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High-dose ifosfamide and mitoxantrone (HDIM) in patients with

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Background: Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease in which red blood cells (RBC) are targeted by autoantibodies confirmed with positive direct antiglobulin test (DAT), resulting in premature destruction of RBC. AIHA may be subdivided into warm antibody AIHA (wAIHA) and cold antibody AIHA (cAIHA), and also to primary and secondary depending on the presence of an underlying disorder. In addition to that, patients may have positive DAT but without features of hemolysis, and some of them will later develop AIHA. Aims: The aim of this study was to analyze characteristics of newly diagnosed DAT positive AIHA patients during the 5 years period in our tertiary center, as well to assess DAT positive patients without features of AIHA. Methods: This was a single-center retrospective cohort study performed

4889 PTCLs, except ALK+ ALCL, have a bad prognosis with overall 5-year survival rates below 30%. Because of their relative rarity, no large randomized trials have been performed and the importance of individual cytotoxic agents, their dose density and intensity as well as that of autografting remains unproven. At our center we have been using dose-intense BACOP, a regimen modeled after the French ACVBP, for treatment of patients with high risk PTCL. The regimen consisted of cyclophosphamide 1500 mg/m2 day 1, doxorubicin 75 mg/m2 day 1, bleomycin 15 mg days 1 and 5, vincristine 2 mg days 1 and 5 and prednisone 50 mg/m2 days1-5 every 3 weeks for 4–6 cycles. Responding patients underwent stem-cell collection and autografting after BEAM conditioning. Areas of initially bulky disease and those not in CR prior to transplantation were irradiated posttransplant with 30–40 Gy. Patients with high risk for development of CNS disease received intrathecal methotrexate prophylaxis. Response evaluations were performed after 2–3 cycles and at the end of chemotherapy. Patients were considered high risk if they had any PTCL type with IPI 3 or more, bulky disease or failed to respond to 2–3 cycles of standard CHOP-21. We treated 28 patients, 20 men and 8 women, 17–67 years old (median 46). Thirteen had PTCL-NOS, 8 ALCL, 3 AILD, 2 nasal type, 1 panniculitis-like and 1 hepatosplenic PTCL. Two had stage IE bulky, 1 stage II bulky, 2 stage III and 23 stage IV disease. The toxicity of treatment was substantial, all patients experienced serious hematological toxicity and infections or neutropenic fever, 3 died of infection during chemotherapy and 1 during stem-cell transplantation, 2 had DVT/PE, 1 died of complications related to the necrosis of an extremely bulky tumor and one underwent emergency splenectomy after tumor necrosis caused splenic rupture. Three patients were unavailable for efficacy analysis due to early death, 4 progressed and 21 initially responded (75%); 14 achieved CR and 7 PR. None of the 3 patients with nasal type or hepatosplenic PTCL responded. Of the responders, 11 underwent autografting as intended, 3 relapsed prior to transplantation, treatment was modified in 3 due to toxicity, 2 were not transplanted due to patient refusal or physician decision, 1 underwent allogeneic transplantation and 1 failed to mobilize. After a median follow-up of survivors of 20 months, 9 patients are still alive, including 8 who were autografted as intended. Median response duration was 12 months, FFS 6 months and OS 9 months (Fig). In conclusion, a significant proportion of high-risk PTCL-NOS, ALCL and AILD patients respond to dose-intense BACOP followed by autologous stem-cell transplantation but the toxicity of treatment is substantial. Disclosures: No relevant conflicts of interest to declare.

2372 Poster Board II-349 Chlorambucil is an effective and safe oral alkylating agent used for treatment of indolent lymphoproliferative disorders. While once considered a drug of choice for CLL, it has recently fallen out of favor, mostly due to clinical trials showing that fludarabine-based combinations have better disease-free, albeit not overall survival (OS). In these studies chlorambucil was administered once every 2-4 weeks. Results of some clinical trials suggest that continuous use of high doses of chlorambucil (≥ 10mg /day) is superior to intermittent administration. However, there are very few publications reporting outcomes of this type of treatment, especially outside of clinical trials. Here we summarize our experience with this approach in unselected patients with CLL. This was a retrospective study performed by chart-review of patients treated at our center. Patients were included in this analysis if they had CLL according to standard immunologic, morphologic and hematologic criteria, were in need of treatment and received chlorambucil at a daily dose of 10 mg or more for at least 4 weeks or until response or unacceptable toxicity as front-line treatment. Simultaneous administration of steroids but not other cytotoxic drugs was allowed. Use of low-dose chlorambucil maintenance (≤ 5 mg/day) after stopping high-dose chlorambucil was not considered treatment failure. The Kaplan-Meier method was used for creating survival curves and log-rank for comparisons of temporal variables. We identified 88 patients fulfilling the inclusion criteria, 70 men and 18 women, who were at the time of treatment start 38-88 years old (median 64). Nineteen patients were in Binet stage A, 38 B and 31 C; 2 were in Rai stage 0, 27 stage 1, 38 stage 2, 6 stage 3 and 25 stage 4. Twenty-nine had a low and 59 high total-tumor-mass index (TTM). The dose of chlorambucil ranged form 10 to 20 mg daily (median 15) and duration of treatment 2 to 20 wks (median 5). Forty-seven patients (53%) also received low-dose chlorambucil maintenance. The treatment was well tolerated. Three patients (3%) had serious infections, 2 died; 5 (6%) had severe hematological toxicity, mostly thrombocytopenia. Nausea, very common with pulse-doses of chlorambucil, was absent or mild; only 1 patient had severe nausea. Sixty-nine patients (78%) responded. After a median follow-up of survivors of 58 months, 26 patients are still alive and 17 have not failed treatment. Median OS was 53 months, 95% confidence-interval (CI) 40-66 months, time to treatment failure (TTF) 20 months (95% CI 13-27) (Fig. 1) and progression-free survival 15 months (95% CI 8-22). Age had no influence on treatment outcome. OS of patients with favorable stages (Rai 0-2, Binet A&B) was 60 months and of those with unfavorable stages 44 months. TTF was 30 and 11 months in these groups respectively. Both of these differences barely failed to reach statistical significance (p=0.067 and 0.058). TTM of 9 or higher was the only statistically significant negative prognostic factor that we were able to identify. OS was 78 vs. 44 months (p=0.021) and TTF 46 vs. 15 months (p=0.027). In conclusion, our results suggest that continuous administration of relatively high doses of chlorambucil is superior to intermittent administration, resulting in better efficacy and lower toxicity. While our results are inferior to those generally reported with fludarabine-based front-line treatments, continuous high-dose chlorambucil is less toxic, cheaper, the duration of treatment is shorter and OS is not different. This makes continuous high-dose chlorambucil an interesting approach for elderly, time- or financially constrained patients or health-care systems. Also, the low-toxicity and short treatment duration make it an interesting platform for the addition of non-toxic targeted drugs, like rituximab. Disclosures: No relevant conflicts of interest to declare.