Hodgkin Lymphoma Progression Research Articles

Tailored Therapy in Hodgkin Lymphoma, Based on Predefined Risk Factors and Early Interim PET/CT: Israeli H2 Study

Introduction: The aim of therapy in Hodgkin lymphoma (HL) is to maximize response and minimize long-term toxicity.Methods: This multicenter study prospectively evaluated outcomes of HL patients (pts) recruited between 9/2006-8/2013, whose therapy was chosen according to baseline prognostic factors and tailored based on PET/CT results performed after 2 cycles of chemotherapy (PET-2). Pts with classic HL aged 18-60 years, stages I-IV were eligible. Those with early HL were categorized into early favorable (EFD) and unfavorable (EUD) disease groups. After 2 ABVD cycles, EFD pts with negative PET-2 underwent involved nodal radiation therapy (INRT) and EUD pts received 2 more ABVD cycles (total 4) followed by INRT. At physician’s discretion, young pts requiring large-field irradiation could be given a total of 6 ABVD cycles with no RT. Pts with positive PET-2 received 2 additional ABVD cycles (total 4) in EFD and 4 additional cycles (total 6) in EUD followed by RT in both groups. Thus, differences in treatment modality between early disease pts with positive and negative PET-2 included addition of 2 ABVD cycles and mandatory RT for pts with positive PET-2.Pts with advanced HL (B symptoms or stages III/IV) were assigned to therapy based on the International Prognostic Score (IPS). Standard-risk pts (IPS 0-2) initially received 2 ABVD cycles and those with IPS of ≥ 3 received 2 cycles of escalated BEACOPP (EB). If PET-2 was negative or showed minimal residual uptake in a single site, further therapy with 4 ABVD cycles was given and RT to bulky mediastinal masses was omitted. If PET-2 was positive with no evidence of HL progression, therapy was escalated to EB with RT given to bulky mediastinal masses.Results: Data on 356 pts are presented in Table 1. At a median follow-up of 36 months (4-92), 3-y PFS for pts with early disease, overall, and for those with negative and positive PET-2, was 89, 91 and 74%, respectively (p=0.004). For pts with advanced HL, 3-y PFS overall and among those with negative and positive PET-2 was 85, 86 and 75%, respectively (p=0.012). No difference in PFS was observed according to IPS score. RT was given to 45% of pts with early and 12.5% of pts with advanced disease. Three pts died: one during autologous stem cell transplant (SCT), one after allogeneic SCT and one from acute myocardial ischemia.Conclusions: Tailored therapy based on PET-2 is feasible both in early and advanced HL. A positive PET-2 is a marker of inferior prognosis both in early and advanced disease, even when therapy is escalated. For pts with advanced disease and high IPS, initiation of therapy with EB provides a higher rate of negative PET-2 than reported with ABVD. De-escalation of therapy is safe in advanced HL pts with negative PET-2 and does not affect the outcome. RT could be omitted in half of pts with early disease with no difference in PFS. Further follow-up is needed to draw conclusions regarding the long-term efficacy and safety of this personalized approach. Abstract 4409. TableNPts with negative PET-2 N (%)Predictive value of PET-2Treatment adapted based on PET-2Pts experiencing disease progression/relapseNPVPPVEscalation/ reductionN (%)Pos/NegPET-2Total356305(86)91%21%20/6146 (13)12/34Early disease173148 (85)92%32%10/018 (10)7/11Favorable2518 (75)94%16%6/02 (8)1/ 1Unfavorable148130 (88)92%37%4/016 (10)6/10Advanced183157 (86)85%22%10/6128 (15)5/23IPS 0-210694 (90)86%33%10/016 (15)3/13IPS ≥37763(81)84%14%0/6112 (15)2/10PPV = Predictive value of positive PET-2 for relapse/progression DisclosuresNo relevant conflicts of interest to declare.

Outcome and Risk Factors of Hodgkin Lymphoma Patients with Relapse or Progression After Autologous Stem Cell Transplant: A Report From the German Hodgkin Study Group (GHSG).

AbstractAbstract 2633 Background:Today, most patients with Hodgkin Lymphoma (HL) can be cured at first diagnosis. For HL patients suffering from relapse or progression after first line therapy, high dose chemotherapy followed by autologous stem cell transplant (ASCT) is the treatment of choice and cures about 50% of these patients. Those who relapse or progress after ASCT have a very poor prognosis and clearly represent an area of unmet medical need. However, data on this small group of patients is rather limited and no established risk factors are available. Here, we present a recent retrospective analysis from the GHSG database to better characterize HL patients with relapse or progression after ASCT in order to define possible risk factors for the prediction of overall survival. Methods:All trials in the GHSG database were searched for HL patients who relapsed or progressed after ASCT. The information for this retrospective analysis was updated in May 2012. Overall survival after progression of HL following ASCT (OSrr) was the end point of this study. Descriptive statistics and Kaplan Meier estimates of OSrr were used and risk factors for OSrr analyzed. The significance level was set to 0.05. Results:152 patients who relapsed or progressed with HL after ASCT were identified. 149 patients fulfilled the predefined inclusion criteria. With a median observation time of 65 months after progression, 112 patients (75%) had died. OSrr was 63% (95% confidence interval [CI]; 54% to 70%), 51% (95% CI 42% to 58%), and 20% (95% CI 13% to 28%) at 1, 2 and 5 years, respectively. From several risk factors tested, stage (p=0.044) and presence of B-symptoms (p=0.005), both at relapse before ASCT, significantly predicted OSrr. Combination of these two risk factors allowed the identification of three distinct risk categories for the 4 significantly different groups (p=0.013; Figure 1). Accordingly, patients in clinical stage I or II without B-symptoms had a somewhat better prognosis (OSrr 84% [95% CI 67% to 92%], 72% [95% CI 54% to 84%] and 33% [95% CI 18% to 49%] at 1, 2 and 5 years, respectively). Other potential risk factors such as stage at first diagnosis (p=0.80), early, late or multiple relapses before ASCT (p=0.95), and time from ASCT to further progression of HL (p=0.81) were not significant. Conclusions:Current treatment approaches for patients with relapsed or progressive HL after ASCT show disappointing results with 80% of this very high-risk group dying within 5 years. Emerging new drugs such as brentuximab vedotin might improve the outcome of these patients in the future. [Display omitted] Disclosures:von Tresckow:Takeda Pharma GmbH: Honoraria, Travel Grants Other. Borchmann:Millenium The Takeda Oncology Company: Research Funding; Takeda Pharma GmbH: Travel Grants, Travel Grants Other. Engert:Millenium The Takeda Oncology Company: Honoraria.

MTOR as a Target of Everolimus in Refractory/Relapsed Hodgkin Lymphoma

Despite impressive treatment advances, few options for refractory or relapsed Hodgkin Lymphoma (HL) are available and there is a need for new compounds development. A number of promising agents with multiple mechanisms of action are under investigation. Microenvironment and neoangiogenesis are acquiring a rising relevance in the pathophysiology and progression of HL. Everolimus (RAD001) is an oral antineoplastic agent derived from rapamycin, a macrocyclic lactone antibiotic, targeting the mammalian target of rapamycin (mTOR). Although the importance of mTOR signaling in the deregulated cell growth of human neoplastic cells has been recognized, this pathway is also emerging as a key regulator of the tumor response to hypoxia, as well as endothelial and stromal cells function, thereby regulating neoangiogenesis. Furthermore, mTOR plays an important role in anticancer drug resistance. The actions of everolimus within the mTOR pathway in HL result in decreased protein synthesis and cell cycle arrest, as well as in decreased angiogenesis. Everolimus has shown preliminary evidence of efficacy as a single-agent in heavily pretreated relapsed/refractory HL, with an overall fair safety profile. The purpose of this review is to discuss the employment of everolimus as an antiproliferative and antiangiogenic agent in HL and to report the critical role of the mTOR pathway and angiogenesis in this malignancy.

Successful administration of rituximab–bendamustine regimen in the relapse of Hodgkin lymphoma after autologous hemopoietic stem cell transplantation

Treatment options for relapsing Hodgkin lymphoma (HL) are controversial after autologous hemopoietic stem cell transplantation (HSCT). Nevertheless, allogeneic HSCT may be curative if it is performed in complete remission. In 2007, a 22-year-old female patient was diagnosed with nodular sclerosis subtype of classical HL. Her clinical stage was IIAX with unfavorable prognosis. Eight courses of doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy and involved field irradiation were applied, but after 3 months of complete remission, disseminated relapse was recognised by (18)FDG-PET/CT. After two cycles of salvage dexamethasone, cisplatinum, and cytosine arabinoside therapy, further progression was noticed, so the treatment was modified to ifosfamide, gemcitabine, vinorelbine, and prednisone (IGEV) regimen. After two cycles of IGEV regimen, she achieved a complete metabolic remission, which was confirmed by a (18)FDG-PET/CT scan again. She was referred for autologous-HSCT, and a successful stem cell collection was performed in August 2008. However, a rapid progression was detected again, so total body irradiation was applied before the conditioning therapy with R-mini-BEAM regimen. The (18)FDG-PET/CT scan performed 100 days after the autologous-HSCT was still positive. In December 2009, multiple nodal and extranodal progression was detected, so ifosfamide, carboplatine, etoposide, mesna protection rescue treatment was started, but it was ineffective. Based on sporadic data of the literature, rituximab-bendamustine therapy was started in March 2010. After four cycles, she achieved complete metabolic remission, which was verified by (18)FDG-PET/CT. The patient has been referred for an allogeneic HSCT with reduced intensity conditioning. Based on our experience, bendamustine-rituximab salvage therapy can be a suitable option for the treatment of post-transplant progression or relapse of HL.

Intracerebral Progression of Hodgkin Lymphoma in a Man with HIV

Intracerebral relapse of Hodgkin lymphoma is a rare occurrence, with a reported incidence of < 0.5%. To the best of our knowledge, only 4 cases have been reported in the literature. We report the case of a human immunodeficiency virus (HIV)-seropositive man with disseminated Hodgkin lymphoma who presented with left facial weakness and sensory abnormalities as the only symptoms of disease progression 3 months after chemotherapy-induced disease remission. Because of the relative rarity of the condition, there are no randomized controlled trials or evidence-based strategies for managing patients with HIV and intracerebral Hodgkin lymphoma. The diagnostic difficulty of this case emphasizes the necessity for a high index of suspicion for the diagnosis of HIV-associated intracerebral lymphoma in the appropriate clinical setting. In the post-genomic era, the development of sophisticated clinical and/or molecular biomarkers could contribute to earlier diagnosis and potentially improve disease prognosis.

Analysis of Long-Term Outcome and the Risk of Second Malignancies in Hodgkin Lymphoma Survivors

Background: Therapy of Hodgkin lymphoma (HL) can contribute to delayed impairments of health, which some of them (e.g. secondary cancer) can be fatal.Aim: The purpose of this retrospective study was to evaluate long-term outcome of HL survivors and the risk of second malignancies.Methods: The medical report data analysis of 170 patients (pts) with HL treated in one oncological center in Poland between 1979–2005 has been performed. There were 88 females and 82 males, median age 30.5 years (range 16–72). Among the patients there were 22 pts (12.5%) in CSI, 95 pts (55.8%) in CSII, 26 pts (15.4%) in CSIII and 27 pts (15.8%) in CSIV. Half of the 170 pts presented B-symptoms. Chemotherapy (ABVD, MOPP/ABV or MOPP regimen) was given to 155 (93.5%) pts, and radiotherapy alone (mantle-field or involved-field) was given to 11 pts (6.5%). Chemoradiotherapy received 105 pts (61.8%).Results: CR achieved 136 pts (80%), PR 11 pts (6.4%), and progression of HL was observed in 23 pts (13.5%). With a median follow-up of 242 months (range 0–439), there were 37 relapses (21.7%), and 25 deaths (14.7%), usually due to HL progression (20 pts), and also because of secondary cancer (4 pts = 2.4%) and coronary heart disease (1 patient). Five year DFS and OS were 80% and 90% respectively. There was no statistical difference between ABVD and MOPP/ABV regimen efficacy (p=0.94). Late impairments of health were revealed in 78 pts (45.9%), and there were: secondary malignancies, amenorrhea/infertility, skeletal lesions, depressive syndromes, pulmonary fibrosis, polyneuropathy, hypothyroidism, cardiovascular disease, and gastro-duodenal peptic ulcer. Nine pts (5,3%) developed secondary malignancies, i.e.: 2 melanomas, 2 skin basal-cell carcinomas, 1 osteosarcoma, 1 thyroid carcinoma, 1 non-small cell lung cancer, 1 colon carcinoma, 1 cervical carcinoma, and 1 prostate carcinoma. A median time from the end of the treatment to the development of secondary cancer was 114 months (range 28–434). The risk of secondary malignancies development among pts treated with either initial chemotherapy alone or combined modality therapy was similar, and did not reach statistical significance (p=0.20).Conclusions: Chemotherapy or chemoradiotherapy of HL provides freedom from the disease in more than 3/4 of our patients. In the group of fairly young patients such treatment caused a substantial amount of variety of health impairments including secondary malignancies. Despite the high rate of HL curability our study indicates the need of a careful, long term medical surveillance of HL survivors.

Incidence, Predictors, and Significance of Severe Toxicity in Patients with HIV-Associated Hodgkin Lymphoma

Hodgkin lymphoma (HL) occurs in HIV-infected individuals more frequently than in the HIV-negative population and the incidence is rising. Patients (pts) with non-Hodgkin's lymphoma in HIV appear to have improved outcomes if they receive HAART with chemotherapy (CT). ABVD is standard CT for HL and is frequently administered with HAART in pts with HIV-HL. However, some components of the ABVD regimen may interact with antiretroviral (ARV) medications to alter metabolism and increase toxicity. In particular, vinblastine (VBL) is metabolized by CYP3A4 and protease inhibitors, particularly ritonavir (RTV), appear to inhibit this cytochrome potentially leading to higher VBL exposure. Little definitive information is available regarding how interactions might affect clinical outcome. We conducted a retrospective review of 36 pts with HIV-related HL to identify the frequency of neurotoxicity (NT), hematologic toxicity (HT), and lung toxicity (LT), to identify risk factors for severe (grade III–IV) toxicity, and to determine its clinical significance. Clinical data were collected from the CFE database and by chart review from 3 centers. The median age at HL diagnosis (dx) was 41 (range 29–66) years and 34 (94%) were male. HL was advanced stage in 28 (78%). Hasenclever score could be calculated in 23 pts and was 0–4 and ≥5 in 15 and 8 pts respectively. ECOG PS was 0–1 in 13 and ≥2 in 8 (n=21). HIV risk factor was: sexual, n=21 and other, n=5 (n=26). Median CD4 count at HL dx was 210 (2–660) cells/ul (n=31). Median HIV viral load (VL) was undetectable (<50; range <50->500,000) copies/ml (n=25). Hepatitis B and C coinfection was present in 8 and 7 pts respectively (n=29). Prior AIDS was present in 23, all opportunistic infections. Twenty-four pts received HAART with CT. Primary HL CT was: ABVD, n=29 (81%); MOPP/ABV, n=4 (11%); palliative, n=3 (8%). G-CSF was used in 22 pts. All pts received prophylaxis for PCP and 3 for HSV/VZV. HAART included 17 Arts in numerous combinations. Infectious complications were: bacterial infection, n=6; febrile neutropenia, n=4; HSV, n=3; PCP, n=1. HT occurred in 21 (75%) of 28 assessable pts and was grade 3–4 in 18 (64%; 18 and 15 were on HAART, respectively). NT occurred in 14 (50%) pts and was grade 3–4 in 6 (21%; 13 and 5 on HAART respectively, n=28). Of 6 cases of severe NT, 3 were autonomic neuropathy with pseudobowel obstruction that in 1 pt resulted in perforation. Bleomycin LT occurred in 3 pts (n=26). CT dose reduction (DR) of ≥25% in ≥1 agent was required in 9 pts (n=26). Factors associated with grade 3–4 HT were: receiving RTV, p=0.04, HR 2.9 (95% CI 1.1–7.4); and receiving lopinovir (LPV), p=0.02, HR 7.0 (2.3–21.3) and for any HT were: RTV, p=0.004, HR 3.1 (1.3–7.3); emtricitabine, p=0.01, HR 4.8 (1.4–11.6); and LPV, p=0.04, HR 4.4 (1.6–12.1). Factors for grade 3–4 NT were: LPV, p=0.05, HR 10.8 (2.0–59.5) and for any NT was: RTV, p=0.01, HR 4.0 (1.3–12.1). Fourteen pts received RTV and of 8 receiving LPV, 7 received LPV with RTV (p=0.007). At a median follow-up of 15.3 (0.1–154.8) months (mo) 25 pts (69%) are alive. The median overall survival (OS) for all pts was 44.5 (2–154.8) mo and there was no difference in OS by baseline features or the occurrence of HT or NT. However, CT dose reduction was associated with inferior OS (p=0.04, HR 3.9 [1.0–15.7]); although only 1 of 9 deaths was from HL progression; others were: infectious, n=6; and unrelated, n=2. In conclusion, pts with HIV-HL appear to experience a significantly increased incidence of NT compared to rates reported in non-HIV HL pts. In contrast, rates of HT and LT appear to be similar to those in non-HIV HL. The use of RTV or LPV during CT appeared to be associated with an increased risk of NT, suggesting a clinically significant interaction between these ARV agents and CT, particularly VBL. Prospective studies to devise a rational dosing strategy using measurements of ARV and/or CT levels are warranted.

Outcomes for Patients Who Fail High Dose Chemoradiotherapy and Autologous Stem Cell Rescue for Relapsed and Primary Refractory Hodgkin Lymphoma.

Background: Limited data exists regarding the outcome for patients (pts) with relapsed and primary refractory Hodgkin Lymphoma (HL) who fail high dose chemoradiotherapy (HDT) and autologous stem cell rescue (ASCR). The aim of this study is to determine survival time and evaluate the role of second transplantation in pts who have HL-related ASCR failure.Results: At Memorial Sloan Kettering Cancer Center, from 1995–2005, two hundred and twelve pts with relapsed or primary refractory HL underwent HDT/ASCR after responding to ICE-based salvage chemotherapy on one of four consecutive clinical trials. Eighty-one patients failed HDT, including 10 treatment related mortality (4 deaths within 100 days from ASCR, 5 deaths due to secondary malignancies, and 1 death, 10 years after ASCR due to cardiomyopathy); leaving 71 (33%) pts with biopsy-confirmed progression; median time to progression was 5.7 months. There was 43 males (60%), median age at the time of ASCR was 29 (range 17–65). At a median follow-up of 2 years for surviving patients, the median overall survival from ASCR failure was 25 months. Only seventeen of the 71 pts are currently alive (24%), nine (12.6%) of whom are in remission. Remission duration from ASCR of < 3 months predicted for OS; 1 of 17 pts who relapsed within 3 months are currently alive vs 16 of 54 pts with remission duration of > 3 months; median OS are 13.5 and 27.3 months respectively (p=0.02). Treatment regimens following ASCR failure varied and included gemcitabine-based chemotherapy, MOPP, investigational therapies, radiotherapy and second transplantation. The impact of the various treatment regimens on OS following HL-related ASCR failure was difficult to assess due to the heterogeneity of regimens administered. Treatment with a second transplant had a favorable impact on OS, however only two of 17 pts with remission duration < 3 months were able to receive a second transplant because of rapid disease progression. Twenty-three patients underwent a second transplant of which seven are failure free (1/4 autologous, 6/19 allogeneic). The median OS was 40 months for patients transplanted vs. 19.3 months (p=0.05) for patients ineligible for a second transplant.Conclusion: Patients who fail HDT/ASCR due to HL progression have a median OS of two years. Relapse within 3 months of ASCR is associated with a poor OS and investigational or novel therapy should be explored in this cohort of pts. An allogeneic transplant following HL-related ASCR failure is associated with a 30% chance of long term survival and should be strongly considered in pts whose remission duration from their initial ASCR is >3 months.

Elevated Vascular Endothelial Growth Factor Pretreatment Levels Are Correlated with the Tumor Burden in Hodgkin Lymphoma and Continue to Be Elevated in Prolonged Complete Remission

BackgroundVascular endothelial growth factor (VEGF) has been described as an essential cytokine in the regulation of angiogenesis. Its elevation in peripheral blood or bone marrow has been associated with an unfavorable outcome in different hematologic neoplasms. Hodgkin lymphoma represents approximately one fifth of all lymphomas, and the roles of angiogenesis and VEGF in Hodgkin lymphoma have not been well defined at present. Patients and MethodsVascular endothelial growth factor serum levels were determined by enzyme-linked immunosorbent assay in 54 newly diagnosed patients, 26 patients in prolonged complete remission (CR), and 54 healthy controls. Vascular endothelial growth factor levels were compared among the different populations and correlated with prognostic factors and disease evolution. ResultsNewly diagnosed patients showed an increase in VEGF level compared with the CR subgroup (549 pg/mL vs. 327.5 pg/mL; P = 0.023) and with healthy controls (549 pg/mL vs. 140 pg/mL; P < 0.001). Patients in CR also showed an elevated VEGF with respect to healthy controls (327.5 pg/mL vs. 140 pg/mL; P = 0.01). Elevated VEGF was also statistically correlated with newly diagnosed patients with a greater tumor burden (594.5 pg/mL vs. 391 pg/mL; P = 0.009), with ≥ 4 involved areas (608 pg/mL vs. 507 pg/mL; P = 0.036), and with an Eastern Cooperative Oncology Group performance status of ≥ 1 (812 pg/mL vs. 447pg/mL; P = 0.005). Vascular endothelial growth factor was also elevated in advanced-stage disease, in patients with B symptoms, and poorrisk groups, but none of them became statistically significant. ConclusionPathologic angiogenesis is an activated pathway in Hodgkin lymphoma and participates in Hodgkin lymphoma progression. This has been shown by an elevated VEGF level in patients: before first treatment, with greater tumor burden, and with a higher number of involved areas. Furthermore, VEGF continues to be elevated in patients with Hodgkin lymphoma after prolonged CR.

A Case of T/null Anaplastic Large Cell Lymphoma Arising in Lung

Anaplastic large cell lymphoma (ALCL) is a rare non-Hodgkin, T-cell lymphoma, representing only 2-3% of all lymphoid neoplasm's in adults according to World Health Organization (WHO). CD30 antigen-positive, large neoplastic cells characterize ALCL. We present here a 46-year-old male with pulmonary ALCL previously diagnosed with Hodgkin disease. Microscopically, atypical bi-and multinucleated cells with frequent mitoses were present. The neoplastic cells were large and had clear cytoplasm, large vesicular nuclei, and prominent nucleoli. Immunophenotypic analysis revealed LCA, vimentin and CD30 positivity. ALK immunostaining was negative. Immunohistochemical profile was consistent with ALK negative ALCL. The progression of Hodgkin lymphoma to aggressive non-Hodgkin lymphoma (ALCL in this case) is well known entity. After the diagnosis was established, our patient immediately had been referred to the Department of Hematology in order to get appropriate chemotherapy, necessary in such cases.

High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100 patients treated in Vancouver

AbstractBeginning in 1985, patients in British Columbia with Hodgkin lymphoma (HL) that was not controlled by conventional chemotherapy routinely underwent high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT). Long-term complications of HD-ASCT have become apparent as more patients survive without recurrence of HL. Data were obtained retrospectively on the first 100 patients that underwent HD-ASCT for HL in Vancouver, focusing on relapse, treatment-related complications, and the occurrence of late events. Fifty-three patients remain alive (median follow-up, 11.4 years [range, 10.0-17.4 years]) with an overall survival (OAS) of 54% at 15 years. OAS was significantly better in patients in first relapse (67%) than in patients with primary refractory-induction failure (39%) and advanced disease (29%) (P = .002). The major cause of death was progression of HL (32% at 15 years). Treatment-related mortality, including death from second malignancy, was 17% at 15 years. Cumulative risk of a second malignancy was 9% at 15 years. Karnofsky performance status was at least 90% in 47 patients although hypogonadism (20 patients), hypothyroidism (12 patients), unusual infections (10 patients), anxiety or depression (7 patients), and cardiac disease (5 patients) were not uncommon in survivors. HD-ASCT can lead to durable remissions in relapsed or refractory HL with acceptable but definite late toxicity. The occurrence of late events necessitates lifelong medical surveillance. (Blood. 2005;106:1473-1478)

Secondary Malignancies after Autologous Stem Cell Transplantation for Hodgkin's Lymphoma: Incidence and Analysis of Risk Factors.

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.