Impact of first- and second-line treatment for Hodgkin's lymphoma on the incidence of AML/MDS and NHL--experience of the German Hodgkin's Lymphoma Study Group analyzed by a parametric model of carcinogenesis.
BACKGROUND
Using a parametric carcinogenesis model, we disentangle the superimposing effects of primary and relapse therapies of Hodgkin's disease on secondary neoplasias.


METHODS
We analyze eight randomized trials of the German Hodgkin's lymphoma study group [5357 individuals, 67 secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and 97 secondary non-Hodgkin's lymphoma (NHL)]. Primary therapies were divided into four groups: radiotherapy alone, moderately dosed COPP/ABVD-like chemotherapies for intermediate and advanced stages and BEACOPP escalated.


RESULTS
For secondary AML/MDS, the hazards after primary therapies are proportional (maximum at 3.4 years), while the hazard after relapse therapy is more peaked (maximum at 1.8 years). Intermediate and advanced stage chemotherapy resulted in a cumulative risk of 1.5%, while the risk after BEACOPP escalated is higher (4.4%, P = 0.004) and comparable with that after relapse therapy (4.5%). For secondary NHL, there are no differences in cumulative risk between the primary therapies (2.9%), while the risk after relapse therapy is increased (6.6%, P = 0.002).


CONCLUSIONS
BEACOPP escalated moderately increases the risk of secondary AML/MDS but not NHL. No differences were found between other chemotherapies of advanced stages and intermediate stages. Secondary AML/MDS occurs faster after relapse treatment than after primary treatment.
Scholz
M
M
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig; LIFE (Leipzig Interdisciplinary Research Cluster of Genetic Factors, Phenotypes and Environment), University of Leipzig, Leipzig. Electronic address: markus.scholz@imise.uni-leipzig.de.
Engert
A
A
Klinik 1 für Innere Medizin, University Hospital of Cologne, German Hodgkin Study Group, Cologne, Germany.
Franklin
J
J
Klinik 1 für Innere Medizin, University Hospital of Cologne, German Hodgkin Study Group, Cologne, Germany.
Josting
A
A
Klinik 1 für Innere Medizin, University Hospital of Cologne, German Hodgkin Study Group, Cologne, Germany.
Diehl
V
V
Klinik 1 für Innere Medizin, University Hospital of Cologne, German Hodgkin Study Group, Cologne, Germany.
Hasenclever
D
D
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig.
Loeffler
M
M
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig.
D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001761:Bleomycin / Q000009:adverse effects; D003520:Cyclophosphamide / Q000009:adverse effects; D003606:Dacarbazine / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects; D005047:Etoposide / Q000009:adverse effects; D006037:Glyoxal / Q000009:adverse effects; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D011238:Prednimustine / Q000009:adverse effects; D011241:Prednisone / Q000009:adverse effects; D011344:Procarbazine / Q000009:adverse effects; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects; D014750:Vincristine / Q000009:adverse effects
D001761:Bleomycin; D011344:Procarbazine; D006037:Glyoxal; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D003606:Dacarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011238:Prednimustine; D007069:Ifosfamide; D011241:Prednisone