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8565 Background: Although HDAC-containing CTX with rituximab (R) followed by high-dose CTX (HDC) with autologous stem cell transplantation (ASCT) has been recommended in younger untreated MCL patie...

6533 Background: Although allogeneic stem cell transplantation (allo-SCT) could improve the outcome of adult Philadelphia chromosome-negative acute lymphoblastic leukemia [Ph(-) ALL], the impact of the donor source, particularly the position of cord blood (CB) transplantation, is still uncertain. Methods: We retrospectively analyzed 1726 adult Ph(-) ALL patients transplanted at the first time between 1998 and 2009 with myeloablative preparative regimens who were registered in the Japan Society for Hematopoietic Cell Transplantation database. Two hundred and thirty-three received CB transplantation [first complete remission (CR1): 95, subsequent CR: 53, non-CR: 85], 809 received allo-SCT from unrelated donor (URD) (CR1: 434, subsequent CR: 158, non-CR: 217), and 684 received allo-SCT from related donor (RD) (CR1: 388, subsequent CR: 89, non-CR: 207). Results: Overall survival (OS) in patients after CB transplantation in CR1 was comparable with that after allo-SCT from URD or RD [57% in CB, 64% in URD, and 65% in RD at 4 years, respectively, P=0.11]. Donor source was not a significant risk factor for OS in multivariate analysis. Although URD was a favorable factor for relapse and an unfavorable factor for non-relapse mortality (NRM), CB was not a significant factor for them [Relapse: 22% in CB, 17% in URD, and 24% in RD at 3 years, respectively (P=0.02); NRM: 27% in CB, 23% in URD, and 13% in RD at 3 years, respectively (P=0.0001)]. Among CB recipients in CR1, age at allo-SCT (45 years or older) was solely a significant adverse prognostic factor in multivariate analysis. Among patients younger than 45 years who received allo-SCT in CR1, OS after CB transplantation was significantly better than that after allo-SCT from mismatched URD (4-year OS: 68% vs. 49%, P=0.04). Similarly, OS was not different by donor source in subsequent CR or non-CR [Subsequent CR: 48% in CB, 39% in URD and 48% in RD, P=0.33; non-CR: 18% in CB, 21% in URD, and 15% in RD, P=0.20 at 4 years, respectively]. Conclusions: Allo-SCT using CB led to similar outcomes as either RD or URD in any disease status. CB transplantation is a good alternative for adult Ph(-) ALL patients without a suitable RD or URD.

8616 Background: R-CHOP is regarded as one of the most effective initial treatments for indolent B-cell Non-Hodgkin lymphoma (B-NHL); however, the information on its long term outcome is limited. Methods: Sixty-nine patients (pts) with untreated indolent B-NHL of advanced stages were randomized in the concurrent or sequential combinations of R-CHOP. Pts in the concurrent arm (Arm C) received 6 times of R (375 mg/m2), 2 days prior to each cycle of CHOP, and pts in the sequential arm (Arm S) received weekly 6 times of R (375 mg/m2) following 6 cycles of CHOP. No maintenance therapy was given in both arms. The last pt was enrolled in July, 2000, and the planned observation was completed in May, 2007. Results: A total of 69 pts were randomized but 2 were withdrawn before receiving treatment because of neutropenia or concomitant cancer. Sixty-five pts (94%) had follicular lymphoma, and 31 pts were in low, 27 in intermediate and 11 in high risk group according to the Follicular Lymphoma International Prognostic...

18521 Background: Vorinostat (Zolinza™), a potent histone deacetylase inhibitor, has demonstrated clinical activity in pts with cutaneous T-cell lymphomas (CTCL) and other NHL subtypes. However, the clinical activity and PK profile in Japanese pts with NHL was unknown. Methods: Japanese pts with NHL were sequentially enrolled in two dose levels ranged from 100 (Level 1) - 200 mg (Level 2) BID, PO for 14 consecutive days every 3 wks. Higher doses were not tested as other phase I studies had established that 300 mg BID for 14 consecutive days every 3 wks exceeded the MTD. PK profiles were analyzed in serum and urine samples. Response was also evaluated according to the international workshop criteria. Results: Ten pts were enrolled: 9 were evaluable for toxicity. One was excluded due to noncompletion of the 1st cycle. All were evaluable for PK. Median age was 60 yrs (range 52–74). Four pts had follicular lymphoma (FL), 2 mantle cell lymphoma (MCL), 2 diffuse large B-cell lymphoma and 2 CTCL. Median no. of prior regimens was 3 (1–4). In the 1st cycle, none of 3 pts at Level 1 and 1 of 6 pts at Level 2 developed DLTs (anorexia and hypokalemia of grade 3), indicating Level 2 to be the MTD in this setting. PK was not greatly affected by multiple doses. Intact drug was hardly excreted in urine ( No significant financial relationships to disclose.

17515 Background: Dasatinib is a potent, orally active, multi-targeted kinase inhibitor of BCR-ABL and SRC family kinases. Studies outside Japan have shown dasatinib to be highly effective in overcoming resistance and intolerance to imatinib, inducing durable cytogenetic (CyR) and hematologic responses (HR) in this population. The maximum tolerated dose was not reached in the Phase-I trial outside Japan and a 70-mg BID dose was determined to provide the optimal benefit-risk profile. Methods: This Phase-I/-II study was designed to assess the safety and efficacy of dasatinib in Japanese patients with imatinib-resistant or -intolerant CML or Ph+ALL. In the 4-week Phase-I portion in patients with chronic-phase (CP) CML, three dose levels were evaluated: 50 mg, 70 mg, and 90 mg BID. The Phase-II portion is currently evaluating the CyR of dasatinib in patients with CP-CML at 24 weeks, and the HR rate in accelerated- (AP) or blast-phase (BP) CML and Ph+ ALL at 12 weeks. Results: As of December 2006, 17 eligible patients have been treated in Phase I. Six patients (4F, 2M; median age 43 y [range 27–56]) were treated with 50 mg BID and 1 dose-limiting toxicity (DLT) was observed (Grade 4 thrombocytopenia). Two patients experienced transient Grade 3 ALT elevations but as treatment was uninterrupted, these were not considered DLTs. Six patients (6M; median age 42 y [range 27–55]) were treated with 70 mg BID and again 1 DLT was observed (Grade 4 thrombocytopenia). No DLT has been observed among 4 patients (3M, 1F; median age 41 y [range 27–64]) at the 90-mg BID dose. Major CyRs have been achieved in all three cohorts in the Phase-I segment of the trial. Thirty six patients were enrolled and treated in the Phase-II part of the trial (12 CP-CML, 7 AP- CML, 4 BP-CML, and 13 Ph+ALL). Efficacy and safety data as well as the baseline BCR-ABL mutation data are currently being assessed and will be presented. Conclusions: Dasatinib can be safely administered at doses of up to 90 mg BID to Japanese patients with imatinib-resistant or -intolerant CP-CML. No significant financial relationships to disclose.

8566 Background: Rasburicase (RAS) for the prevention of tumor lysis syndrome (TLS) populations at high risk, and for the treatment of hyperuricemia (HU) has obtained approvals in most countries in the world except in Japan. Thus, we conducted licensing phase II study of RAS with primary endpoint of overall efficacy response (ER) rate. We report efficacy and the new safety profile of only RAS administration prior to chemotherapy. Methods: Fifty patients (pts) with ML and/or AL, were administered RAS for 5 days using two dose-levels (0.15 mg/kg/day or 0.20 mg/kg/day). Chemotherapies were started from 4 to 24 hours after RAS treatment. ER was defined as keeping plasma uric acid level 7.5mg/dL by 48 hr after the start of first RAS infusion and lasting until 24 hr after the start of final (Day5) RAS infusion. Results: The overall ER rate was 98%. 49 pts (98%) completed 5 days of treatment. Both doses provided equally effective reduction of uric acid under the study conditions. Seven drug-related adverse events of grade 1 or 2 by NCI-CTC occurred in 6 pts during using only RAS (before first chemotherapy). ‘Hypersensitivity’ occurred in 3 pts, and ‘rash’, ‘anorexia’, ‘application site pain’, and ‘pyrexia’ occurred in 1 patient each. No grade 3 or 4 adverse events were reported. Only five pts (10%) had anti-RAS antibodies by Day29. Conclusions: RAS has proved to be highly effective with a good safety profile including the new safety one as single agent without chemotherapy. Although both two levels were effective, level of 0.20 mg/kg seems to be an optimal dose because RAS was effective against serious cases of HU in this level. The presence of anti-RAS antibodies was very low suggesting that the possibility for retreatment maybe possible. No significant financial relationships to disclose.

6577 Background: R-CHOP is regarded as the best available treatment for untreated patients (pts) with indolent and aggressive B-NHL; however, the optimal combination schedule in indolent B-NHL remains unknown. Methods: Previously untreated pts with indolent B-NHL of advanced stages were randomly allocated to the concurrent arm (Arm C) or the sequential arm (Arm S). All pts received 6 cycles of standard CHOP every 3 weeks. In addition, Arm C received R at 375 mg/m2, 6 times, 2 days prior to each cycle of CHOP, whereas Arm S received R at 375 mg/m2, weekly 6 times, following 6 cycles of CHOP. Pts were monitored for clinical response by the International Workshop Criteria, molecular response by PCR assay for bcl-2 rearrangement in bone marrow and peripheral blood, and adverse events for at least 3 years or until progression. The primary endpoint was the overall response rate (ORR). Results: Between July 1999 and July 2000, a total of 69 pts were enrolled, and 66 (Arm C, 32; Arm S, 34) of them were eligible. ...

6704 Background: Optimal combination schedule of R-CHOP for untreated FL is still uncertain. Quantitative evaluation of MRD may suggest a correlation between the treatment schedule and its outcome. Methods: We conducted a randomized phase II study comparing 6 cycles of R-CHOP (concurrent; Arm C) and 6 cycles of CHOP followed by weekly 6 doses of rituximab (sequential; Arm S) for previously untreated, advanced-stage indolent B-cell lymphoma, mainly consisting of FL. DNA of bone marrow (BM) and peripheral blood (PB) were obtained before treatment (baseline), after 3 cycles and 6 cycles of R-CHOP/CHOP, and 4 months after R-CHOP/CHOP followed by rituximab (4 mo). Bcl-2/JH translocation was amplified and quantified by real-time PCR. Results: Sixty-five (94%) of 69 enrolled patients (pts) were diagnosed as having FL by the central pathology review. Bcl-2(MBR)/JH translocation in BM and/or PB were detectable in 27 pts (14 pts in Arm C and 13 pts in Arm S). Faster decrease in bcl-2/JH copy numbers, and thus highe...