Effect of modified FC/ATG preconditioning on allogeneic hematopoietic stem cell transplantation for severe aplastic anemia / 中华器官移植杂志

Objective:To evaluate the efficacy and safety of modified FC/ATG pretreatment in the treatment of severe aplastic anemia(SAA).Methods:From June 2012 to June 2020, clinical data of 64 patients with severe aplastic anemia undergoing allogeneic hematopoietic stem cell transplantation with modified FC/ATG(Flu 30 mg·m -2·d -l, -5~-2 d、CTX 50 mg·kg -1·d -1~-2 d、ATG: 2.5 mg·kg -1·d -1, -5~-2 d) pretreatment were retrospectively analyzed.There were MSD-HSCT ( n=29) and Haplo-HSCT ( n=35). Results:One patient died of intracerebral hemorrhage before transplantation and the remainders were completely implanted.During a median follow-up period of 14.5(1-95) months, overall survival (OS) rate of 92.2%.It was significantly higher than OS rate of 67.2% in the treatment of SAA by foreign pretreatment regimens containing low-dose TBI.And pretreatment scheme containing FC+ BU/TBI had an OS of slightly >91.3% in the treatment of SAA.The 3-year OS rates were 85.7% and 93.5% in Haplo-HSCT and MSD-HSCT groups ( P=0.058). The OS rate of SAA Haplo-HSCT/MSD-HSCT group was similar to that of " Beijing Protocol" (BU/CY+ ATG) (89%, 91%). The viral infection rates of EB and CMV were significantly higher in haplo-HSCT group than those in MSD-HSCT group and inter-group difference was statistically significant ( P<0.05). However, univariate analysis showed that two groups had no effect on survival time ( P=0.403, P=0.132). Univariate analysis showed that survival time was significantly associated with the presence of Ⅲ-Ⅳ° aGVHD and the presence of severe complications ( P=0.007, P=0.001). Further multivariate analysis revealed that severe complication was an independent risk factor for survival ( P=0.003). Conclusions:The efficacy of improved FC/ATG pretreatment in the treatment of SAA in MSD-HSCT or Haplo-HSCT is higher than other domestic and international pretreatment schemes in OS rate, safety and effectiveness.Onset of severe complication and association with Ⅲ ~ Ⅳ ° aGVHD are the influencing factors for patient survival.The efficacy of Haplo-HSCT group is similar to that of MSD-HSCT group.It may be employed as an alternative donor for SAA patients without fully congruent donors.

Analysis of gonad and reproductive function of recipients after hematopoietic stem cell transplantation in severe aplastic anemia / 中华器官移植杂志

Objective:To compare the effects of two pretreatment schemes on the efficacy, gonad and reproductive function of haploid hematopoietic stem cell transplantation recipients with severe aplastic anemia(SAA).Methods:The data of 73 patients with SAA who underwent haploid hematopoietic stem cell transplantation were analyzed retrospectively.The pretreatment scheme was divided into Fludarabine+ Cyclophosphamide+ Antithymocyte globulin group(FC lowATG group, 45 cases)and Busulfan+ Cyclophosphamide+ Antithymocyte globulin group(Bucy/ATG group, 28 cases). The changes of blood cell implantation time, follicle stimulating hormone(FSH), luteinizing hormone (LH), estradiol and testosterone were compared between the two groups. Results:there was no significant difference in blood cell implantation time between the two groups( P=0.096; P=0.133). The levels of FSH and LH in female recipients in Bucy/ATG group were higher than those in FC lowATG group, and the level of estradiol was lower than that in FC lowATG group.There were significant differences between the groups(all P<0.05). The pregnancy or fertility rate of female recipients in Bucy/ATG group was lower than that in FC lowATG group(all P<0.05). There was no significant difference in FSH, LH, testosterone and fertility between the two groups(all P>0.05). There was no significant difference in 2-year overall survival rate and failure free survival rate between the two groups( P=0.091; P=0.084). Conclusions:FC lowATG may be an effective pretreatment scheme for haploid hematopoietic stem cell transplantation in SAA with less damage to gonad and reproductive function.

Clinical analysis of sodium valproate combined with decitabine for treatment of myelodysplastic syndrome / 白血病·淋巴瘤

Objective To observe the clinical effects and safety of sodium valproate combined with decitabine for treatment of myelodysplastic syndrome (MDS). Methods Forty-two patients with MDS were enrolled in department of hematology in Shanxi Dayi Hospital from February 2012 to February 2017. According to random number table, the patients were divided into the control group (21 cases) and the experimental group (21 cases). The patients in the control group received decitabine at the dose of 20 mg·m-2·d-1, and intravenous infusion was completed in 2 hours, continuous therapy up to 5 days, 4 weeks as a course; the patients in the experimental group received combined medication, orally given sodium valproate 0.2 g once, 3 times per day. One week later, the dosage was added to 0.4 g once, 3 times per day. Both groups received at least 4 courses of treatment. The treatment was stopped when serious adverse reactions or obvious disease progression occurred. The bone marrow smear was rechecked every 4 weeks after treatment to evaluate the efficacy. The expressions of ASXL1, DNMT3A and TET2 in bone marrow cells were detected by fluorescence quantitative PCR before and after treatment. Results The total treatment response rate of the experimental group and the control group were 76.2 % (16/21) and 57.1 % (12/21) respectively, and there was statistically significant difference (P< 0.05); the total remission rate of the two groups was 47.6 % (10/21) and 38.1 %(8/21) respectively, and there was no significant difference (P> 0.05). All patients had slight adverse reactions, and the adverse reaction rate was 42.9 % (9/21) and 38.1 % (8/21), and there was no significant difference (P>0.05). The content of TET2 mRNA and DNMT3A mRNA after treatment in both groups were decreased compared with the expressions before treatment, and there were significant differences (P<0.05). However, there was no significant difference between the two groups after treatment (P> 0.05); the content of ASXL1 mRNA had no obvious change in the control group and a dramatic decrease in the experimental group compared with that before treatment (P<0.05). Conclusion Sodium valproate combined with decitabine has favorable effects and mild adverse reactions for treatment of MDS, besides, it can influence the expressions of TET2, DNMT3A and ASXL1.

The comparative study of the effects between modified FLAG and CAG on relapsed or refractory acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and toxicity of modified FLAG and CAG on relapsed or refractory acute myeloid leukemia (AML).</p><p><b>METHODS</b>Sixty-one patients with relapsed or refractory AML were divided into modified FLAG or CAG group. In modified FLAG group: G-CSF 200 μg·m⁻²·d⁻¹ on days 0-5; fludarabine 30 mg·m⁻²·d⁻¹ on days 1-5; Ara-C 1.0 g·m⁻²·d⁻¹ on days 1-5. In CAG group: Ara-C 10 mg·m⁻²·12 h⁻¹ on days 1-14, aclarubicin 20 mg/d on days 1-4, G-CSF 200 μg·m⁻²·d⁻¹ on days 0 1-14.</p><p><b>RESULTS</b>The complete response (CR) rate was 43% (12/28) and the partial response (PR) rate 18% (5/28) with the overall response (OR) rate of 61% in modified FLAG group. CR rate was 21% (7/33) and PR rate 15% (5/33) with OR rate of 36% in CAG group. There was significant statistical difference between two groups (P<0.05). The main toxicities of these groups were myelosupression and infection. The infection rate was 68% (19/28) in modified FLAG group (twenty-two patients were treated in the sterile laminar flow ward duing neutropenic period), treatment related mortality (TRM) in modified FLAG group was 7%; The infection rate was 55% (18/33) in CAG group (no patient was treated in the sterile laminar flow ward), TRM in CAG group was 3%. There was no significant statistical difference in two groups (P>0.05).</p><p><b>CONCLUSION</b>Modified FLAG was effective for relapsed or refractory AML. The supportive cares to strengthen infection-controlled measures and shorten the period of bone marrow suppression produced the additional effect. CAG regimen has low adverse reactions and could be individualized to elder or weak patients.</p>

Detection of the effect of bortezomib with arsenic trioxide different concentration on the cell cycle and apoptosis of Raji cells by flow cytometry / 白血病·淋巴瘤

Objective To investigate the effect of bortezomib with arsenic trioxide different concentration on the cell cycle and apoptosis of Raji cells. Methods Flow cytometry analysis showed that the relative number of cells in different phases and the percentages of cells calculated in G1 and S phase of the cell cycle and apoptosis were assessed after treatment with As2O3 and BOR or in combination with BOR in different concentration at indicated time (24 h, 48 h, 72 h). Results Flow cytometric analysis showed that the cell cycle was arrested at G1 phase, the number of cells G1 period increased significantly, and S phase decreased on Raji cells after As2O3 treatment. The relationship between the cellular DNA contents and the concentration of As2O3 showed a dose-and time-dependent manner (P ＜0.0001). But it was found that BOR had no effect on Raji cell cycle, but, in two drugs combination, cell apoptosis rate significantly increased from 16.98 % to 45.84 %. Conclusion The results show that As2O3 exerted variable and definite effects on lymphoma Raji cells, which indicated that As2O3 might induce apoptosis and arrest cell cycle. The combination of two drugs had a effective and synergistic effect on apoptosis.