title: Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials.
abstract: Purpose Clinical characteristics, therapeutic approaches, and prognosis of late relapse (LR) in patients with classic Hodgkin lymphoma (cHL) are poorly understood. We performed a comprehensive analysis of LR of Hodgkin lymphoma (LR-HL). Methods To estimate the incidence of LR-HL, we retrospectively analyzed 6,840 patients with cHL included in the German Hodgkin Study Group trials HD7 to HD12. Patients who experienced a relapse > 5 years into remission were compared with patients in continued remission for > 5 years and with those who experienced a relapse ≤ 5 years after first diagnosis. Results With a median observation time of 10.3 years, 141 incidences of LR-HL were observed. Cumulative incidences at 10, 15, and 20 years rose linearly and were 2.5%, 4.3%, and 6.9%, respectively. The standardized incidence ratio for HL with respect to age- and sex-matched German reference data was 84.5 (95% CI, 71.2 to 99.7). LR-HL was more frequently observed in patients with early-stage favorable than unfavorable or advanced stage at first diagnosis (15-year cumulative incidence, 5.3% v 3.9% and 3.9%, respectively; P = .01). Overall survival from first diagnosis was worse after LR compared with nonrelapse survivors (10-year estimate, 95.8% v 86.1%; hazard ratio, 2.5; 95% CI, 1.7 to 3.5; P < .001). In patients with LR-HL, survival was better compared with 466 patients with earlier relapse (hazard ratio, 0.6; 95% CI, 0.4 to 0.9, P = .01). Forty-four percent and 49% of patients with LR-HL and earlier relapse, respectively, received stem cell transplantations. Conclusion Apart from treatment-associated adverse effects, survivors after initially successful therapy for cHL are at an 85-fold risk for recurrence of disease compared with the general German population. After risk-adapted treatment strategies, especially in early-stage favorable HL, regular clinical follow-up is recommended for timely detection of LR-HL. With adequate treatment, prognosis of LR-HL is better compared with early relapses.
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bröckelmann
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Helen
authors.initials: H
authors.lastname: Goergen
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kohnhorst
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Bastian
authors.initials: B
authors.lastname: von Tresckow
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Alden
authors.initials: A
authors.lastname: Moccia
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Markova
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Julia
authors.initials: J
authors.lastname: Meissner
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kerkhoff
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Fuchs
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Borchmann
authors.affiliation: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D005858:Germany / Q000453:epidemiology; D006689:Hodgkin Disease / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult