The risk factors and therapeutic strategies of infection in patients with myelodysplastic syndromes / 天津医药

@#Myelodysplastic syndrome (MDS) is a group of malignant clonal neoplasms originated in hematopoietic stem cells. Due to the continuous low peripheral blood leukocytes, the high-risk patients will also receive the treatment of demethylated drug, chemotherapy and hematopoietic stem cell transplantation. MDS are mostly the elderly, and there is a relatively high risk of infection in patients. It is known that the main cause of infection in MDS patients is neutropenia, in addition, the abnormal lymphocyte subgroups, iron overload, older age, and complications are also related factors of infection. Based on these risk factors, to evaluate the risk of infection, to provide early prevention and optimization of anti-infection treatment strategies can ultimately improve the treatment effect and prolong the overall survival time of the patients

Therapeutic Efficacy of VICP+L-ASP/TKI on Adult Patients with B-ALL / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic efficacy of VICP+L-ASP/TKI on adult patients with B-ALL and to explore the influence factors.</p><p><b>METHODS</b>Forty-one adult B-ALL patients treated with VICP+L-ASP/TKI from August 2008 to June 2014 were following-up. The complete remission(CR) rate, toxicity, overall survival(OS) and event free survival(EFS) after induction treatment were analyzed, the therapeutic outcome of patients between different risk stratification subgroups was compared, the influence of standardized consolidatory and maintaining treatment as well as allogeneic hematopoietic stem cell transplantation(allo-HSCT) on survival time was analyzed.</p><p><b>RESULTS</b>The early death not occurred in 41 patients with B-ALL including 37 cases with CR; the CR rate of 1 course treatment was 90.2%. The follow-up time lasted to March 17, 2015, the median follow-up time was 25(9-79) months; the 1 year OS rate was 75.3%, the EFS rate was 58.3%. Analysis of risk factors showed that the initial WBC count over 30×10/L, LDH over 250 U/L and minimal residual disease(MRD) over 10after treatment were poor prognostic factors. After remission, the standardized consolidatory treatment or allo-HSCT according to the "2012 China adult ALL diagnosis and treatment expert consensus" could improve long-term survival, 3 years OS rate was 73.8% and 61.5% respectively, 3 years EFS were 63.5% and 65.7% respectively. The main toxic and side effects were hematologic reactions, the hematologic adverse reaction of IV grade was observed in 97.6%(40/41) during induction treatment.</p><p><b>CONCLUSION</b>Induction chemotherapy based on VICP+L-ASP/TKI and standardized consolidatory after remission according to the "2012 China adult acute lymphoblastic leukemia diagnosis and treatment expert consensus" can improve the therapeutic efficacy. The allo-HSCT should be actively performed for B-ALL paients with high risk(elevated initial WBC count and LDH level); at some time, the regularly monitoring MRD and adjusting therapeutic protocol according to monitoring result can promote the prognosis of adult B-ALL patients.</p>

Efficacy and safety of the HAA regimen as induction chemotherapy in 236 de novo acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of the HAA regimen (homoharringtonine, cytarabine and aclarubicin) as induction chemotherapy in de novo acute myeloid leukemia (AML).</p><p><b>METHODS</b>The efficacy and safety of 236 de novo AML patients who received the HAA regimen as induction chemotherapy were retrospectively analyzed. The complete remission (CR) rate was assayed. Kaplan-Meier method was used to estimate overall survival (OS) and relapse free survival (RFS), and the differences were compared by Log-rank test.</p><p><b>RESULTS</b>The overall CR rate was 78.0%, and 65.7% of the patients attained CR in the first induction cycle. The early death rate was 4.7%. The median followup time was 41(1-161) months. The estimated 5-year OS and 5-year RFS rates were 44.9% and 45.5%, respectively. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 92.9%,78.6%and 41.7%, respectively. The 5-year OS of favorable and intermediate group were 61.1% and 45.1%, respectively. The 5- year RFS of favorable and intermediate group were 49.0% and 45.4%, respectively. The median survival time of unfavorable group was only 5 months. The side effects associated with the HAA regimen were tolerable, in which the most common toxicities were myelosuppression and infection.</p><p><b>CONCLUSION</b>The HAA regimen is associated with a higher rate of CR and longer survival time and its toxicity could be tolerated.</p>

Clinical study of Philadelphia chromosome-positive adult acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics, risk factors and therapeutic outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia (Ph(+)aALL).</p><p><b>METHODS</b>The clinical data of 117 newly diagnosed adults with Ph(+)ALL in our hospital between January 1995 and December 2009 were retrospectively analyzed. And their prognoses were followed up.</p><p><b>RESULTS</b>There were 117(16.1%) of 727 aALL patients diagnosed as Ph(+)aALL. Among the 117 cases, 64.1% patients were classified as pre-B immunophenotype and 31.3% as common B immunophenotype, 37.5% patients with co-expression of myeloid antigens (CD13 or CD33), and 98.4% patients with positive CD34. The complete remission (CR) rate after 1 or 2 cycles of induction chemotherapy was 62.2% in Ph(+)aALL group versus 82% in Ph(-)aALL group (P = 0.000). The median disease-free survival time of Ph(+) group was 6 months and the median survival time was 9 months. Sole karyotype abnormality subgroup t(9;22) accounted for 53% of all Ph(+)aALL patients and additional karyotype abnormality subgroup, t(9;22) plus other chromosome variation, accounted for 47%. Patients in sole karyotype abnormality subgroup had slightly lower CR rate (59.6% vs 62.5%, P = 0.768), longer median survival time (7 months vs 4 months, P = 0.158), and higher 3-year overall survival rate (27.3% vs 14.4%, P = 0.271). For the myeloid antigen co-expressed patients and the only lymphocytic antigen expressed ones, CR rate was 56.0% and 61.5% (P = 0.750), the median survival time was 5 months and 4 months (P = 0.182), and the 3-year overall survival rate was 16.0% and 15.0% (P = 0.354), respectively. In the imatinib plus combination chemotherapy treatment group, 81.3% patients achieved CR, compared with that of 58.3% in patients treated with only traditional combination chemotherapy (P = 0.083). The median survival time was 9.5 months and 6 months (P = 0.003) in these two subgroup, and 3-year overall survival rate was 52.2% and 10.3% (P = 0.029), respectively. For the patients receiving allo-HSCT after CR and that receiving traditional consolidation chemotherapy, the median survival time was 15 months and 6 months (P = 0.000), and the 3-year overall survival rate was 62.0% and 10.3% (P = 0.000), respectively. For the patients receiving imatinib as consolidation-maintenance treatment and that receiving allo-HSCT, the median survival time was 12 months and 15 months (P = 0.300), and the 3-year overall survival rate was 64.7% and 62% (P = 0.505), respectively.</p><p><b>CONCLUSION</b>Of all adult ALL patients, the Ph(+) subgroup accounted for about 16.1%, which have unfavorable prognosis such as lower CR rate and shorter survival duration under traditional chemotherapy. Neither additional chromosome abnormalities to t(9;22) nor co-expression of myeloid antigen had negative effect on CR rate and survival duration. Addition of imatinib to the therapy was beneficial to improve the CR rate and survival duration. Either receiving imatinib as consolidation-maintenance treatment or allo-HSCT after complete remission can improve long-term survival rate of Ph(+) adult ALL group significantly.</p>

Effect of homoharringtonine combined with AG490 on JAK2-STAT5 associated signal pathway in HEL cells / 中国实验血液学杂志

This study was aimed to explore the effect of homoharringtonine in combination with AG490 on JAK2-STAT5 associated signal pathway in HEL cells, and analyze its mechanism so as to provide theoretical basis for therapy of chronic myeloproliferative neoplasma by new program. The cell survival rates were tested by MTT, apoptosis was tested by flow cytometry after HEL cells were treated by 20 ng/ml HHT, 100 µmol/L AG490 and 20 ng/ml HHT in combination with 100 µmol/L AG490, while the signal proteins such as P-JAK2, P-STAT5 and BCL-xL activated by abnormal activated JAK2 were tested by Western blot. The results showed that both HHT and AG490 could inhabit the HEL cell proliferation after being treated for 24 hours, and Annexin V-PI double staining confirmed early apoptosis while HHT effect was more obvious, Western blot showed that the expressions of P-JAK2 and P-STAT5 were down-regulated, while the total protein levels of JAK2 and STAT5 were stable. It is concluded that HHT combined with AG490 can obviously inhibit the proliferation and induce early apoptosis of HEL cells, and there is synergistic effect between the two drugs. HHT possibly acts as a broad-spectrum PTK inhibitor and synergistically with AG490 inhibits the phosphorylation of signal proteins caused by JAK2V617F, thus down-regulating the transcription of STAT5.

HAA regimen as induction chemotherapy for newly diagnosed acute myelogenous leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the outcome of newly diagnosed adult acute myeloid leukemia (AML) patients treated with HAA (homoharringtonine, cytarabine and aclarubicin) regimen and explore the efficacy and safety of this regimen.</p><p><b>METHODS</b>Eighty patients were treated with HAA regimen. The complete remission (CR) rate was observed. Kaplan-Meier method was used to estimate relapse free survival (RFS) rate and the differences were compared with 2-sided log-rank test.</p><p><b>RESULTS</b>Of the 80 patients, 65 (81%) attained CR and the CR rate after the first course of induction was 75%. For the CR patients, the median follow-up was 26 (2 -69) months, and the estimated 3-year overall survival (OS) rate was 51% and the estimated 3-year RFS was 53%. For the AML-M5 and AML-M /M2 patients the CR rate was 74% and 87% and 3 year RFS of CR patients was 75% and 37%, respectively. The CR rate of 100%, 83% and 20% was achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. The 3 year OS for favorable and intermediate group was 76% and 50% respectively. The median survival time of unfavorable group was only 6 months.</p><p><b>CONCLUSION</b>HAA regimen is a safe, efficacious, and well-tolerable induction therapy for newly diagnosed AML.</p>

Clinical study of amphotericin B in the treatment of invasive fungal infection in 111 hematological disorder patients with neutrocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the differences in clinical therapeutic effect and safety between amphotericin B and its liposome form in treating invasive fungal infection (IFI) in hematological disorder with neutrocytopenia.</p><p><b>METHODS</b>Of 111 patients with IFI, 82 were treated with amphotericin B and 29 with amphotericin B liposome. The mean cumulative dose of amphotericin B was 617 (60-1895) mg and the mean course was 18 (7-60) d, and those for amphotericin B liposome was 925 (140-3420) mg and 13 (7-50) d, respectively.</p><p><b>RESULTS</b>The total effective rates of amphotericin B and its liposome groups were 69% and 58%, respectively (P>0.05). The adverse effect rates of chill and fever in amphotericin B and its liposome groups were 21% and 10% (P>0.05), hypopotassemia 34% and 14% (P=0.03), hepatic impairment 22% and 17% (P>0.05), and renal impairment 9% and 3%, respectively (P>0.05).</p><p><b>CONCLUSION</b>The therapeutic effect for IFI of amphotericin B and its liposome was similar. The severe adverse reaction of amphotericin B liposome was slightly lower than that of amphotericin B.</p>

Study on the mechanisms of telomerase regulations during apoptosis of the human MDS-RAEB cell line MUTZ-1 cells induced by arsenic trioxide / 中国实验血液学杂志

To investigate the mechanisms of the telomerase regulations during the apoptosis of the human MDS-RAEB cell line MUTZ-1 cells induced by arsenic trioxide (As(2)O(3)), telomerase activity was detected by TRAP-ELISA and the expressions of mRNAs of hTERT, TRF1 (TTAGGG repeat binding factor 1), TRF2 (TTAGGG repeat binding factor 2), bcl-2, and bax genes were detected by RT-PCR. Apoptosis was detected by translocation of phosphatidylserine (PS) by flow cytometry. The results showed that 1 - 8 micromol/L of As(2)O(3) induced typical apoptosis of MUIZ-1 cells in the dose-and time-dependent manners, the telomerase activity could be down-regulated at this concentration and negatively correlated with increased apoptosis (r = -0.938, P = 0.018). The expression of telomerase activity was positively related to the expression of hTERT (r = 0.783, P = 0.022), but As(2)O(3) had no effect on the mRNA expression of TRF1 and TRF2 genes. The inhibition of telomerase activity by As(2)O(3) on MUTZ-1 cells was accompanied with the low expression of bcl-2 gene and the decrease of bcl-2/bax ratio. It is concluded that the apoptosis of MUTZ-1cells induced by As(2)O(3) may occur via the inhibition of telomerase activity and down-regulation of the expression of hTERT mRNA, and this may be one of the mechanisms inducing apoptosis in MUTZ-1 cells treated by As(2)O(3).

Effect of 5-aza-2'-deoxycytidine on cell of high-risk patients with myelodysplastic syndrome in vitro / 中国实验血液学杂志

To investigate the effect of 5-aza-2'-deoxycytidine (5-Aza-CdR) on cell of high-risk patients with myelodysplastic syndrome (MDS) in vitro, the growth inhibition of MUTZ-1 cell induced by 5-Aza-CdR was detected by MTT method; apoptosis was detected by morphological observation and translocation of phosphatidylserine (PS) was examined by flow cytometry assay; the expressions of P15INK4B, DNA methyltransferases (DNMT)(1), DNMT(3A) and DNMT(3B) gene on mRNA level were detected by RT-PCR; methylation of p15INK4B gene in MUTZ-1 cells was detected by PCR using methylation specific primer (MSP). The results showed that 5-Aza-CdR inhibited the growth of MUTZ-1 cells. The IC(50) values of 24, 48 and 72 hours were 6.75, 2.82 and 5.45 mmol/L respectively. Characteristic changes of apoptosis emerged in MUTZ-1 cells after being exposed to 5-Aza-CdR in the different concentration from 0.8 mmol/L to 3.2 mmol/L, and the positive cells of annexin V on the membrane of MUTZ-1 cells were analyzed by flow cytometry. 5-Aza-CdR could activate the p15INK4B gene expression in MUTZ-1 cells by demethylation of the p15INK4B gene in a dose-dependent manner after the cells were treated for 48 hours. Furthermore, 5-Aza-CdR could significantly down-regulate the expressions of DNA methyltransferase genes DNMT(3A) at mRNA level in a dose dependent manner. However, it had no effects on DNMT(1) gene and DNMT(3B) gene. It is concluded that 5-Aza-CdR can inhibit the growth of MUTZ-1 cells and induce the apoptosis of these cells within the range of concentration from 0.8 mmol/L to 3.2 mmol/L, which may be one of the mechanisms of antitumor effects of 5-Aza-CdR. The drug can activate the expression of p15INK4B gene in MUTZ-1 cells by demethylation of the p15INK4B gene through inhibiting the expression of DNMT(3A) gene. It may be the mechanism of 5-Aza-CdR in the treatments of MDS.

Inhibition effect of arsenic trioxide on the growth of human MDS cell line MUTZ-1 cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the inhibition effect of arsenic trioxide (AS(2)O(3)) on the growth of human MDS-RAEB cell line MUTZ-1 cells and to explore the possible cellular and molecular mechanisms.</p><p><b>METHODS</b>The apoptosis and differentiation of MUTZ-1 cells induced by AS(2)O(3) solution of different concentrations were studied with cell morphology, MTT, DNA fragmentation assay, RT-PCR, Nitroblue tetrazolium (NBT) reduction method and flow cytometry.</p><p><b>RESULT</b>(1) Low concentration ofAS(2)O(3) (0.05 - 0.25 micromol/L) had no marked growth inhibition effect on MUTZ-1 cells; after 14 d treatment, it down-regulated the expression of positive cell differentiation antigens CD38, CD7, CD10, HLA-DR (P<0.05), but did not up-regulate the expression of CD11b (P>0.05). (2) After treatment with 1.0 - 20.0 micromol/L of AS(2)O(3), MUTZ-1 cells presented typical features of apoptosis with a dose dependent manner (r=-0.999, P<0.05). The expression of bcl-2 mRNA and the ration of bcl-2/bax were decreased after AS(2)O(3) treatment (P<0.05).</p><p><b>CONCLUSION</b>Low concentration of (2)O(3) may have partial differentiation inducement on MUTZ-1 cells. With a certain range of dose (1.0 - 20.0 micromol/L), (2)O(3) can induce apoptosis of MUTZ-1 cells. (2)O(3) can significantly down-regulate bcl-2 and it might be one of the mechanisms of (2)O(3) treatment.</p>