titers in plasma were assessed using an immunocytochemical approach. MDD was positive in 59% of patients and 96% showed an anti-ALK response. Using MDD and antibody titer results, patients could be divided into three biological risk groups (bRG) with different prognosis: high risk (bHR): MDD-positive and antibody titer ⩽1/750, 26/128 (20%); low risk (bLR): MDD negative and antibody titer >1/750, 40/128 (31%); intermediate risk (bIR): all remaining patients, 62/128 (48%). Progression-free survival was 28% (s.e., 9%), 68% (s.e., 6%) and 93% (s.e., 4%) for bHR, bIR and bLR, respectively (P<0.0001). Survival was 71% (s.e., 9%), 83% (s.e., 5%) and 98% (s.e., 2%) for bHR, bIR and bLR (P=0.02). Only bHR and histology other than common type were predictive of higher risk of failure (hazard ratio 4.9 and 2.7, respectively) in multivariate analysis. Stratification of ALCL patients based on MDD and anti-ALK titer should be considered in future ALCL trials to optimize treatment.

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Acknowledgements

The study was supported by Fondazione Città Della Speranza, Associazione Italiana contro le Leucemie (AIL) and by Camera di Commercio di Venezia. The study was also supported by a grant from the Deutsche Jose Carreras Leukämie-Stiftung (DJCLS08/09) to WW. CDW and WW are additionally supported by the Forschungshilfe peiper. KP was supported by Leukemia and Lymphoma research, the Sam Foye Fund, Julian Starmer-Smith Lymphoma fund and the National Institute for Health Research Biomedical Research Center Program. We are grateful to Dr Elisa Carraro for data management. We thank the Colleagues from various AIEOP and BFM centers for contributing biological samples and patient clinical information.

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Author notes

  1. L Mussolin and C Damm-Welk: These authors contributed equally to this work.

  2. A Rosolen and W Woessmann: Co-senior authors.

Authors and Affiliations

  1. Clinica di Oncoematologia Pediatrica and Fondazione Città della Speranza, Azienda Ospedaliera-Università di Padova, on behalf of the Linfoma non-Hodgkin Working Group AIEOP (Associazione Italiana Emato-Oncologia Pediatrica), Padova, Italy

    L Mussolin, M Pillon, G Franceschetto & A Rosolen

  2. Non-Hodgkin’s Lymphoma-Berlin-Frankfurt-Muenster Study Centre, Justus–Liebig-University, Giessen, Germany

    C Damm-Welk, M Zimmermann, A Reiter & W Woessmann

  3. Nuffeld Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK

    K Pulford

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  1. L Mussolin
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Correspondence to A Rosolen.

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Mussolin, L., Damm-Welk, C., Pillon, M. et al. Use of minimal disseminated disease and immunity to NPM-ALK antigen to stratify ALK-positive ALCL patients with different prognosis. Leukemia 27, 416–422 (2013). https://doi.org/10.1038/leu.2012.205

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