Sunitinib administered with a 2/1 schedule is associated with less toxicity and higher FFS at 6 months than a 4/2 schedule, without compromising the efficacy in terms of ORR and TTP (NCT00570882).

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The result of cytogenetics is one of the most important prognostic factors on the prognosis of AML. HDAC, auto PBPCT and allogeneic BMT after 1 or 2 times of post remission therapy based on 4 prognostic groups(APL: Acute promyelocytic leukemia, GPG: Good prognosis group, IPG: Intermediate prognosis group, PPG: Poor prognosis group by MRC definition) were underwent based on cytogenetics data. We studied CR, relapse, toxic death, DFS and OS. Inclusion criteria were age<65, PS<3 with reasonable organ functions in de novo AML, secondary AML and RAEB-T. The aims of this prospective intention to treat analysis was to compare the CR, recovery kinetics, DFS and OS by giving different therapies of intensity in the different prognostic groups based on cytogentics data. Three plus seven(Idarubicin 12mg/m2(D1–D3), Ara-C 100mg/m2(D1–D7)) were given to de novo AML, secondary AML and RAEB-T. Intermediate dose(8gm/m2) of Ara-C was given followed by HDAC or auto PBPCT to the patients with GPG(t(8:21) & inv(16)). Three times of post remission therapy including HDAC, or auto PBPCT were given to the patients with IPG or PPG(−5, −7, del 5q, complex). If HLA-identical sibling was available, then allo BMT was underwent after 1st post-remission therapy. In cases of APL, three times of post-remission therapy with idarubicin alone were given. ATRA was given to APL group during remission induction therapy and after post-remission maintenance period for 2 years. Up to Mar., 2005, 422 patients(18 centers) were enrolled. Median follow-up was 48months. Among them, 92.3% was de novo AML, and APL, GPG, IPG and PPG were 10.0%, 21.6%, 51.4%, and 14.7% respectively. Overall CR after 1st induction(3+7) were 69.9%(APL: 87.2%, GPG: 84.7%, IPG: 63.8%, PPG: 55.66%, P<0.01). Relapse rate was 12.8%(APL), 40.5%(GPG), 40.5%(IPG) and 45.6%(PPG) respectively(P<0.01). Toxicities profiles including mucositis, hepatic, cardiac and bleeding episodes were similar on 3 different therapy modalities(HDAC, auto PBPCT and allo BMT). In conclusions, this trial seems to be tolerable in terms of toxicities after induction and during post remission therapies. Among GPG, there were no significant statistical differences on OS and LFS in all the therapy modalities(ie, HDAC, Auto, Allo). In IPG, auto arm had a tendency of superior OS and LFS comparing to HDA & allo arm. In PPG, there was significant surperior LFS in allo arm. There were no statistical differences on OS in all the therapy modalities in PPG. This intention to treattrial, which had started in Jan, 2000, has been going on until now. Through this risk based trial using cytogenetics, we might be able to find optimal post-remission therapies for different risk groups with less toxicities.

Background: Double-protein-expression lymphomas (DEL) is a unique sub-group of diffuse large B-cell lymphoma (DLBCL) with co-expression of MYC and BCL-2 on immunohistochemistry. Compared with classic DLBCL, DEL has a lower response to standard induction chemoimmunotherapy with rituximab added to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and poorer prognosis. Autologous stem cell transplant (ASCT) is a potentially curative treatment of high-risk of relapsed/refractory lymphomas. However, the role of ASCT in patients with DEL is controversy. Our pre-clinic and clinic studies showed the combination of chidamide, cladribine, gemcitabine and busulfan (ChiCGB) worked synergistically against lymphomas. Aims: So, in this study, we used ASCT conditioning with ChiCGB as consolidation in patients with DEL in first or second complete remission. Methods: This study was a phase 2 trial done at the West China Hospital of Sichuan University from May. 2016 to Dec. 2018. Eligible patients were aged 16-65 years and had received R-CHOP or chidamide-R-CHOP as first-line or any second-line therapies. They achieve first or second complete remission (CR) before transplant. The DEL was diagnosed as MYC expression ≥ 40% and BCL-2 ≥ 50% on immunohistochemistry. Additional eligibility criteria were an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, adequate major organs function, no active hepatitis bacteria, fungal or virus infection. Patients provided written informed consent to participate in the trial. Patients with DLBCL without MYC and BCL-2 over-expression were assigned to the control group (non-DEL). Patients received ChiCGB conditioning regimen consisting of oral chidamide 30 mg on days −7, −4, 0, +3, intravenous cladribine at a dose of 6 mg/m 2 from days −6 to −2, intravenous gemcitabine 4 hours after cladribine at a dose of 2500 mg/m 2 on days −6 and −2, and intravenous busulfan at a fixed dose of 3.2 mg/kg from days −6 to −2. Dexamethasone was prophylactically given for adverse effect of high dose gemcitabine from the day −6 to −2. Peripheral-blood stem-cells were infused on day 0.Results: A total of 44 patients with DLBCL were enrolled, with 22 DEL and 22 non-DEL. The median age was 46 (range, 23 to 61) and 34.5 (range, 16 to 61) years in DEL and non-DEL groups. There were 8 (36.3%) and 12 (54.5%) patients in second CR in DEL and non-DEL group respectively. In DEL group, 5 patients receive chidamide-R-CHOP as first-line therapy. Stem cells source was peripheral blood. Median infused CD34+cells count was 2.2 × 10 6 /Kg (range, 1.0 to 11.6 × 10 6 /Kg). Neutrophils and platelets were engrafted on a median day +10 (+8 to +14) and day +12 (range, days +8 to +38), respectively. The median follow-up was 17.8 (range, 4.1 to 34.9) and 20 (range, 3 to 46.3) months in DEL and non-DEL group. The 2-year progression free survival of patients with DEL or non-DEL was 94.4% and 84.2% (P = 0.3731), while the 2-year overall survival of tow groups was 94.1% and 100% (P = 0.2904) (Figure -1). Summary/C...