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Purpose Timing, appropriate amount, and composition of treatment before high-dose therapy and autologous stem-cell transplantation (ASCT) in patients with poor-risk, aggressive non-Hodgkin's lymphoma (NHL) are still unknown. We conducted two consecutive multicenter phase II trials with up-front, high-dose, sequential chemotherapy and ASCT in poor-risk, aggressive NHL. Both trials had identical inclusion criteria and only differed in amount and duration of induction treatment before ASCT. Patients and Methods Between 1994 and 2001, 147 newly diagnosed, poor-risk, aggressive NHL patients, age ≤ 65 years with stage III to IV and lactate dehydrogenase (LDH) more than 1.5× upper limit of normal (ULN), entered the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) -27 and HOVON-40 trials. Treatment in HOVON-27 consisted of two up-front, high-dose induction courses followed by carmustine, etoposide, cytarabine, and melphalan plus ASCT in responding patients. In HOVON-40, the same treatment was preceded by three intensified courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Results Patient characteristics in both trials were comparable: 80% had diffuse large B-cell lymphoma, 77% had stage IV disease, and median LDH levels were 3.1× ULN. Complete remission (CR) in both trials was 45% to 51%. Before ASCT, CR was 14% in HOVON-27 versus 28% in HOVON-40 (P = .03). Treatment failure was similar (27%). Four-year survival estimates in HOVON-27 compared with HOVON-40 were overall survival, 21% v 50% (P = .007); event-free survival, 15% v 49% (P = .0001); and disease-free survival, 34% v 74% (P = .008). This different outcome favoring HOVON-40 remained highly significant when correcting for competing risk factors in multivariate analysis. Conclusion In patients with poor-risk, aggressive NHL, addition of intensified CHOP before up-front, high-dose, sequential therapy and ASCT significantly improved the duration of response and survival.

Purpose: To confirm the feasibility and estimate the efficacy of methotrexate (MTX), teniposide, carmustine, and methylprednisolone (MBVP) chemotherapy combined with radiotherapy (RT) for patients with non–AIDS-related primary CNS lymphoma (PCNSL) treated in a multicenter setting. Patients and Methods: Treatment consisted of two cycles of MBVP (MTX 3 g/m2 days 1 and 15, teniposide 100 mg/m2 days 2 and 3, carmustine 100 mg/m2 day 4, methylprednisolone 60 mg/m2 days 1 to 5, and two intrathecal injections of MTX 15 mg, cytarabine 40 mg, and hydrocortisone 25 mg) followed by 40 Gy of RT. Primary end points were response and safety of this regimen. Results: Twelve centers included 52 patients who were all analyzed on an intent-to-treat basis. Median follow-up of all patients was 27 months. One patient progressed and died before treatment, and five patients died during treatment. Four patients received RT after one cycle of chemotherapy, and 42 patients completed the entire treatment. Hematologic grade 3 and 4 toxicity was seen in 78% of patients for leukocytes and 24% of patients for platelets. The overall response rate of all 52 patients was 81%. Two patients who did not fulfill the criteria of objective response survived more than 1 year; one of them is still alive without disease. Eighteen patients died; 11 deaths were a result of tumor, five were probably treatment-related, one was caused by late leukoencephalopathy, and one was a result of intercurrent disease. Median estimated overall survival was 46 months. Conclusion: MBVP followed by RT for PCNSL has a high response rate. However, the 10% toxic death rate during treatment in a multicenter setting underlines the need for highly specialized care.

40 Background: The risk of developing gastrointestinal (GI) cancer is increased in Hodgkin lymphoma survivors. This study aims to compare overall survival of GI cancer in Hodgkin lymphoma survivors with survival of first primary GI cancer patients. Methods: This cohort study compared overall survival of GI cancer patients in a Hodgkin lymphoma survivor population (HL-GI (n = 92) including esophageal (n = 25), gastric (n = 31), small intestinal (n = 2), colorectal cancer (n = 34)) with survival of a population-based cohort of first primary GI cancer patients (GI-1, n = 911) which was generated by individual matching of the 92 cases, based on tumor location, gender, age and year at diagnosis. Clinical characteristics were compared by Chi square tests. Cox regression was used for multivariable survival analysis (corrected for age, gender, and clinicopathological characteristics related to the GI tumor). Results: When comparing HL-GI and GI-1 patients, no differences in tumor stage, grade of differentiation or frequency of surgery were found. HL-GI patients were less frequently treated for their GI tumor with radiation therapy (7% vs. 24% in GI-1 patients, p < 0.001) or chemotherapy (28% vs. 41%, p = 0.02). Overall 5-year and 20-year survival of HL-GI patients and GI-1 patients was non-significantly lower (28% vs. 38%, p = 0.13 and 19% vs. 29%, p = 0.06, respectively). This result was confirmed multivariably (5-year survival, p = 0.33, 20-year survival, p = 0.14). Also, for esophageal, gastric and colorectal cancer separately, no differences in overall survival were found between HL-GI patients and GI-1 patients. Conclusions: Long-term overall survival of GI cancer patients is similar in Hodgkin lymphoma survivors and first primary GI cancer patients. HL-GI patients did however receive less treatment with radiation therapy or chemotherapy. These treatments may not have been recommended due to prior Hodgkin lymphoma treatment or comorbidity. As risks of other causes of mortality are also increased in Hodgkin lymphoma survivors, the relatively good survival in this population is remarkable.

7504Background: Rituximab (R)-CHOP is standard treatment for patients with diffuse large B-cell lymphoma (DLBCL). The optimal R dose and schedule is not known. We compared R-CHOP-14 with the same r...

9517 Background: HL treatment is associated with high risk of treatment-related morbidity, including second cancers and cardiovascular diseases. However, only few studies examined excess mortality ...

8039 Background: During the last decades Hodgkin Lymphoma (HL) treatment changed towards less toxic chemotherapy schemes and smaller radiation fields. The impact of these changes on second cancer (SC) risk is still unknown. Methods: We calculated standardized incidence ratios (SIR), comparing SC risk after HL treatment with expected risk, based on cancer incidence in the general population, and compared SC risk between treatment modalities, accounting for competing events, in a large Dutch cohort comprising 3,390 5-years HL survivors, aged 15-51 years at HL treatment and diagnosed between 1965-2000. Results: The median follow-up was 18.2 years; 23% of the patients was followed ≥25 years. During follow-up 734 SCs and 92 third cancers (TC) occurred. The SIR for any SC was 4.5 (95% confidence interval (95%CI) 4.1-4.9). SC risk was still elevated after 35 years of follow-up (SIR 3.9; 95%CI 2.5-5.8) and cumulative incidence (CI) reached 47.1% (95%CI 43.6-50.5) at 40 years follow-up. For TCs the SIR was 5.5 (95%CI 4.4-6.9); the 20-year CI was 22.3% (95%CI 17.8-27.2). Risks of NHL and leukemia strongly decreased in more recent treatment periods (P-trend 4.2 g/m2 yielded a 1.3-fold increased HR (95%CI 1.0-1.7) for non-breast STs and a 2-fold (95%CI 1.2-3.1) increased HR for gastrointestinal STs, but was associated with a strongly decreased BC risk (HR 0.3, 95%CI 0.2-0.6). Conclusions: SC risk after HL has decreased with treatment changes over the last decades, due to strongly decreasing risk of leukemia and NHL. Smaller radiation fields and procarbazine doses >4.2 g/m2 are associated with lower breast cancer risk, while high procarbazine doses increase risk of gastrointestinal STs.