Originally published as JCO Early Release 10.1200/JCO.2003.07.160 on March 7 2003

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Secondary Myeloid Leukemia and Myelodysplastic Syndromes in Patients Treated for Hodgkin’s Disease: A Report From the German Hodgkin’s Lymphoma Study Group

Andreas Josting, Sabine Wiedenmann, Jeremy Franklin, Michael May, Markus Sieber, Juergen Wolf, Andreas Engert, Volker Diehl

From the First Department of Internal Medicine, University Hospital, Cologne, Germany; and the German Hodgkin’s Lymphoma Study Group (GHSG).

Address reprint requests to Andreas Josting, MD, First Department of Internal Medicine, University Hospital Cologne, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany; email: andreas.josting{at}uni-koeln.de.

Purpose: To assess the incidence and outcome of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in patients with Hodgkin’s disease (HD).

Patients and Methods: Between 1981 and 1998, the GHSG conducted three trial generations for early, intermediate, and advanced HD involving a total of 5,411 patients (called HD1 through HD9).

Results: A total of 46 patients with secondary AML/MDS were identified. The median age at diagnosis of leukemia was 47 years (range, 22 to 79 years). Primary therapy was as follows: radiotherapy alone (n = 4); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; n = 1); cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)/ABVD or similar (n = 30); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) baseline (n = 2); and BEACOPP escalated (n = 9). Twelve patients developed AML/MDS after salvage therapy, including four patients who developed AML/MDS after high-dose chemotherapy with autologous stem-cell transplantation. Thirty-six of the secondary malignancies were AML, and 10 malignancies were MDS. After a median observation time of 55 months, incidence of secondary AML/MDS was 1%. Treatment for secondary AML/MDS was as follows: cytarabine (Ara-C)–containing regimens (6-thioguanin, cytarabine, daunorubicin [TAD]/high-dose cytarabine, mitoxantrone [HAM], HAM, Ida-Ara-C (idarubicin + Ara-C), Ida-Flag (idarubicin, fludarabin, Ara-C, G-CSF), and idarubicin, cytarabine, etoposide [ICE]+HAM; n = 11), TAD-chemotherapy (n = 5), other regimens (n = 3), no treatment or supportive care (n = 24), palliative oral chemotherapy (n = 3), and allogeneic stem cell transplantation (n = 9). After 24 months of observation, no difference in freedom from treatment failure and overall survival (2% and 8%, respectively) was observed in patients who developed AML or MDS.

Conclusion: The prognosis of patients with secondary AML/MDS after primary HD is poor. Thus, emphasis should be made to improve initial treatment in an attempt to prevent this complication.

This article was published ahead of print at www.jco.org.

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