[Treatment of Ph-adult acute lymphoblastic leukemia patients with Tongji-96 regimen].

OBJECTIVE: To investigate the efficacy and side effects of the consecutive chemotherapeutic protocol, Tongji-96, for adult patients with Philadelphia chromosome negative acute lymphoblastic leukemia (Ph-aALL). METHODS: A retrospective analysis was conducted on 95 cases of Ph-aALL patients treated between January 2004 and December 2012 with Tongji-96 regimen in Tongji hospital, Shanghai. RESULTS: Among these 95 patients, the overall complete remission (CR) rate was 92.6%, 7-year overall survival (OS) and event-free survival (EFS) rates were (39.3±5.9)% and (31.5±5.3)%, respectively, with the median survival of 28 months. Based on multivariable COX proportional hazards regression model analysis, patients with the poor karyotype and failed to achieve CR after first course induction therapy had a higher risk of mortality compared to those who had good or normal cytogenetics and achieved CR after 1 course of induction treatment [the risk ratios (RR) were 3.380 (95% CI 1.530-7.463, P=0.003) and 3.005 (95% CI 1.522-5.933, P=0.002)，respectively]. By means of Kaplan-Meier analysis and Log-rank test，patients aged less than 60 years and successively achieved CR after first induction therapy had more favorable 7-year OS and EFS rates. Patients with normal karyotype and hyperdiploidy had significantly higher 2-year OS and EFS rates compared with those with complex karyotype, t(4;11) translocation and other karyotypes. CONCLUSION: Age (60 years as the cut-off)，treatment courses for achieving CR and cytogenetics were predictive factors for the prognosis of Ph-aALL from this retrospective study. As a comprehensive and sequential therapy protocol, Tongji-96 regimen was proved to obtain long-term survival, reduce risks for relapse and improve outcomes for part Ph-aALL patients.

Sequential arabinosylcytosin with or without fludarabine in paracmastic patients with acute myeloid leukemia.

The purpose of this study is to assess how fludarabine (Fa) influences arabinosylcytosin's (Ara-C) mode of action. Plasma, cerebrospinal and urine samples were withdrawn from two study groups at specific time points and analyzed by HPLC. Group A was treated with Ara-C only whereas Group B was treated with Fa+Ara-C. The two study groups are all undergoing complete remission (CR). The Ara-C dose for Group A was 3g/m2 x 2, and the AUC(0-4) was 5.131 +/- 0.936. The Ara-C dose for Group B was 2g/m2 x 2, and the AUC(0-4) was 12.245 +/- 3.863. The AUC(0-4) for Group B is more than twice the AUC(0-4) for Group A, and these results indicate that Fa conduces a synergistic increase in the concentration and AUC of Ara-C in plasma and in cerebrospinal fluid. The pharmacokinetics between the different dose treatments was statistically different (P = 0.016). The differences in the ratios of C(Ara-u) to C(Ara-C), and in the Tmax between Groups A and B could indicate whether or not Ara-C combined with Fa. Although Group B demonstrates a higher AUC(0-4) with lower doses of Ara-C (2 g/m2 x 2), the adverse drug reaction (ADR) and bone inhibition were not more pronounced in Group B compared to Group A. These results are based on a limited number of case studies, hence, additional studies are necessary to support and prove this hypothesis.

[Study of hypermethylation of SOCS gene in typical myeloproliferative disease].

OBJECTIVE: To investigate the clinical role of hypermethylation of suppressor of cytokine signaling (SOCS) on typical myeloproliferative disease (MPD) patients and its mechanism. METHODS: Methylation specific PCR was used to detect SOCS1, 2, 3 methylation, direct DNA sequencing was performed to detect JAK2V617F mutation, real-time fluorescence quantitative PCR were applied to evaluate transcriptional activity of SOCS1, 2, 3. RESULTS: Among 100 MPD patients, hypermethylation of SOCS1 was detected in 27 (27%), hypermethylation of SOCS2 in 9 (9%), hypermethylation of SOCS3 in 34 (34%); JAK2V617F mutation in 64 (64%). Hypermethylation of SOCS1, 3 greatly inhibited gene expression compared with unmethylated ones (P < 0.05). Presence of JAK2V617F mutation markedly down-regulated SOCS1, 3 gene mRNA expression compared with wild JAK2V617F (P < 0.05). CONCLUSION: Hypermethylation of SOCS1, 3 and JAK2V617F mutation exist in MPD, which inhibited SOCS1, 3 gene expression. SOCS hypermethylation and JAK2V617F mutation can activate JAK-STAT signaling pathways, these observations may provide a potential therapeutic direction.

[Efficacy of DICE (dexamethasone, etoposide, ifosfamide, and cisplatin) regimen on recurrent and refractory non-Hodgkin's lymphoma].

BACKGROUND & OBJECTIVE: There is no standard salvage regimen for patients with recurrent and refractory non-Hodgkin's lymphoma (NHL) so far. This study was to investigate the efficacy of DICE (dexamethasone, isofosfamide, cisplatin, and etoposide) regimen on recurrent and refractory NHL, and observe the adverse events. METHODS: Clinical records of 80 patients with recurrent and refractory NHL, who failed to get remission from CHOP regimen (cyclophosfamide, vincristine, and donaurubicin) and accepted DICE as a salvage regimen for 6 cycles, were reviewed. Of the 80 patients, 25 were T-cell original, and the other 55 were B-cell original. The efficacy of DICE regimen and adverse events were evaluated. RESULTS: The total response rate (RR) of these 80 patients was 56.3%. The complete remission (CR) rate was 27.5%.The total response rate was 48.0% for T-cell NHL and 60.0% for B-cell NHL. The CR rate was 16.0% for T-cell NHL and 32.7% for B-cell NHL. Myelosuppression, nausea, vomit, alopecia, and electrolytes disorder were major adverse events, and could be cured after treatment. No chemotherapy-related death occurred. CONCLUSION: DICE regimen is effective in treating recurrent and refractory NHL.