Ann Hematol (1997) 74 : 103–110 Q Springer-Verlag 1997 ORIGINAL ARTICLE R. Maurizi Enrici 7 A. P. Anselmo 7 M. F. Osti M. Santoro 7 S. Sbarbati 7 V. Tombolini F. Mandelli 7 E. D’Arcangelo 7 C. Biagini Acute nonlymphocytic leukemia: onset after treatment for Hodgkin’s disease Received: 18 June 1996 / Accepted: 20 November 1996 R. Maurizi Enrici (Y) Chair of Radiation Oncology, Hospital “S. Maria di Collemaggio,” University of L’Aquila, I-67100 L’Aquila, Italy M. F. Osti 7 M. Santoro 7 S. Sbarbati 7 V. Tombolini C. Biagini Department of Radiation Oncology, Institute of Radiology, Policlinico Umberto I, Viale Regina Elena, 432, University of Rome “La Sapienza,” I-00161 Rome, Italy A. P. Anselmo 7 F. Mandelli Department of Human Biopathology, Hematology Section, Via Benevento, 6, University of Rome “La Sapienza,” I-00161 Rome, Italy E. D’Arcangelo Department of Statistics, Probability and Applied Statistics, Piazzale Aldo Moro, 5, University of Rome “La Sapienza”, I-00161 Rome, Italy Abstract This study was undertaken to examine the in- fluence of various factors on the occurrence of acute nonlymphocytic leukemia (ANLL) in a group of long- term survivors of Hodgkin’s disease (HD). From 1972 to 1992, 1045 patients with HD were assessed and treated at the Department of Radiation Oncology, the Institute of Radiology, and the Department of Human Biopathology, Hematology Section, University of Rome “La Sapienza.” The average follow-up was 72 months. For a more accurate calculation of the risk of ANLL occurrence, the patients were first divided into three subgroups according to initial treatment and then according to the total treatment they had received. Moreover, to establish the probable connection be- tween leukemia and splenic treatment the patients were also divided into three subgroups (splenectomy, splenic irradiation, and no splenectomy/no splenic irradiation). Sixteen cases of ANLL were recorded, giving an over- all risk of 0.2% at 5 years and 3.4% at 20 years. In 12 patients overt leukemia was preceded by a myelodys- plastic syndrome. Five cases had evaluable chromo- some analysis. Clonal chromosome abnormalities were demonstrated in two patients, whereas three patients showed an apparently normal karyotype. Bone marrow agar cultures were analyzed in two patients and were abnormal in both cases. In the radiotherapy (RT) group, the cumulative risk was 0.4% at 10 years and 3.2% at 15 and 20 years; in the chemotherapy (CT) group it was 1.2% at 10, 15, and 20 years; in the com- bined group it was 3.7% at 10 years and 4.9% at 15 and 20 years. In the multivariate analysis, MOPP treatment with or without RT is a statistically significant variable for ANLL occurrence (pp0.009). This study demon- strates that splenic treatment does not lead to ANLL. Treatment with MOPP alone and with MOPP plus RT can increase the risk of ANLL. Key words Hodgkin’s disease 7 Acute nonlymphocytic leukemia 7 Risk factors 7 Radiotherapy 7 Chemotherapy Introduction At present, new developments in radiotherapy (RT) and in chemotherapy (CT) are helping to improve the overall survival and cure rates of patients with Hodg- kin’s disease (HD). However, treatment-related com- plications have taken on enormous clinical importance. As reported in most publications, these include injuries of the gastrointestinal tract, pulmonary function im- pairment, cardiac toxicity, hypothyroidism, and second cancers [1, 9, 26, 36, 38, 40, 51, 53]. One serious complication is the occurrence of acute nonlymphocytic leukemia (ANLL). The increase in the risk of ANLL has been associated with host-related fac- tors and with the type of treatment patients have been given [43]. Several authors report that the risk is higher in patients treated with combined RT and CT regimens including mechloretamine and procarbazine [7, 15, 21, 29, 44, 50]. Peak incidence is 4–6 years after treatment with CT [21], while the risk of solid tumors increases over a longer period of time. On the other hand, recent stud- ies [10, 15, 50] do not show an increase in the risk of