Advance in the Treatment of Ph Chromosome Positive Acute Lymphoblastic Leukemia ---Review / 中国实验血液学杂志

Abstract　　The curative efficacy of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL) has been improved substantially with the introduction of tyrosine kinase inhibitors (TKIs). However, there is no consensus so far on the following issues, which TKIs should be chosen in combination with chemotherapeutic regimens; which regimen of intensive chemotherapy incorporated into TKIs would be more beneficial to patients. The prognosis of the patients with Ph ALL has been so significantly improved by the combinatorial treatment of TKIs and chemotherapy, thus it is necessary to reevaluate the role of allogeneic hematopoietic stem cell transplantation in the management of Ph ALL. In addition, immunotherapy has achieved an initial success in the treatment of Ph ALL. In this review, the treatment paradigms for the disease are summrized briefly.

Lymphocyte Count before First Consolidation Therapy Is A Predictor of Relapse free Survival in Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of absolute lymphocyte count(ALC) before start of the first cycle of consolidation chemotherapy(CC) on the relapse free survival in the patients with acute myeloid leukemia(AML), so as to explore a simple and easy method for predicting AML relapse.</p><p><b>METHODS</b>The clinical data of 132 patients with newly diagnosed AML (all non-acute promyelotic leukemia) from 2011 to 2017 were analyzed retrospectively. The 132 AML patients were treated with standard induction chemotherapy (IC) and consolidation chemotherapy (CC). According to lymphocyte count of patients before start of the first cycle of CC, the AML patients were divided into 2 group: high lymphocyte count group (H-Lym≥1.2×10/L) and low lymphocyte count group (L-Lym<1.2×10/L). The differences in ralapse rate and relapse-free survival between 2 groups were analyzed.</p><p><b>RESULTS</b>Among 132 patients with AML, patients who could be valuated and were elicible for the study accounted for 65 (49.24%). The absolute leukocyte count, age, chromosome karyotypes before IC of patients did not show statistical difference between H-Lym group (40 cases) and L-Lym group (25 cases). Unvarvate analysis showed that the Low lymphocyte count and unfavorable chromosome karyotypes were poor prognostic factors for the relapse-free survival time, and there was significant difference between 2 groups (P<0.01). The relapse risk in patients of L-Lym group increased, the hazard ratio (HR)=3.01 (95% CI=1.55-4.98) (P<0.01). In multivariate analysis containing unfavorable prognostic karyotypes, this trend still existed (HR=2.52, 95% CI 1.28-9.98)(P<0.01).</p><p><b>CONCLUSION</b>The AML patients with high lymphocyte count before the first CC have more long relapse free survival time suggesting that the lymphocyte count before the first CC may be prognostic factor for relapse free survival of AML patients.</p>

The absolute value of lymphocyte counts and the response to decitabine treatment in patients with myelodysplastic syndrome / 解放军医学杂志

Objective To investigate the relations of absolute lymphocyte counts (ALC) to the therapeutic responses in patients with myelodysplastic syndrome (MDS) after the first course of decitabine (DAC) treatment.Methods Clinical data of 35 patients with MDS and MDS-derived secondary acute myeloid leukemia (AML) who were admitted in the Affiliated Hospital of Hebei University from Jan.2014 to Dec.2016 and treated with DAC were included in the present study.The patients were grouped into high lymphocyte group (H-Lym,ALC ≥ 1.2 × 109/L) and low lymphocyte group (L-Lym,ALC＜1.2 × 109/L) based on the ALC in days 28-35 after the first course of DAC treatment.The baseline data of both groups were compared with Pearson x2 analysis,while t test was used to analyze the changes of lymphocyte number before and after the first course of DAC treatment.Progressionfree survival (PFS) was estimated with Kaplan-Meier method,and the cumulative survival (CS) was compared between the two groups using log-rank test.Results Of the 35 patients,15 were in H-Lym group and 20 in L-Lym group.No significant difference existed in the baseline lymphocyte levels between the two groups (P＞0.05).The statistically significant differences (P＜0.05) existed only in the patients of the two groups who were with the proportion of bone marrow blasts ≥ 10％.The ALC in H-Lym group were slightly higher after the first course of DAC treatment than that at the time of diagnosis,but with no statistically significant (P＞0.05).However,the ALC in L-Lym group were significantly lower after the first course of DAC treatment than that at the time of diagnosis (P＜0.05).Patients had higher overall response rate (ORR) in H-Lym group than in L-Lym group (80％ vs.40％,P＜0.05).The median PFS was 10 months in H-Lym group and 7.6 months in L-Lym group (P＜0.05).Univariate analysis showed that the low ALC was a poor prognostic factor for the progression ofMDS (P＜0.05).Conclusion Patients with ALC ≥ 1.2 × 109/L after the first course of DAC treatment will have better ORR and longer PFS.

Predicting Therapeutic Response by Lymphocyte Level at 28th Day after DAC Treatment in Patients with MDS / 中国实验血液学杂志

OBJECTIVE@#To investigate a reliable clinical indication for predicting the therapeutic response of decitabine therapy in the patients with myelodysplastic syndromes (MDS).@*METHODS@#The clinical efficacy of decitabine for 55 cases of MDS was analyzed retrospectively. According to the lymphocyte level at d28 after the first time treatment with decitabine, the patients were divided into high lymphocyte level group (H-Lym≥1.2×10/L) and low lymphocyte level group (L-Lym<1.2×10/L), and the overall response rate (ORR) and the progression-free survival (PFS) time in 2 groups were compared.@*RESULTS@#As compared with L-Lym group, the ORR and PFS time in H-Lym group were significantly enhanced ［(76.0% vs 50.0%) (P<0.05) and median time (15.7 months vs 8.5 months)(P<0.05), respectively］;the ratio of platelet level ≥100×10/L in H-Lym group was very significantly higher than that in L-Lym group (72.0% vs 20.0%)(P<0.01). Multivariat analysis showed that the risk of disease progression in L-Lym group was 4.45-fold of H-Lym group (95% CI:1.58-12.59)(P<0.05).@*CONCLUSION@#The patients with lymphocyte level ≥1.2×10/L at day 28 after the first time treatment with decitabine show the higher ORR and longer PFS time, therefore. the lymphocyte level at day 28 after first time treatment with decitabine can be used as an early clinical indicator for predecting the response to decitabine treatment.

Efects of Inhibiting miR-155 Expression on the Proliferation and Apoptosis of Leukemia THP-1 Cells / 中国实验血液学杂志

The aim of this study was to investigate the effects of miR-155 inhibitor transfection on the proliferation and apoptosis of THP-1 cells. The miR-155 inhibitor was transfected into THP-1 cells (THP-1I) by using X-treme GENE siRNA transfection reagent. Cells without transfection (THP-1C) and cells with negative transfection (THP-1IC) were used as controls. Quantitative real-time polymerase chain reaction (RT-PCR) was performed to detect the expression of miR-155 and relative expression of SHIP1 mRNA in the cells. Cell proliferation was assayed using CCK-8 method. Cell apoptosis were detected by flow cytometry. The expression of SHIP1, TAKT and pAKT in THP-1 cells were detected by Western blot. The results indicated that compared with THP-1C and THP-1IC, the expression of miR-155 in THP-1I cells was significantly reduced; miR-155 inhibition significantly increased apoptosis rate in THP-1 cells (P < 0.05) ; miR-155 inhibition in THP-1 cells caused no significant alteration in SHIP1 mRNA level but significantly increased its protein content, indicating some post-transcriptional modulations might exist underlying the modulation of miR-155 to SHIP1, the miR-155 caused significantly reduced protein level of pAKT (P < 0.05) without interfering TAKT protein content. It is concluded that the miR-155 inhibition may promote THP-1 cell apoptosis through increasing SHIP1 protein content and impairing its downstream PI3K/AKT signaling pathway. This study suggests that miR-155 inhibition may be a promising therapy strategy for treating acute myeloid leukemia (AML).