Secondary Malignancies after Autologous Stem Cell Transplantation for Hodgkin’s Lymphoma: Incidence and Analysis of Risk Factors.
Authors: Constans Mireia , Sureda Anna , Arranz Reyes , Caballero Maria Dolores , Lahuerta Juan Jose , Hernandez-Boluda Juan Carlos , Vidal Maria Jesus , Garcia-Laraña Jose , Rifon Jose , Ribera Josep Maria , Fernandez-Abellan Pascual , Moraleda Jose Maria , Bernal Maria Teresa , Mateos Maria Victoria , Martin-Mateos Maria , Cordoba Rafael , Garcia-Conde Javier , Sierra Jorge , Conde Eulogio ,   for the Spanish Cooperative Group (GEL/TAMO).
Published: October 2019

Abstract
We have analyzed the incidence and risk factors for developing a secondary malignancy (SM) in patients with Hodgkin’s lymphoma (HL) treated with an autologous stem cell transplantation (ASCT). From 639 patients autografted for HL [383 males and 256 females with a median age of 30 (1–66) years and a median follow-up after ASCT of 53 (3–202) months] reported to the GEL/TAMO Spanish Cooperative Group between January/1984 and January/2003, 37 patients (6% of the series) developed a SM at a median time of 35 months after ASCT [24 patients (65%) a myelodisplastic syndrome (MDS)/acute myelogenous leukemia (AML), 3 patients (8%) a non Hodgkin’s lymphoma (NHL) and 10 patients (29%) a solid tumor (ST)]. There were 24 males and 13 females with a median age of 39 (13–60) years [23 patients (61%), <40 years] at ASCT. Twenty-three patients (62%) presented with advanced disease at diagnosis, 14 patients (38%) had B symptoms, seven (19%) bone marrow (BM) involvement and 13 (35%), bulky mediastinal disease. Eighteen patients (49%) had previously received nitrogen mustard containing therapies, eight patients (22%) had been splenectomized before ASCT and 18 (49%) had received complementary radiotherapy. Twenty patients (70%) had received more than two lines of chemotherapy (CT) before ASCT. Fourteen patients (38%) were in complete remission (CR) at ASCT, 16 patients (43%) were in chemosensitive relapse and seven in resistant relapse. In 25 patients (68%), peripheral blood was used as the source of hematopoietic stem cells and in the remaining 12 patients, BM. Only three patients received total body irradiation as part of the conditioning regimen. Time between diagnosis and ASCT was >24 months in 23 patients (62%). Twenty-three patients (62%) were in CR when they developed the SM and the remaining 14 (38%), had active disease. Median time to develop a myeloid malignancy was of 12 (4 – 34) months, to develop a lymphoid malignancy (T cell NHL, 2 patients; B cell NHL, 1 patient) was of 23 (12 – 31) months and to develop a ST (2 squamous cell carcinomas of the lung, 2 rabdomisarcomas, 2 adenocarcinomas of the rectum, 1 basocelular carcinoma, 2 in situ bladder carcinoma and one oropharyngeal carcinoma) of 60 (34 – 91) months, respectively (p = 0.0001). Twenty eight patients have died: 18 patients (64%) due to the SM and 10 (36%) due to HL progression. Multivariate analysis identified age at ASCT > 40 years and the time between diagnosis and ASCT > 24 months as the only two bad prognostic factors for developing a SM [relative risk (RR) 2.48, 95% confidence interval (CI) (1.20–5.10), p = 0.01 and 2.17, 95%CI (1.06–4.46), p = 0.034], respectively. The risk of developing a SM is a real long time side effect after an autologous procedure in HL patients. Advanced age at ASCT and a long time interval between diagnosis and ASCT, a probable surrogate marker of the amount of CT given to the patient before the ASCT have been, in our experience, the only two risk factors for developing this complication.