The responses of arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia / 白血病·淋巴瘤

Objective To analysis long-term effects and safety of arsenic trioxide (ATO)-based induction and maintenance therapy in newly diagnosed acute promyelocytic leukemia (APL). Methods Retrospective analysis induction remission and post-remission treatment of 62 newly diagnosed APL patients was performed. These cases were followed up for 5 and 7 years. Results The complete remission (CR) rate was similar in ATO/all-trans retinoic acid (ATRA) induction group and ATRA/chemotherapy induction group.However, the former group has the shorter time to CR. The negative rate of PML-RARα fusion gene after induction without ATO was less than that of ATO group (86.2 % vs 56.3 %, P ＜0.05). After CR, the 5-year overall survival (OS) between ATO-base rotation maintenance group and chemotherapy-base rotation maintenance group showed that the former was (94.4±5.4) %, the latter is (45.5±10.2) %; 7-year OS was (52.5±23.7) % and (27.3±9.3) %; 5-year disease free survivals (DFS) was (94.7±5,5) % and (41.3±10.1) %; 7-year DFS was (52.6±23.7) % and (27.5±9.4) %. There was significant different in 5-year or 7-year OS and DFS between two groups (P ＜0.05). The relapse rates of the two groups in post-remission treatment were 14.7 % and 37.0 % (P ＜0.05). Conclusion ATO combined ATRA induction therapy increased the negative rate of PML-RARα fusion gene. ATO-base rotation maintenance improved long-term outcome and decreased the rate of relapse. Furthermore, ATO appeared to be generally safe and well tolerated.

Outcomes and survival analysis of patients with AML and high risk MDS treated by CAG regimen / 上海交通大学学报（医学版）

Objective To evaluate the clinical efficacy and adverse effects of CAG regimen in treatment of primary, refractory and relapsed acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS), and analyse the factors influencing long-term survival. Methods Sixty-one patients with AML ( primary, n = 27; refractory, n = 18; relapsed, n = 16) and 9 patients with MDS were treated with CAG regimen. Examinations on liver and renal function, electrocardiogram and bone marrow cytology were performed before and after treatment, and adverse effects of CAG were observed. Short-term efficacy was evaluated based on clinical manifestation, peripheral blood and bone marrow cytologic examinations. Patients were followed up, overall survival ( OS) and disease free survival ( DFS) were analysed, and long-term efficacy of CAG regimen was evaluated. The factors influencing long-term survival were analysed by Log-rank test of survival curve. Results After a course of treatment by CAG regimen, the total effective rate was 71% , and 34 patients (49%) experienced complete remission. The median time of follow up was 45 months, the median OS was 28 months, and the median DFS was 23 months. Age, level of lactate dehydrogenase (LDH), remission condition after a course of treatment by CAG regimen and adoption of HD-Ara-C regimen as consolidation treatment were influencing factors for OS and DFS. The dominant clinical adverse effects were bone marrow depression, with 13 d as the median duration of agranulocytosis ( neutrophil <0.5 ×10~9/L) and 9 d as the median duration of thrombocytopenia (platelet <20 ×10~9/L). Conclusion CAG regimen may lead to favourable therapeutic effects in treatment of primary, refractory and relapsed AML and high risk MDS, and may yield less adverse effects and better long-term therapeutic effects. Age, level of LDH, remission condition after a course of treatment and adoption of HD-Ara-C regimen as consolidation treatment are dominant influencing factors for survival.

Effects of red orpiment on cell morphology and expression of PML mRNA and protein in NB4 and HL-60 cells / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effects of red orpiment on cell morphology, expression of promyelocytic leukemia (PML) mRNA and its protein localization in NB4 and HL-60 cell lines.</p><p><b>METHODS</b>Cell morphology was assayed by Wright's staining and fluorescence staining, while PML mRNA expression was determined by RT-PCR. PML protein localization by evaluated by immunofluorescence staining.</p><p><b>RESULTS</b>The typical apoptosis was found in NB4 and HL-60 cells after treatment with red orpiment. The fusion protein was no longer observed in NB4 cells, PML protein was relocated, and then degraded. In HL-60 cells, PML protein underwent a similar progress. The expression of promyelocytic leukemia (PML) mRNA was not changed in the treated cells.</p><p><b>CONCLUSION</b>Red orpiment inhibits the proliferation of leukemia cells by inducing them to undergo apoptosis.</p>

Study on gene expression changes of arsenic sulfide treated NB4 cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the gene expression status of NB4 cells before and after arsenic sulfide treatment by cDNA microarray.</p><p><b>METHODS</b>Two cDNA probes were made from mRNA of untreated or arsenic sulfide treated NB4 cells. The cells were labelled with Cy3 or Cy5 fluorescence dyes individually, hybridized with cDNA microarray, and scanned for fluorescent intensity. The altered gene expression was screened through the analysis of difference in gene expression profile.</p><p><b>RESULTS</b>Thirty four genes related to apoptosis, cell cycle and others expressed different after the treatment of arsenic sulfide, 28/34 were up-regulated, 6/34 down-regulated.</p><p><b>CONCLUSION</b>ABC50, PNAS-2 and cyclin G(2) might take part in the process of NB4 cell apoptosis induced by arsenic sulfide.</p>

Study of the effects of quercetin on PML gene and protein expression and localization in leukemia cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate PML gene and protein expression and localization in leukemia cell lines.</p><p><b>METHODS</b>Cell morphology was assayed by Wright and fluorescence stain, PML mRNA expression by RT-PCR, and PML protein localization by immunofluorescence.</p><p><b>RESULTS</b>(1) Differentiation was observed by morphology in NB4 and HL-60 cells after treatment with all-trans retinoic acid (ATRA) while K562 cells did not show. Apoptosis was found in each cell line after treatment with quercetin. (2) After treatment with ATRA, the fusion protein disappeared and PML protein resumed in NB4 cells, while in HL-60 and K562 cells there was no difference from control cells. After treatment with quercetin, the fusion protein disappeared in NB4 cells, then degraded, and so did in HL-60 cells and K562 cells. (3) The expression of PML mRNA had no change in all the three cell lines after treatment with ATRA or quercetin.</p><p><b>CONCLUSION</b>PML plays a role of differentiation and apoptosis induction in leukemia cells at the translational level. PML in POD plays a role of apoptosis induction and growth control of leukemia cells.</p>

The clinical efficacy observation of VAD regimen in the treatment of newly diagn osed multiple myeloma / 中国癌症杂志

Purpose: To evaluate the clinical efficacy of V AD regimen in the treatment of newly diagnosed stage III multiple myeloma (MM). Methods:26 patients with newly diagnosed stage Ⅲ multiple myel oma were treated with VAD regimen. VAD solution consisted of vincristine (VCR) , doxorubicin(ADR),dexamethasone (Dex).Three continuous treatments in one treatm ent course were considered evaluable.Evaluation included results of serum myelom a protein(M-protein); renal function; proteinuria of 24-hours; bone marrow ; per ipheral blood et al.The side reactions were recorded. The clinical efficacy eval uation was divide into complete response(CR),partial response(PR),minimal-respon se(MR), no change(NC) , plateau progression.Results:5 cases achieved CR(19.3%), 13 cases PR(50%),6 case s MR (23%), 2 cases no change (7.7%). Overall response rate was 92.3%, median su rvival duration was 7 to 84 months (29.6?17months). Conclusions:Achieved marked clinical efficacy with VAD agent in newly diagnosed stage III multiple myeloma. Especially,the patients with renal failure and serious clinical manifestation improved rapidly and significantly.